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1 . Jason Jerald, The VR Book: Human-Centered Design for Virtual Reality (ACM Books), 2015

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1 . Jason Jerald, The VR Book: Human-Centered Design for Virtual Reality (ACM Books), 2015

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2. Peter Rubin, Future Presence: How Virtual Reality Is Changing Human Connection, Intimacy, and the Limits of Ordinary Life, 2018

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2. Peter Rubin, Future Presence: How Virtual Reality Is Changing Human Connection, Intimacy, and the Limits of Ordinary Life, 2018

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3. Bucher, John K., Storytelling for virtual reality : methods and principles for crafting immersive narratives, 2018

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3. Bucher, John K., Storytelling for virtual reality : methods and principles for crafting immersive narratives, 2018

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4. Chalmers, David John, Reality+ : virtual worlds and the problem of philosophy, 2022

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4. Chalmers, David John, Reality+ : virtual worlds and the problem of philosophy, 2022

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5. Jeremy Bailenson, Experience on demand. What Virtual Reality is, how it works, and what it can do, 2018

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5. Jeremy Bailenson, Experience on demand. What Virtual Reality is, how it works, and what it can do, 2018

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Application of Virtual Reality Technology in Clinical Practice, Teaching, and Research in Complementary and Alternative Medicine, 2022

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Application of Virtual Reality Technology in Clinical Practice, Teaching, and Research in Complementary and Alternative Medicine, 2022

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https://www.researchgate.net/publication/362654689_Application_of_Virtual_Reality_Technology_in_Clinical_Practice_Teaching_and_Research_in_Complementary_and_Alternative_Medicine

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The effect of Virtual Reality on evoked potentials following painful electrical stimuli and subjective, 2020

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The effect of Virtual Reality on evoked potentials following painful electrical stimuli and subjective, 2020

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https://www.researchgate.net/publication/341887065_The_effect_of_Virtual_Reality_on_evoked_potentials_following_painful_electrical_stimuli_and_subjective_pain

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Guided relaxation-based virtual reality versus distraction-based virtual reality or passive control for postoperative pain management in children and adolescents undergoing Nuss repair of pectus excavatum: Protocol for a prospective, randomised, controlled trial (FOREVR Peds trial), 2020

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Guided relaxation-based virtual reality versus distraction-based virtual reality or passive control for postoperative pain management in children and adolescents undergoing Nuss repair of pectus excavatum: Protocol for a prospective, randomised, controlled trial (FOREVR Peds trial), 2020

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https://www.researchgate.net/publication/348082986_Guided_relaxation-based_virtual_reality_versus_distraction-based_virtual_reality_or_passive_control_for_postoperative_pain_management_in_children_and_adolescents_undergoing_Nuss_repair_of_pectus_excav

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www.researchgate.net needs to review the security of your connection before proceeding.

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Evidence-Based Nonpharmacologic Strategies for Comprehensive Pain Care: The Consortium Pain Task Force White Paper

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Evidence-Based Nonpharmacologic Strategies for Comprehensive Pain Care: The Consortium Pain Task Force White Paper

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https://www.researchgate.net/publication/323502668_Evidence-Based_Nonpharmacologic_Strategies_for_Comprehensive_Pain_Care_The_Consortium_Pain_Task_Force_White_Paper

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Ready Patient One: The role of therapeutic virtual reality in the future management of chronic pain, 2022

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Ready Patient One: The role of therapeutic virtual reality in the future management of chronic pain, 2022

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https://www.researchgate.net/publication/353543297_Ready_Patient_One_the_role_of_therapeutic_virtual_reality_in_the_future_management_of_chronic_pain

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6. Jay David Bolter, Maria Engberg, Blair Maclntyre, Reality Media. Augmented and Virtual Reality, 2021

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6. Jay David Bolter, Maria Engberg, Blair Maclntyre, Reality Media. Augmented and Virtual Reality, 2021

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What Does Bleeding Edge Mean?

Bleeding edge refers to technology that has been released but is still not ready for the general public due to the fact that it has not been reliably tested. Bleeding edge technology is released in beta to early adopters in order to smooth out compatibility issues, user interface problems and other underlying design flaws and bugs that slipped through early testing.

Techopedia Explains Bleeding Edge

Bleeding edge is part pun and part ranking of the readiness of the technology for market. Bleeding edge technology is on its way to becoming cutting edge technology, after which it becomes leading edge as more companies release competing products. Finally, the technology becomes standard and everyone is on the look for the next big thing.

The term bleeding edge is sometimes applied to officially released technology that experiences problems soon after it becomes widely available. However, the term is more properly applied to the release of beta versions to early adopters for testing purposes. Early adopters of bleeding edge technology are highly valued by companies because they allow unfinished products to be refined much more quickly once a working version is ready.

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What is Bleeding Edge? - Definition from Techopedia

# data[].attributes.attachment_link.description
Bleeding edge refers to technology that has been released but is still not ready for the general public due to the fact that it has not been reliably tested. Bleeding edge technology is released in beta to early adopters in order to smooth out compatibility issues, user interface problems and other underlying design flaws and bugs that slipped through early testing.

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Ms Hardacre, the head of midwifery for Cardiff and Vale health board, said: "It provides us with an opportunity to do something really different, something innovative, something that's not being used elsewhere.

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Women in labour given virtual reality to ease pain of childbirth

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Ms Hardacre, the head of midwifery for Cardiff and Vale health board, said: "It provides us with an opportunity to do something really different, something innovative, something that's not being used elsewhere.

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Can Virtual Reality Replace Opioids As Pain Treatment?

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VR helps children's hospital patients escape pain and anxiety

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Virtual reality for pain and anxiety management in children

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Virtual reality for pain and anxiety management in children

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Abstract

Question Pain and anxiety are common in children who need procedures such as administering vaccines or drawing blood. Recent reports have described the use of virtual reality (VR) as a method of distraction during such procedures. How does VR work in reducing pain and anxiety in pediatric patients and what are the potential uses for it?

Answer Recent studies explored using VR with pediatric patients undergoing procedures ranging from vaccinations and intravenous injections to laceration repair and dressing changes for burn wounds. Interacting with immersive VR might divert attention, leading to a slower response to incoming pain signals. Preliminary results have shown that VR is effective, either alone or in combination with standard care, in reducing the pain and anxiety patients experience compared with standard care or other distraction methods.

Virtual reality (VR) is a computer technology that creates an artificial 3-dimensional simulated environment. Virtual reality consists of a head-mounted display and a thick pair of goggles that are connected to either a computer or a cell phone. The headset has sensors that track users' head movements, creating the illusion of moving around in the virtual space. In the past 15 years, the technology, accessibility, and widespread application of VR have progressed immensely. Virtual reality technology places patients into a "virtual world," such as the underwater world in Aqua,1 through audio and visual immersion, and encourages users to interact with this world.2 Although originally designed for entertainment purposes, the potential use of VR in the medical field has recently been explored. Experimental trials using VR in therapy for anxiety or posttraumatic stress disorder and for coping with pain demonstrate potential for this technology.3

Pediatric pain and anxiety management using VR technology

Pain is a complex experience comprising sensory, cognitive, behavioural, and psychological components. Painful procedures, such as vaccinations, intravenous injections, laceration repairs, and dressing changes for burn wounds are a common part of pediatric medical treatments.3 Painful situations during these procedures often lead to anxiety for patients, which can cause fear and greatly affect compliance with care for future procedures. Further, conditions causing chronic pain, such as sickle cell disease, might also have detrimental effects on the lives of children.

Common pediatric pharmacologic analgesia includes opioid therapy, which is known to have high tolerance and dependence.4 Opioids also have an unfavourable safety profile in children, with side effects ranging from nausea and constipation to cognitive impairment and respiratory depression.5

Distraction is a common nonpharmacologic technique used by health care professionals to manage and attenuate anxiety, and possibly pain, during painful procedures in pediatric patients.6 Both passive distraction (eg, watching television, listening to a book) and active distraction (eg, interactive toys, electronic games) have been extensively studied and cause a decrease in pain and anxiety.6 Virtual reality might offer even more distraction, as it completely immerses the patient in another world and involves multiple senses.7 Patients can actively or passively participate in numerous potential programs ( Table 1 ).4,5,8-14

How VR affects pain

The theory behind VR's role in reducing pain and not only anxiety is related to the limited attentional capacity humans have. Pain requires attention, and if some of that attention can be diverted (eg, by interacting with VR), the patient will have a slower response to incoming pain signals.8 Pain is detected by nociceptors located throughout the body that relay pain signals to the central nervous system via A-δ fibres and C-fibres.15 Many analgesics work by interrupting the C-fibre pathway, thus disrupting the way humans sense pain. Virtual reality does not interrupt the pain signals but acts both directly and indirectly on pain perception and signaling through attention, emotion, concentration, memory, and other senses.15

A study using functional magnetic resonance imaging of healthy patients who were using VR while exposed to a painful stimulus (thermal pain stimulator on the foot) showed a greater than 50% reduction in pain-related brain activity in 5 areas of the brain.16 A study of 9 subjects, aged 20 to 38, compared VR simulation to opioid analgesics during thermal pain stimulation, and results were measured with subjective pain reports and functional magnetic resonance imaging.9 Virtual reality and opioid analgesics had very comparable results in terms of pain reduction, and it was found that the combination of opioids with VR resulted in significant further reduction in pain signals ( P < .01).9

Applications for pain management

Studies looking at the value of VR show reductions in both acute and chronic pain in children.6 While the magnitude of pain from vaccines is not large, it is not uncommon for parents to postpone injections for their children owing to concerns about discomfort.17 Among 244 children 2 to 16 years of age from California receiving seasonal influenza vaccination, using VR for approximately 30 seconds before, during, and after vaccination was associated with a 45% to 74% decrease in pain experienced compared with usual care.18 This was evaluated by a questionnaire filled out by the children, parents, and staff immediately after the vaccination was given, which assessed fear, pain, desire to use VR in the future, VR relaxation, and staff ease in administering the vaccine.19

Acute dressing of burns8,20 and rehabilitation procedures10 are painful but important to prevent infections, contractures, and decreased range of motion in burn victims. Hoffman and colleagues incorporated VR and video games in the standard treatment of patients with burns.5,8,10,21 Eleven burn patients, who were between 9 and 40 years of age and who required inpatient hospitalization, reported a 35% to 50% decrease in perceived pain when using VR with standard pharmacologic treatment compared with pharmacologic treatment alone.5 This was assessed by subjects reporting 3 subjective pain ratings (cognitive, affective, and sensory) on a graphic rating scale (GRS) ranging from 0 to 10, followed by 4 subjective assessment questions related to how much fun they experienced and the "realness" of the VR (also measured using GRSs ranging from 0 to 10).5 A larger study performed with 54 children aged 6 to 19 years old who were undergoing physical therapy in the same hospital burn unit reported significant decreases in perceived pain (27% to 44%, P < .05) as well as increased affect ("fun") ( P < .001).10 These results were measured using GRS tools ranging from 0 to 100 for the same questions and provide hope that these patients will have increased compliance with treatment, which would lead to improved long-term outcomes.10

A research group at Benioff Children's Hospital in San Francisco, Calif, developed VR software for children with sickle cell acute pain crises (vaso-occlusive crises).12 Among 25 children and young adults 10 to 25 years of age, there was a 16% reduction in pain intensity and a 33% reduction in pain descriptors, measured using the Adolescent Pediatric Pain Tool.13

A study by Gershon et al was conducted in patients with childhood cancer (leukemia, lymphoma, solid mass) receiving port access as part of their oncology treatment at an outpatient oncology unit. Fifty-nine children 7 to 19 years of age were divided into 3 groups: a control group that received standard treatment (topical anesthetic cream), a group that received non-VR distraction, and a group that received VR distraction.11 The children's levels of anxiety and pain were noted to decrease while using VR through 3 different assessments. Pain was reported by the patients, parents, and nurses using a visual analogue scale; pain was reported by the researchers using the Children's Hospital of Eastern Ontario Pain Scale, and they also measured the change in pulse rate during placement of the subcutaneous venous port device.11

Conclusion

Recent technological advances have led to considerable cost reductions for VR equipment, and several companies are selling headsets that consist of 2 lenses and a place to insert a smartphone for less than $20.3 This has opened the door to using VR in a clinical setting, and further research will likely solidify the efficacy of VR in pain reduction in a range of medical situations.

Notes

PRETx Pediatric Research in Emergency Therapeutics

Child Health Update is produced by the Pediatric Research in Emergency Therapeutics (PRETx) program (www.pretx.org) at the BC Children's Hospital in Vancouver, BC. Ms Arane and Dr Behboudi are members and Dr Goldman is Director of the PRETx program. The mission of the PRETx program is to promote child health through evidence-based research in therapeutics in pediatric emergency medicine.

Do you have questions about the effects of drugs, chemicals, radiation, or infections in children? We invite you to submit them to the PRETx program by fax at 604 875-2414; they will be addressed in future Child Health Updates. Published Child Health Updates are available on the Canadian Family Physician website (www.cfp.ca).

Footnotes

This article is eligible for Mainpro+ certified Self-Learning credits. To earn credits, go to www.cfp.ca and click on the Mainpro+ link.

Cet article se trouve aussi en français à la page 935.
Competing interests
None declared

References

2. Lange B, Williams M, Fulton I. Virtual reality distraction during pediatric medical procedures. Pediatr Pain Lett. 2006;8(12):6-10. [ Google Scholar]

13. Robertson S. Virtual reality as a complementary therapy to improve pain in sickle cell disease. Paper presented at: Academy for Sickle Cell and Thalassaemia Conference; 2016 Oct 5; London, Engl. [ Google Scholar]

14. Lagnado L. A virtual approach to real pain. The Wall Street Journal. 2017 Jul 13;:A9. [ Google Scholar]

19. Silverberg Z, Silverberg M, La Puma J. Virtual reality and vaccination: see the sea and be pain-free?. Paper presented at: World Summit on Pediatrics; 2017 Jun 24; Rome, Italy. [ Google Scholar]

Articles from Canadian Family Physician are provided here courtesy of College of Family Physicians of Canada

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Virtual reality for pain and anxiety management in children

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Question Pain and anxiety are common in children who need procedures such as administering vaccines or drawing blood. Recent reports have described the use of virtual reality (VR) as a method of distraction during such procedures. How does VR work in ...

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https://www.nhs.uk/conditions/complementary-and-alternative-medicine/

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Defining CAMs

There's no universally agreed definition of CAMs.

Although "complementary and alternative" is often used as a single category, it can be useful to make a distinction between the 2 terms.

The US National Center for Complementary and Integrative Health (NCCIH) uses this distinction:

When a non-mainstream practice is used together with conventional medicine, it's considered "complementary".

When a non-mainstream practice is used instead of conventional medicine, it's considered "alternative".

There can be overlap between these categories.

For example, aromatherapy may sometimes be used as a complementary treatment, and in other circumstances is used as an alternative treatment.

A number of complementary and alternative treatments are typically used with the intention of treating or curing a health condition.

Examples include:

Deciding to use complementary or alternative treatments

To understand whether a treatment is safe and effective, we need to check the evidence.

You can learn more about the evidence for particular CAMs by reading about individual types of treatment.

See our index for a list of all conditions and treatments covered by the NHS website.

Some complementary and alternative medicines or treatments are based on principles and an evidence base that are not recognised by the majority of independent scientists.

Others have been proven to work for a limited number of health conditions.

For example, there's evidence that osteopathy and chiropractic practices are effective for treating lower back pain.

When a person uses any health treatment, including a CAM, and experiences an improvement, this may be due to the placebo effect.

Finding a CAM practitioner

If you think you may have a health condition, first see your GP. Do not visit a CAM practitioner instead of seeing your GP.

It's particularly important to talk to your GP if you have a pre-existing health condition or are pregnant.

Some CAMs may interact with medicines that you're taking or should not be taken if you're pregnant.

CAMs and regulation

The practice of conventional medicine is regulated by laws that ensure that practitioners are properly qualified and adhere to certain standards or codes of practice. This is called statutory professional regulation.

Professionals of 2 complementary and alternative treatments - osteopathy and chiropractic - are regulated in the same way.

There's no statutory professional regulation of any other CAM practitioners.

Finding an osteopath or chiropractor

Osteopathy and chiropractic are regulated in the same way as conventional medicine.

All osteopaths must be registered with the General Osteopathic Council. You can use the General Osteopathic Council website to find a registered osteopath near you or check if someone offering osteopathic services is registered.

All chiropractors must be registered with the General Chiropractic Council. You can use the General Chiropractic Council website to find a registered chiropractor near you or check if someone offering chiropractic services is registered.

Finding other CAM practitioners

Apart from osteopathy and chiropractic, there's no professional statutory regulation of complementary and alternative treatments in the UK.

This means:

it's legal for anyone to practise the treatment, even if they have no or limited formal qualifications or experience

these practitioners are not legally required to adhere to any standards of practice or to join an association or register

If you decide to use a CAM, it's up to you to find a practitioner who will carry out the treatment in a way that's acceptable to you. Professional bodies and voluntary registers can help you do this.

Some regulated healthcare professionals, such as GPs, also practise unregulated CAMs.

In these instances, the CAM practice is not regulated by the organisation that regulates the healthcare professional (such as the General Medical Council), but these organisations will investigate complaints that relate to the professional conduct of their member.

Professional associations and accredited registers for CAMs

Many CAMs have voluntary registers (some of which are accredited by the Professional Standards Authority for Health and Social Care, or the PSA) or professional associations that practitioners can join if they choose.

Usually, these associations or registers demand that practitioners hold certain qualifications and agree to practise to a certain standard.

Organisations with PSA-accredited voluntary registers include:

This means that these organisations have met the PSA's demanding standards, which are designed to help people make an informed choice when they're looking for a practitioner.
Find more information on the PSA's accredited registers
Questions to ask before starting a treatment

Once you have found a practitioner, it's a good idea to ask them some questions to help you decide if you want to go ahead with treatment.

You could ask:

about the cost of treatment

how long the treatment will last

whether there are any people who should not use this treatment

what side effects the treatment might cause

whether there's anything you should do to prepare for treatment

what system the practitioner has for dealing with complaints about their treatment or service

for documentary proof of their qualifications

for documentary proof that they're a member of their professional association or voluntary register

for documentary proof that they're insured

for written references

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There's no universally agreed definition of CAMs. Although "complementary and alternative" is often used as a single category, it can be useful to make a distinction between the 2 terms. The US National Center for Complementary and Integrative Health (NCCIH) uses this distinction: When a non-mainstream practice is used together with conventional medicine, it's considered "complementary".

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Virtual Reality Analgesia With Interactive Eye Tracking During Brief Thermal Pain Stimuli: A Randomized Controlled Trial (Crossover Design)

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Virtual Reality Analgesia With Interactive Eye Tracking During Brief Thermal Pain Stimuli: A Randomized Controlled Trial (Crossover Design)

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990370/

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Najood A. Al-Ghamdi, ¹ Walter J. Meyer, III, 2, ³ Barbara Atzori, ⁴ Wadee Alhalabi, 5, 6, ⁷ Clayton C. Seibel, ⁸ David Ullman, ⁸ and Hunter G. Hoffman 8, 9,*

Abstract

In light of growing concerns about opioid analgesics, developing new non-pharmacologic pain control techniques has become a high priority. Adjunctive virtual reality can help reduce acute pain during painful medical procedures. However, for some especially painful medical procedures such as burn wound cleaning, clinical researchers recommend that more distracting versions of virtual reality are needed, to further amplify the potency of virtual reality analgesia. The current study with healthy volunteers explores for the first time whether interacting with virtual objects in Virtual Reality (VR) via "hands free" eye-tracking technology integrated into the VR helmet makes VR more effective/powerful than non-interactive/passive VR (no eye-tracking) for reducing pain during brief thermal pain stimuli.

Method

Forty eight healthy volunteers participated in the main study. Using a within-subject design, each participant received one brief thermal pain stimulus during interactive eye tracked virtual reality, and each participant received another thermal pain stimulus during non-interactive VR (treatment order randomized). After each pain stimulus, participants provided subjective 0-10 ratings of cognitive, sensory and affective components of pain, and rated the amount of fun they had during the pain stimulus.

Results

As predicted, interactive eye tracking increased the analgesic effectiveness of immersive virtual reality. Compared to the passive non-interactive VR condition, during the interactive eye tracked VR condition, participants reported significant reductions in worst pain ( p < 0.001) and pain unpleasantness ( p < 0.001). Participants reported a significantly stronger illusion of presence ( p < 0.001), and significantly more fun in VR ( p < 0.001) during the interactive condition compared to during passive VR. In summary, as predicted by our primary hypothesis, in the current laboratory acute pain analog study with healthy volunteers, increasing the immersiveness of the VR system via interactive eye tracking significantly increased how effectively VR reduced worst pain during a brief thermal pain stimulus. Although attention was not directly measured, the pattern of pain ratings, presence ratings, and fun ratings are consistent with an attentional mechanism for how VR reduces pain. Whether the current results generalize to clinical patient populations is another important topic for future research. Additional research and development is recommended.

Keywords: virtual reality, analgesia, pain, distraction, non-pharmacologic analgesic techniques, opioid analgesia

Introduction

Excessive pain during medical procedures is a frequent problem, worldwide, and recovering from a severe burn is often unusually painful. As part of the natural healing process, severe burns exfoliate dead skin cells. To prevent infection and speed up healing, wound care nurses remove the bandages, and wipe/scrub the burn wound with a wet washcloth to remove/clean off the thin layer of sloughed off dead skin cells, and other debris.

Despite giving patients powerful analgesia pain medications shortly before wound care, patients typically remain conscious during burn wound care, pain during non-surgical wound debridement of severe burn wounds is often severe to excruciating, and wound care procedures are repeated frequently. Children with large burns typically have their burn wounds cleaned several days per week, during several weeks of hospitalization ( Hoffman et al., 2019).

Psychological factors such as fear, anxiety and depression can increase or amplify how much pain patients subjectively experience during painful medical procedures ( Hemington et al., 2017), making pain management even more challenging. What people are thinking about, and where patients direct their attention during medical procedures ( Heathcote et al., 2017), expectations of pain, and memories of previous painful procedures can increase pain intensity ( Melzack and Wall, 1965; Noel et al., 2012, 2015a, b; Fields, 2018; Fischer et al., 2018).

Opioid analgesics are widely regarded as effective and essential tools for acute pain management such as burn wound care ( Malchow and Black, 2008; McIntyre et al., 2016; Ballantyne, 2018) but opioid side effects such as nausea, constipation, urinary retention, drowsiness, and lack of appetite ( Mendez-Romero et al., 2018) limit opioid dose levels ( Cherny et al., 2001). In addition, there are growing concerns about over-prescription of opioids in the United States and Europe ( Krane, 2019; Yaster et al., 2019). There are also growing concerns about the opposite problem of limited availability of opioids in under-developed countries ( Vijayan, 2011), recent shortages of medical opioid analgesics in the United States, and possible large reductions in availability in the future, in light of stricter laws and large lawsuits against pharmaceutical companies that sell opioid analgesics. In light of growing problems with opioid analgesics, developing effective new non-pharmacologic pain control treatments has become a national and international priority ( Keefe et al., 2012, 2018).

Psychological pain control techniques can help reduce reliance on opioids, and may help compensate for undermedication. There is growing evidence that adjunctive immersive virtual reality distraction can help reduce the suffering of patients during medical procedures with little or no side effects from the VR ( Hoffman, 1998; Hoffman et al., 2000, 2011; Garrett et al., 2014; Atzori et al., 2018a, b; Indovina et al., 2018). Virtual reality goggles with eye tracking technology embedded into the goggles, have recently become commercially available, and could potentially help make VR more distracting. However, to date, one important gap in the scientific VR analgesia literature is that there have been no PubMed indexed studies using eye tracked Virtual Reality to treat pain.

In previous clinical studies, virtual reality has typically been used in addition to traditional pain medications to help reduce the pain experienced by patients during painful severe burn wound cleaning sessions ( Hoffman et al., 2000, 2004a, 2019; Maani et al., 2011a, b; Kipping et al., 2012; Faber et al., 2013; Jeffs et al., 2014; Khadra et al., 2018; McSherry et al., 2018)1. In a military study, while in virtual reality, soldiers with combat-related burn injuries spent less time thinking about their pain, patients reported reductions in worst pain intensity and reductions in the emotional component of pain (pain unpleasantness) during VR, and patients reported having more fun when they went into virtual reality during medical procedures, compared to standard of care pain medications alone ( Maani et al., 2008, 2011a, b).

The essence of immersive virtual reality analgesia is the patient's illusion of going to a different place, the subjective experience of "feeling present" in the computer generated world, as if the virtual world is a place the patient is visiting ( Slater et al., 1994; Slater and Wilbur, 1997). Researchers argue that the illusion of "being there" in virtual reality is unusually attention grabbing ( Hoffman et al., 2000, 2001, 2003b, 2004a, 2004b, 2004c, 2007; Law et al., 2011). For example, people perform more poorly on a divided attention task while in virtual reality ( Hoffman et al., 2003b). The perception of pain requires attentional resources. Researchers (e.g., Hoffman, 1998; Hoffman et al., 2000; Birnie et al., 2017), propose that VR uses up so much attention, that the patient's brain has less attention available to process incoming nociceptive signals traveling from the burn wound to the brain while the wound is being cleaned.

One clinical research study recently explored the use of virtual reality to help reduce the pain of pediatric patients with large severe burn injuries during burn wound cleaning sessions in the intensive care unit of a regional pediatric burn center ( Hoffman et al., 2019). Although patients reported large and significant reductions in pain during burn wound care, the researchers recommended that stronger versions of virtual reality need to be developed, in order to better distract patients experiencing such high levels of pain during burn wound cleaning.

Researchers have described and tested design guidelines for how to make VR more effective. Several analog laboratory thermal pain studies have shown that more immersive VR systems designed to elicit a stronger illusion of feeling present in the virtual world are more effective at reducing pain ( Hoffman et al., 2004c, 2006, 2014; Dahlquist et al., 2007; Wender et al., 2009; Law et al., 2011; Zeroth et al., 2019). Interacting with the virtual world increases the immersiveness of the VR system, potentially increasing the amount of attention drawn into the virtual world (e.g., Wender et al., 2009). The results of these laboratory studies have helped guide the design of effective VR analgesia systems, e.g., fMRI magnet-friendly wide field of view VR helmets, e.g., Hoffman et al. (2004b, 2007) and the development robot-like arm VR goggle holders for severe burn patients ( Maani et al., 2008, 2011a, b; Hoffman et al., 2019).

Unfortunately, increasing the immersiveness of VR systems used in the ICU for children with large severe burn injuries is both highly recommended, but also technically challenging. Burns on their heads and face often preclude burn patients from wearing a traditional VR helmet, so head tracking is not possible. Children with large severe burn injuries also often have severe burns on their hands/fingers, making it difficult for them to use mouse tracking to interact with the virtual world during burn wound care.

In the current pilot laboratory study, we used a new VR helmet that allows participants to use their eye movements as a "hands free" input device to interact with the virtual world. We predicted that adding interactivity via an eye tracking system embedded into the VR goggles would increase the immersiveness of the VR system, and would increase the participants illusion of "being there" in the virtual world, making VR more attention grabbing and more effective at reducing the acute pain of healthy volunteers during brief thermal pain stimuli. Several large computer companies are developing and marketing new virtual reality and augmented reality eye tracking technologies. https://www.forbes.com/sites/solrogers/2019/02/05/seven-reasons-why-eye-tracking-will-fundamentally-change-vr/#16bfb2c83459. For example, Apple Computers recently purchased SMI. Note that SMI is the company that made the eye tracking technology used in the current study.

The current analog laboratory pain study with healthy volunteer participants is the first controlled study in the PubMed literature to explore whether interactive eye tracking can enhance the analgesic effectiveness of virtual reality distraction. The SMI eye tracked HTC VIVE VR helmet starts with a standard HTC VIVE helmet. But in addition, each eyepiece of the goggles is trimmed with a small ring of eye tracking technology2. Six infrared lights are positioned in a circle around each eye. In addition to the low energy infrared lights, miniature infrared cameras mounted onto the same ring record the pattern of red lights with an infrared camera (see Figure 3 ). These miniature cameras can make real time digital video streams of the six small red dots of infrared light reflected off of the outer surface of the patient's eyes (the cornea). As the participants look at different objects in the computer generated world, the pattern of infrared dots changes shape. The VR computer can tell from the pattern of dots, where the patient is looking (search www.youtube.com for "SMI eyetracked virtual reality" for related informational videos). Because the eye tracking system only uses light in the narrow bandwidth of infra-red, the video camera is able to ignore confusing reflection noise from the visible spectrum and infrared thus improves eye tracking accuracy.

The information from the miniature infrared cameras mounted in the VR helmet is transmitted to the VR software program in the VR computer. In the current study, participants interact with the virtual world by aiming virtual snowballs at virtual objects in the 3D virtual canyon. Just as a computer mouse input device can be used to move a computer cursor around a computer screen, using eye tracking technology embedded into the VR goggles, in the current study, the participant in virtual reality can aim snowballs at objects in virtual reality by simply looking at the virtual objects. Essentially, the "cursor" or reticle crosshair, follows the patient's eye fixations. So if the patient looks at a Snowman in virtual reality, the virtual snowballs hit the Snowman, and the virtual snowman reacts (with special animated effects) when hit by a snowball.

The current laboratory thermal pain study with healthy volunteers explores for the first time, whether interactive eye tracking can enhance the analgesic effectiveness of virtual reality distraction.

Materials and Methods

Subjects

Forty-eight female college student volunteers from Effat University (age range 18-30 years old, mean = 21.77, SD = 2.07) participated in the main study, and an additional 24 students (from the identical context as the main study participants) were randomized to participate in a small pilot side study, to test our pain paradigm assumption that pain ratings were stable over repeated stimulations for people who received two test pain stimuli with No VR. Effat University is an all female institution of higher education for women in Jeddah Saudi Arabia. All data was collected by female research assistants and all participants were female, an understudied gender. This research was conducted in accordance with the Declaration of the World Medical Association3. All subjects gave written informed consent in accordance with the Declaration of Helsinki. Both written and verbal informed consent were obtained using a protocol approved by the Effat University's Human Subjects Review Committee.

Within-Subjects Design

Each of the 48 participants who received VR rated their pain during "eye tracked VR" during one thermal pain stimulus (e.g., Test 1), and rated their pain again during a second thermal stimulus during "passive VR" (e.g., Test 2). Treatment order of passive VR vs. interactive eye tracked VR was randomized using random number sequences from www.random.org. Some people received "eye tracked VR" first and "passive VR" second, and some people received "passive VR" first and "eye tracked VR" second. Each individual participant's pain during passive VR was compared to that same participant's pain during interactive eye tracked VR.

Measures and Procedures

Experimental Thermal Pain Model

Controlled thermal pain stimulation was applied using a commercially available computerized Medoc thermal pain stimulator4 (Medoc Q-Sense Ramp and Hold program). During the first phase of the study, each participant selected the temperature they would use in this study. The stimulus temperature (range = 44 - 48.5°C in the present study) of each 10 s heat stimulus temperature was individually determined for each subject using the psychophysical method of ascending levels ( Hoffman et al., 2004b, 2007). A 10-s heat stimulus (always 44°C for the first stimulus) was delivered via a thermode attached to the participant's forearm (by a female researcher), and the subject was asked to rate their pain during the stimulus using a 0-10 graphic rating scale. With the subject's permission, the temperature for the next stimulus was then increased by 1°C (or less, if the participant was approaching their maximum) and participants again rated their pain. This sequence was repeated until the subject reported a stimulus that was "painful but tolerable" for the brief stimulus duration, and that the subject was willing to receive for two additional 10-s thermal pain stimuli. This final stimulus temperature that the participant selected for the baseline pain condition (10-s thermal stimulus with no distraction) also served as the pain stimulus temperature used during the subsequent VR interventions (10 s of thermal pain during passive VR distraction, and 10 s of thermal pain during interactive eye-tracked VR, VR treatment order randomized). Allowing participants to select the temperature they would use in this experiment was popular with the participants.

The VR system was carried out using a gaming laptop: MSI GeForce GTX 1080 8 GB, Intel Core i7 7th (2.80 GHz), 16 GB RAM, Windows 10 operating system connected to an SMI HTC VIVE VR helmet with FOV 110° from HTC, with 1080 × 1200 pixels per eye resolution and a refresh rate of 90 Hz. The head mounted display VR helmet, integrated with SMI eye-tracking 250 Hz, works with the SDK C + + \C# for various VR engines like Unity. A new VR world, SnowCanyon5,6 was integrated with the eye tracking hardware, enabling participants to use the eye-tracker to select a virtual object by simply looking at the virtual object target (e.g., a virtual snowman) in the VR goggles. The SnowCanyon virtual environment5 presents a virtual arctic canyon to the user, complete with flowing river below, blue sky above, and terraced canyon walls to the sides containing virtual penguins, igloos, and snowmen (see Figure 1 ). Subjects in both treatment conditions wore an HTC VIVE VR helmet head-mounted display with an integrated SMI eye tracking system (see Figures 2 , ​,3). 3 ). For all participants in the current study, sound was muted and the helmets were immobilized (no head tracking), as an analog to the robot-like articulated arm goggle held eye-tracked VR goggles that will eventually be used with actual burn patients in future clinical studies. The eye-tracking interactions in the VR game were designed to be easy for the participants to make sense of how the players interact with game objects in that game/environment.

In both VR treatment conditions, each subject "glided" through the virtual world along a pre-determined path. During the interactive VR treatment condition, participants in SnowCanyon could target and shoot virtual objects in the virtual world by moving their eyes (i.e., simply looking at an object to aim snowballs at that object). The Passive VR treatment condition consisted of the identical SnowCanyon software and VR system, but with no eye-tracking and no interactivity/no snowballs. Subjects passively glided through the snowy 3D canyon in the 110 degree field of view HTC VIVE VR goggles.

Measures

After each pain stimulus, subjects received the following instructions prior to answering six separate subjective questions: "Please indicate how you felt during the most recent 10-s pain stimulus by making a mark anywhere on the line. Your response does not have to be a whole number."

After each pain stimulus, participants rated their pain using Graphic Rating Scales (GRS). Such pain rating scales have been shown to be valid through their strong associations with other measures of pain intensity, as well as through their ability to detect treatment effects ( Jensen and Karoly, 2001; Jensen, 2003; Hoffman et al., 2004c). The GRS is a 10-unit horizontal line labeled with number and word descriptors. In the current study, the tool was used to assess three reports of the pain experience ("worst pain," "pain unpleasantness," and "time spent thinking about pain") that correspond to three separable components of the pain experience; sensory pain, affective pain, and cognitive pain, respectively.

Descriptor labels were associated with each mark to help the participant rate their pain magnitude in each domain. For pain intensity, the GRS descriptors were no pain at all, mild pain, moderate pain, severe pain, and excruciating pain. For pain unpleasantness, the GRS descriptors were not unpleasant at all, mildly unpleasant, moderately unpleasant, severely unpleasant, and excruciatingly unpleasant. For time spent thinking about pain, the GRS descriptors were none of the time, some of the time, half of the time, most of the time, all of the time.

The Graphic Rating Scale has previously been used to assess pain intensity in children eight and older and has been documented to be the preferred report method for young children ( Tesler et al., 1991). The GRS is more sensitive than simple descriptive pain scales and participants can easily answer these pain ratings despite having no previous experience. Visual Analog Scales have been validated for use in children aged 7 and higher ( Bringuier et al., 2009).

A single rating "to what extent did you feel like you 'went into' the virtual world," adapted from Slater et al. (1994) was also used in the present study to assess user presence in the virtual world. Descriptor labels were I did not feel like I went inside at all, mild sense of going inside, moderate sense of going inside, strong sense of going inside, I went completely inside the computer generated world. Hendrix and Barfield (1995) showed the reliability of a similar VR presence rating. The measure's ability to detect treatment effects ( Hoffman et al., 2003a, 2004c) is preliminary evidence of our VR presence measure's validity. Participants also rated how real the objects seemed in virtual reality, descriptors were completely fake, somewhat real, moderately real, very real, indistinguishable from a real object. Participants rated nausea as a result of VR, using a graphic rating scale with descriptors no nausea at all, mild nausea, moderate nausea, severe nausea, vomit. As a surrogate measure of positive affect, participants rated how much fun they had during the painful stimulus ( Hoffman et al., 2004a). The verbal descriptors associated with the fun rating were no fun at all (0), mildly fun (1-4), moderately fun (5-6), pretty fun (7-9), and extremely fun (10). Previous studies indicate that these secondary measures are sensitive to manipulations of the immersiveness of the VR system ( Hoffman et al., 2004a, c; Wender et al., 2009).

The specific questions used in the current study were designed to assess the cognitive component of pain (amount of time spent thinking about pain), the affective component of pain (pain unpleasantness), and the sensory component of pain (worst pain). Nausea/Dizziness was assessed in an effort to identify the incidence of this component of simulator sickness sometimes associated with VR use.

Participants individually identified and pre-approved a baseline thermal pain stimulus temperature they found "painful but tolerable for 10 s, that they were willing to tolerate for two more 10 s thermal pain stimuli at that same temperature." The mean thermal stimulation temperature was 47.18°C ( SD = 0.93).

Subjective pain ratings were obtained from each healthy volunteer participant after brief thermal pain stimuli at three time points, with an interstimulus interval of approximately 4 min, using the same temperature each time: (a) baseline, (b) Test 1, and (c) Test 2.

Results

As mentioned earlier, treatment order was randomized, using random number sequences from random.org. Twenty-four participants received passive VR first and interactive eye tracked VR second (treatment order 1) and the other 24 participants received interactive eye tracked VR first and passive VR second (treatment order 2).

A two way Mixed ANOVA was conducted to test for undesired treatment order effects. The repeated measures ANOVA factor was (passive VR vs. interactive eye tracked VR), and the between groups factor was treatment order 1 vs. treatment order 2. Mixed ANOVAs showed there was no significant interaction between treatment order and worst pain ratings (i.e., no significant treatment order effects for Worst pain), F(1,46) = 1.81, p = 0.19 ns, MS = 2.04, = 0.04. There was no significant interaction between treatment order and pain unpleasantness, F(1,46) < 1, p = 0.69 ns, MS = 0.26, = 0.004. There was no significant interaction between treatment order and participants ratings of Time spent thinking about pain during the thermal stimulus, F(1,46) = 1.00, p = 0.32 ns, MS = 0.51, = 0.02. And, there was no significant interaction between treatment order and participants ratings of Fun during the thermal stimulus, F(1,46) = 1.45, p = 0.23 ns, MS = 1.76, = 0.03.

Because no significant order effects were found, the results were collapsed across treatment order for all of the analyses below.

Statistical Analyses Collapsed Across Treatment Order

One way repeated measure ANOVAs were performed to test if there were significant main effects of No VR vs. passive VR vs. interactive eye-tracked VR. Paired t-test analyses were performed for the primary outcome measure (worst pain), as well as for the secondary pain measures (i.e., pain unpleasantness, and time spent thinking about pain). For these three pain ratings, alpha was conservatively set at 0.05/3 = 0.017. Any p-value less than 0.017 was considered significant (Bonferroni corrected for familywise error). Additional paired t-test analyses were performed for the other secondary graphic rating scale measures (fun, nausea, presence, real) with α = 0.05.

WORST PAIN

A one way repeated measure ANOVA indicated a significant main effect of No VR vs. passive VR vs. interactive eye-tracked VR for worst pain, F(2,94) = 61.41, p < 0.001, MS = 92.15, partial η ² = 0.57. As predicted, compared to No VR, worst pain ratings were significantly lower during passive VR. Compared to No VR, worst pain was significantly lower during interactive eye tracked VR. And compared to passive VR, worst pain was significantly lower during interactive eye tracked VR.

Pain Unpleasantness

A one way repeated measure ANOVA showed a significant main effect of No VR vs. passive VR vs. interactive eye tracked VR for pain unpleasantness, F(2,94) = 44.33, p < 0.001, MS = 68.92, η p 2 = 0.49.

Post hoc paired comparisons (paired t-tests) are shown below. As predicted, compared to No VR, pain unpleasantness ratings were significantly lower during passive VR. Compared to No VR, pain unpleasantness was significantly lower during interactive eye tracked VR. And compared to passive VR, pain unpleasantness was significantly lower during interactive eye tracked VR.

Time Spent Thinking About Pain

A one way repeated measure ANOVA (using Greenhouse-Geisser) showed a significant main effect of No VR vs. passive VR vs. interactive eye tracked VR for "time spent thinking about pain," F(2,94) = 28.83, p < 0.001, MS = 79.49, η p 2 = 0.38.

Post hoc paired comparisons (paired t-tests) are shown below. As predicted, compared to No VR, participants ratings of time spent thinking about pain during the thermal stimulus were significantly lower during passive VR. Compared to No VR, time spent thinking about pain was significantly lower during interactive eye tracked VR. But contrary to predictions, compared to passive VR, time spent thinking about pain was NOT significantly lower during interactive eye tracked VR.

TIME Spent Thinking About PAIN

Fun During the Thermal Stimulus

A one way repeated measure ANOVA showed a significant main effect of No VR vs. passive VR vs. interactive eye tracked VR for "fun," F(2,94) = 107.40, p < 0.001, MS = 234.65, η p 2 = 0.70.

Post hoc paired comparisons (paired t-tests) are shown below. As predicted, compared to No VR, participants' ratings of fun during the thermal stimulus were significantly higher during passive VR. Compared to No VR, fun was significantly higher during interactive eye tracked VR. And compared to passive VR, fun was significantly higher during interactive eye tracked VR.

FUN

NAUSEA FROM VIRTUAL REALITY

No significant difference in "nausea during VR" was found between passive VR and interactive eye tracked VR.

Presence

Compared to their illusion of presence during passive VR, participants reported having a significantly stronger illusion of presence in virtual reality (being there), during interactive eye tracked VR.

PRESENCE IN VIRTUAL REALITY

Real

Participants rated the virtual objects as significantly more real during interactive eye tracked VR, compared to during passive VR.

HOW REAL WERE THE OBJECTS IN VIRTUAL REALITY

In order to test an important assumption of our thermal pain paradigm, pilot data collected from an additional 24 participants in the same context received No VR during baseline, No VR during Test 1 vs. No VR again during Test 2 (see Table 1 ). As predicted, participants who received No VR did not habituate to the thermal pain stimuli. In other words, the pain ratings from the thermal pain stimulations were stable over repeated pain stimulations for people who received one baseline pain and two test pain stimuli with No VR, using the same thermal pain paradigm as the main study. As predicted, as shown in Table 1 , three separate Bonferroni corrected One-Way repeated measure ANOVAs indicated no significant main effect of No VR vs. passive VR vs. interactive eye-tracked VR for worst pain, pain unpleasantness, or time spent thinking about pain.

Discussion

In the current study, we measured the brief acute pain of healthy volunteers during 10 s thermal pain stimuli to test whether increasing the immersiveness of the VR system increased how effectively VR reduces acute pain during brief thermal stimulations. As predicted, compared to passive VR, interactive eye tracked VR was significantly more effective at reducing worst pain (sensory pain), more effective at reducing pain unpleasantness (the emotional component of pain), and interactive eye tracked VR was more fun than passive VR. Furthermore, as predicted, compared to the passive VR condition, participants rated their illusion of presence significantly higher during the interactive eye tracked VR condition, and virtual objects seemed significantly more real during interactive VR, compared to passive VR.

In addition, the current study also tested an important assumption of our thermal pain paradigm. Pilot data collected from an additional 24 participants in the same context, received No VR during baseline, No VR during Test 1, and No VR again during Test 2. As predicted, the 24 participants who received No VR reported no reduction in pain. In other words, the pain ratings from the thermal pain stimulations were stable over repeated pain stimulations for people who received one baseline pain and two test pain stimuli with No VR, using the same thermal pain paradigm as the main study.

Limitations

The within-subjects study design used in the current study reduces noise variance and increases statistical power. However, one limitation of our current study is that researchers and subjects were not blinded to the treatment conditions ( Campbell and Stanley, 1963; Schulz and Grimes, 2002). In the current study, VR was "visual only" with no sound effects. Having sounds muted may have exaggerated the benefit from the eye movement interactivity. One of the advantages of VR is the multimedia exposure. Sounds of rivers running and birds singing enhance the illusion of presence and heighten the participant's sensitivity to the 3D environment. On the other hand, the lack of sound effects in the current study may have underestimated the benefits of eye movement interactivity, because there would be more sound effects in the interactive VR condition, which could make interactive VR more distracting and make the advantage of interactive VR over passive VR even more pronounced. Another limitation is that this study did not investigate/measure participants' attention level (e.g., Heathcote et al., 2017). In the current study, eye tracking technology was simply used as a naturalistic human computer interface. Future, more advanced versions of our new VR analgesia system may use eye blinks and duration of fixation to help define interactions, and further increase interactivity. In the current study, "hands free" eye tracked interactive VR was compared to passive non-interactive VR. Whether eye tracking increases analgesia compared to other "hands free" interactive VR systems (e.g., voice controlled, etc.) remains a possible topic for future research. In the current study, each individual selected a temperature they found "painful but tolerable for 10 s." Clinical research is needed to determine whether the current results generalize to clinical pain settings (e.g., for 20 min wound cleaning procedures of severe burn patients that often involve severe to excruciating pain). But, encouragingly, our first pediatric burn patient pilot subject, using the same eye tracked VR analgesia system, reported unusually large reductions in pain during burn wound care in the intensive care unit, during eye-tracked VR vs. No VR.

Despite these limitations, the current study is the first PubMed indexed VR analgesia study to involve eye tracking technology embedded into the VR goggles. Although there is a large scientific literature on traditional eye tracking spanning more than 40 years of research ( Kredel et al., 2017), there are very few studies combining eye tracking and immersive virtual reality, a very recent innovation/combination.

Why Does VR Reduce Pain? Possible Mechanisms of VR Analgesia

Although there is growing evidence that VR can be effective for reducing acute pain during painful medical procedures ( Hoffman et al., 2019), the non-pharmacologic mechanism of how VR reduces pain is not fully understood and is an important research topic. According to Ballantyne (2018, p. s25) "The conscious perception of pain depends on the conversion of nociception to perception...". The authors of the current study speculate that VR interferes with the conversion of nociception to conscious pain perception by inserting a powerful perceptual illusion into the painful experience. Instead of directing most of their attention toward converting nociceptive signals into pain perception during No VR, we speculate that during virtual reality, the patient's brain is pre-occupied with converting neural signals from the visual, auditory and other sensory systems into a multisensory perceptual illusion of "presence" in virtual reality.

In the current study, we predicted that adding hands free interactive eye tracking would make VR that much more attention grabbing, and thus more effective at reducing pain, compared to passive VR. As predicted, participants in the current study also reported a significantly stronger illusion of presence, and VR was significantly more fun during the eye tracked VR. Although the current study did not directly measure attention, the pattern of results of the current study are consistent with an attentional mechanism of how VR reduces pain (see also Hoffman, 1998, 2004; Gold et al., 2006, 2007; Dahlquist et al., 2007; Birnie et al., 2017; Gold and Mahrer, 2017; Zeroth et al., 2019).

Future Directions

Whether the current results generalize to clinical patient populations is an important topic for future research (e.g., whether eye tracking increases VR analgesia effectiveness for pediatric burn patients during burn wound care). In the current laboratory thermal pain study with healthy volunteers, eye movements were used to tell the computer what virtual objects the participant was looking at in virtual reality. In future studies on VR analgesia (e.g., virtual reality pain distraction), eye tracking technology can also be used to collect data about the patient's current mental state. For example, pupil size, and patterns of eye movements may correlate with how much pain patients are consciously experiencing. When a burn patient's pain becomes so extreme that the patient's attention shifts away from VR and onto their pain, we predict large reductions in successful eye fixations on target objects in SnowCanyon.

Immersive Virtual Reality with eye tracking has wide potential clinical uses beyond pediatric burn patients. For example, VR has recently been used with spinal injury patients ( Flores et al., 2018). Most paralyzed patients are able to move their eyes, and can thus use eye movements to interact with objects in the virtual world. In the future, eye-tracked virtual reality and also augmented reality glasses may allow people to quantify and improve the efficiency of information processing/learning, etc. And there is also growing interest in using eye tracking to help improve social skills (e.g., helping autistic patients learn to make more natural patterns of eye contact with other humans). Additional research and development is recommended.

Data Availability Statement

The datasets generated for this study are available on request to the corresponding author.

Ethics Statement

All subjects gave written informed consent in accordance with the Declaration of Helsinki. Both written and verbal informed consent were obtained using a protocol approved by the Effat University's Human Subjects Review Committee.

Author Contributions

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

Conflict of Interest

After the current study was completed, HH joined the Scientific Advisory Board of BehaVR.com, but no products or funding from this source were involved in the current study. All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

This study was completed in partial fulfillment of the requirements for the degree of Ph.D. in Computer Science by NA-G. We would like to thank Annechien Helsdingen, Ph.D., research assistants Ahad Alhudali, Nada Aljohani, Maya Akbar, Maryam Daffa and the students at Effat University who volunteered to participate in this study.

Funding

This research was supported by the King Abdulaziz City for Science and Technology (KACST) grant no. 1425-37- . This research was also supported by the Effat University Research and Consultancy Institute, in Jeddah, Saudi Arabia. HH's salary (via the University of Washington in the United States) was covered by generous support of the Mayday Fund, by NIH grant R01GM042725 to David R. Patterson, and by Shriners Hospital for Children grant (award ID #71011-GAL, PI WM).

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Articles from Frontiers in Human Neuroscience are provided here courtesy of Frontiers Media SA

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Virtual Reality Analgesia With Interactive Eye Tracking During Brief Thermal Pain Stimuli: A Randomized Controlled Trial (Crossover Design)

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Najood A. Al-Ghamdi, 1 Walter J. Meyer, III, 2, 3 Barbara Atzori, 4 Wadee Alhalabi, 5, 6, 7 Clayton C. Seibel, 8 David Ullman, 8 and Hunter G. Hoffman 8, 9, * In light of growing concerns about opioid analgesics, developing new non-pharmacologic pain control techniques has become a high priority.

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Interacting with virtual objects via embodied avatar hands reduces pain intensity and diverts attention

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Interacting with virtual objects via embodied avatar hands reduces pain intensity and diverts attention

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140079/

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Sci Rep. 2021; 11: 10672.

Abstract

The current study introduces a new paradigm for exploring cognitive factors in pain. Interacting with virtual objects via embodied avatar hands increased the illusion of "being there" in the virtual world, increased VR analgesia for acute pain, and reduced accuracy on an attention demanding task. Twenty-four healthy volunteer college students participated in this within-subject randomized crossover design study. During Phase 1, each participant received brief thermal pain stimuli during interactive embodied avatar VR vs. passive VR (no avatar and no interactivity), VR treatment order randomized. After each pain stimulus, participants provided subjective 0-10 ratings of pain. Compared to the passive VR condition, during the interactive avatar VR, participants reported significant reductions in (1) worst pain, (2) pain unpleasantness, (3) time thinking about pain and (4). they had significantly more fun during the pain stimulus ( p  = .000 for each). During Phase 2, participants performed a divided attention task in each of the two VR conditions. Participants made significantly more errors on the divided attention task during the interactive avatar VR condition, compared to passive VR, implicating an attention mechanism for how virtual reality reduces pain and helping understand how VR influences pain perception.

Trial registration: NCT04245475. Date of registration: 29/01/2020.

Subject terms: Psychology, Human behaviour

Introduction

The opioid crisis makes development of non-opioid pain control techniques a national priority1. Pain levels during medical procedures are frequently excessive. Opioid analgesics help reduce pain, and become more effective at higher doses, but opioid side effects limit dose levels7. Furthermore, unhelpful psychological influences can exacerbate/increase pain intensity during wound care, and excessive acute pain can lead to chronic pain13. Fortunately, adjunctive psychological treatments can help reduce pain, with few or no additional side effects. For example, immersive virtual reality, first reported by our team in the 1990s, is emerging as an unusually powerful adjunctive non-pharmacologic analgesic. fMRI brain scans show that in addition to reducing participants' subjective experience of pain, VR also reduces pain-related brain activity. A follow up fMRI study showed that VR reduces pain as much as a moderate dose of hydromorphone28. However, the mechanism of how VR reduces pain and why some VR systems are more effective than others, is not well understood and is the focus of the current study.

Considering VR Analgesia to be a divided attention task may help understand how VR reduces pain and why some VR systems reduce pain more effectively than other VR systems. During VR analgesia, instead of devoting all of their attention to pain, during VR, some of the patient's attention is used to process the information coming into their brain from the VR system, and simultaneously, some of their attention is used to process information coming into their brain from the pain receptors (e.g., in their skin). In other words, during VR, some of the brains attentional resources are allocated to VR, and some attentional resources are allocated to pain. The more attention grabbing the VR system, the less remaining attention the patient's brains have available to process incoming nociceptive signals, and the more effective the VR analgesia treatment (see Fig. 1 ).

In the current context, embodiment (e.g., "in a body") involves giving participants a sense of ownership over a computer generated representation of the participant, aka, an avatar29, for example "these cyberhands I see in VR, are my hands." In the current study, I predicted that interacting with virtual objects via embodied avatar hands would increase the subject's illusion of "being there" in the virtual world, would make VR more attention grabbing, would increase VR analgesia, and would reduce accuracy on an attention demanding task, implicating an attentional mechanism for how VR reduces pain.

Methods

Participants and recruitment

Twenty-four college students from the University of Washington Department of Psychology (18-24 years old, mean = 18.93 years old, SD = 1.36) were included in the main study, and an additional different 12 students participated in a side project to test the assumptions of our pain paradigm (age range 18-24). Participants in the side study received passive VR for both test phase thermal pain stimuli (instead of one passive VR and one interactive cyberhands VR condition used in the main study). All data was collected between late January and early March 2020. All participants included in each analysis were in their originally assigned treatment order groups.
Inclusion criteria:

Currently enrolled in a course at the University of Washington Psychology Dept., participating in the UW Psychology subject pool

Able to read, write and comprehend English

Able to complete study measures

Willing to follow our UW approved instructions

Exclusion criteria:

Not be able to read, write and comprehend English

Younger than 18 years of age

Not capable of completing measures

Extreme susceptibility to motion sickness

Unusual sensitivity or lack of sensitivity to pain

Diabetes.

This research was conducted in accordance with the Declaration of the World Medical Association. All participants gave written informed consent in accordance with the Declaration of Helsinki. Both written and verbal informed consent were obtained using a protocol approved by the University of Washington Human Subjects Review Committee. Informed consent was obtained for publication of any identifying information/images in an online open-access publication.

ClinicalTrials.gov Identifier: NCT04245475, date of registration 29/01/2020.

Experimental design: Within-subjects design

Phase 1: thermal pain stimulation

In addition to a baseline "no VR" thermal pain stimulus and pain rating, each of the 24 participants in the main study rated their pain during "passive VR with no cyber hands and no interactivity" during one thermal pain stimulus, and after a brief inter stimulus interval wash out period, rated their pain again during "yes interactive cyberhands avatar VR" during a second thermal stimulus. To help balance the number of participants in each treatment order, VR treatment order was block randomized using random number sequences from www.random.org. The random numbers were written on 2" paper squares, and each paper square was put into its own sealed sequentially numbered opaque envelope and was opened by the researcher as the subject was reading the consent form. To reduce bias, the researcher only learned the treatment order of an individual participant during the consent process. Participants knew they would receive two VR treatments but they only learned the details of each VR treatment (passive vs. interactive cyberhands) during the brief instructions immediately preceding each VR treatment. Using an AB/BA within subject design, with treatment order randomized, some participants received "interactive cyberhands VR" first and "passive VR with no cyberhands" second, and others received "passive VR with no cyberhands" first and "interactive cyberhands VR" second, (see participant enrollment flowchart in Fig. 2 ). "The particular strength of the simple AB/BA crossover design is that both interventions are evaluated using the same participant, which allows comparison at the individual rather than the group level" (Dwan et al. 2019, page 2)30. The within-subject design reduces nuisance variance. The VR analgesia + odd numbers protocol described herein was developed to measure for the first time how effectively a given virtual reality system reduces acute pain, and the relation between the amount attention allocated to VR, and VR analgesia effectiveness of that VR system. The current experiment involves the identification of a painful but tolerable temperature (baseline pain, no VR). After the baseline pain temperature is identified, Phase 1 begins. Phase 1 measures pain during VR. Participants experience a High Tech VR treatment during one brief pain stimulus, and they experience a Low Tech VR condition during another brief stimulus (VR treatment order randomized). Phase 2 (attention during VR) measures performance on a brief cognitive test designed to quantify how much attention is paid to the test during No VR, during High Tech VR and during Low Tech VR, by measuring the participants accuracy on the attention demanding "odd number" task during No VR, during Low Tech VR, and during High Tech VR (See Fig. 3 ).

Phase 1: quantitative sensory testing

Following the paradigm used by our team in several previous studies27,28, a commercially available Medoc Quantitative Sensory Testing thermal (heat) pain stimulator (Ramp and Hold program) was used to deliver brief 10 s heat stimuli to their right foot, at "painful but tolerable" temperatures individually pre-selected by each participant. During Phase 1, each student was allowed to choose the temperature they wanted to use during the test phase. The mean stimulus temperature selected by participants was 45.2 °C (SD = 1.40, range = 44-48.0 °C).

Participants received the following instructions. "During Phase 1, you will receive several 10 s pain stimuli. Starting at a relatively low temperature, we will slowly work our way up, one 10 s stimulus at a time, to a temperature you find painful but tolerable. You get to select which temperature to use and once you select the temperature you want to use during the test phase, you will receive only two additional 10 s stimuli at one of the temperatures you pre-approved. Phase 1 typically lasts around 10-15 min. We are not trying to see the highest pain you can tolerate, we are just wanting you to find a temperature that you find 'painful but tolerable for 10 s', that you are willing to experience for two additional 10 s stimuli, later in the study."

The instructions to participants for GRS ratings were as follows: "Please indicate how you felt during the most recent 10-s pain stimulus by making a mark anywhere on the line. Your response does not have to be a whole number." The above two sentences of instructions were presented to the subject on a conventional laptop computer screen, using a computer animated text-to-speech character software program https://ttsdemo.com/. The researcher previously typed the above two sentences of instructions into the text to speech website, and when the researcher clicked start, the animated character on the laptop screen said the brief instructions to the participant. The animated text to speech character was used to make the animated "research assistant" blind to treatment condition for at least part of the study, to help reduce bias.

After each brief thermal stimulus, participants indicated how painful they found the stimulus using Graphic Rating Scales (GRS), validated by the measures' strong associations with other measures of pain intensity, as well as through the measure's ability to detect treatment effects31-33. GRS ratings were used to measure "worst pain", "pain unpleasantness", and "time spent thinking about pain" that correspond to three separable components of the pain experience; sensory pain, affective pain, and cognitive pain, respectively.

The question regarding "to what extent did you feel like you 'went into' the virtual world," was adapted from Slater et al.34-36 Similar presence measures have been shown to be reliable and able to detect treatment effects37-41.

Equipment

The VR laptop computer MSI GeForce GTX 1080 8 GB, Intel Core i7 7th (2.80 GHz), 16 GB RAM, Windows 10 operating system was connected to a VRGineering.com XTAL VR helmet, 5120 × 1440 (2560 × 1440 per eye), with extra wide 170-180 degrees field of view, using Two Quad HD high-density OLED displays.

A VR demo Architecture World (vrgineering.com) that came with the helmet, included optical hand tracking of participants' real hands to simultaneously control their cyberhands in VR. The XTAL VR helmet came with LEAP Motion camera based optical hand tracking https://www.leapmotion.com/. The VR system was designed to give participants the illusion of "being there" in a 3D computer generated virtual house named Architecture World (VRgineering.com).

In both VR treatment conditions, each subject could see a living room in virtual reality, with a green living room chair, and two books sitting on a coffee table next to the green chair. Architecture World had no audio or sound effects in the current study.

Phase 1: measuring pain during passive VR vs. during interactive cyberhands avatar VR

For the passive VR condition, participants received the following instructions. " For this next part of the study, please put on the VR helmet, you will see a living room, and will look at a green chair, and a coffee table with books on it. While you are in VR doing this, you will receive another 10 s pain stimulus at one of the temperatures you have approved. In other words, we won't go any higher than that last stimulus you approved ". After receiving a brief thermal stimulus while in virtual reality, participants took off the VR helmet and answered the pain ratings, using the pen and paper GRS pain and presence ratings. The pain ratings and subsequent instructions phase lasted approximately 5 min, and served as the "wash out" period between VR treatments, to help minimize carryover effects.

Participants received the following instructions for the Phase 1 interactive embodied cyberhand avatar VR analgesia condition. " For this next part of the study, please put on the VR helmet, you will see a living room, and will look at a green chair, and a coffee table with books on it. Please reach out with your hand and grab one of the virtual books, drop it on the floor, grab the second virtual book, drop it on the floor and then wiggle your fingers the rest of the time. While you are in VR doing this, you will receive another 10 s pain stimulus at one of the temperatures you have approved. In other words, we won't go any higher than that last stimulus you approved. "

While in virtual reality, during the interactive embodied cyberhands avatar condition, participants could interact with objects in virtual reality using their hand movements in the real world (see Fig. 4 ). For example, they could wiggle the fingers of their cyberhand in VR by wiggling their real fingers whose detailed motion was detected by a miniature head mounted video camera attached to the XTAL VR helmet (the video camera facing outward towards the real world). With the camera based LEAP Motion system, patients did not have to hold any controllers or hardware in their hands, and did not have to wear cybergloves. The patient wearing virtual reality goggles could see their virtual hands in the virtual living room, and could use their cyberhands to interact with virtual objects in the computer generated world (pick up virtual books and drop the books onto the virtual living room floor, see Fig. 4 ). All participants were able to perform all tasks. Afterwards, they took off the VR helmet and answered the pain ratings, using the pen and paper GRS pain and presence ratings.

Phase 2: measuring the amount of attention used by passive VR with no avatar vs. interactive avatar cyberhands VR

After Phase 1, the thermal pain stimulator was removed from the participants foot, and participants were told that Phase 1 was now over, and they received the following instructions. "You have just completed Phase 1 and you can now remove the thermal pain stimulator from your foot. Please take off the thermal stimulator and put your shoe back on now. There are no more pain stimuli, but we will now begin Phase 2 of the study. In Phase 2, no pain stimuli will be administered. Instead you will go into virtual reality again and while you are in the virtual world, you will monitor a string of numbers from 1 to 10, and will say 'now' any time you hear three odd numbers in a row, (the odd numbers are 1, 3, 5, 7 or 9). For example, if you hear "1, 9, 3", you would say "now". The researcher will keep track of your answers and will be measuring your accuracy on the odd number task. You will receive a total of three divided attention tasks which each last 2 min per task. The first two minute session is with No VR. Are you ready to begin the odd number task? Just say "now" any time you hear 3 odd numbers in a row.

The researcher then played the pre-recorded auditory string of numbers (see below) via a digital audio file on a laptop with high quality Dolby Sound laptop speakers. The traditional odd number divided attention task42-45 was adapted for use in the current VR study, using our own new number set (shown below) customized for the present study (with 10 odd number triads during a 2 min session).

The string of numbers (i.e., the odd number task) lasted 2 min. The same identical two minute audio file was played a total of three times. The first time, it was played with No VR (baseline). The second time the odd number task was played during VR (e.g., passive VR) and the third time, it was played in VR again (e.g., interactive embodied avatar cyberhands VR). The VR treatment order used for the Phase 2 divided attention task was the opposite order as the VR treatment order used in Phase 1 (thermal pain stimuli), and VR treatment order was thus also randomized.

Phase 2

To summarize, the Odd Number Task is a divided attention task that involves monitoring auditory numbers during No VR (for 2 min) vs. passive VR with no cyberhands (for 2 min) vs. during interactive cyberhands avatar VR (for two minutes). During the "dual task", participants must perform the two tasks at the same time, being in VR was one task, and monitoring the odd number task was a competing task. In each condition, participants listened to an auditory string of numbers from 1 to 10, and said "now" every time they heard three odd numbers in a row. They were told that the researcher would be monitoring their accuracy on the odd number task. During the odd number task, the researcher had a printout of the number sequence, and the researcher made a mark to indicate every time the participant said "now" in each of the following conditions.

No VR + odd number task

Participants did not wear a VR helmet during the No VR condition. They monitored the odd number task with No VR.

Passive VR condition + odd number task

During the passive VR condition, participants went into a virtual living room, and were instructed to look at the green chair, coffee table and the books on the coffee table in VR. They could not see any cyberhands or avatar in virtual reality in this treatment condition (passive, no cyberhands). While they were in passive VR during the Phase 2 divided attention task, as they were in VR looking at the living room chair scene, they also listened to an auditory string of numbers, and said "now" any time they heard three odd numbers in a row.

Interactive embodied cyberhands avatar condition + odd number task

While they were in VR during the Phase 2 divided attention task, they looked at the living room chair scene, they used their cyberhands to pick up books in VR, and wiggled their cyberfingers at the same time they listened to an auditory string of numbers, and said "now" any time they heard three odd numbers in a row.

Power analysis

A power analysis to determine the number of participants needed to test our primary hypothesis was computed apriori, using the statistical program GPower 3.10. The following assumptions were used in the power analyses, all determined from pilot data and Wender et al. 200941, an effect size (d) of .78, power of .95, and an alpha of .05. Under these conditions, we would require 24 participants in the main study to be able to detect a significant treatment effect, and to show that interactive cyberhands treatment was more effective than passive VR for reducing acute worst pain during the brief thermal pain stimuli.

Results

Pre-analysis for carry-over effects.

When using a within-subjects design, carry over effects sometimes occur when the effect of the first treatment condition persists, and influences the responses of the second treatment, so that the observed difference between the treatment conditions depends on the treatment order30.

The following pre-analysis was conducted to see if there were carry over effects (i.e., to see if the difference between passive VR and interactive avatar VR was stronger depending on which treatment order (passive 1st or passive 2nd). As shown below, non-parametric comparisons were used to test if there were undesired carryover treatment order effects. The difference between Passive VR vs. interactive cyberhands was the dependent variable, and treatment order was the between groups factor (people who received passive VR 1st were considered one group, and those who received passive VR second were considered a second group). No significant interaction was found between treatment order and worst pain ratings (i.e., no significant treatment order effects for Worst pain). No significant interaction was found between treatment order and pain unpleasantness. No significant interaction was found between treatment order and participants' ratings of Time spent thinking about pain during the thermal stimulus. And finally, no significant interaction was found between treatment order and participants ratings of Fun during the thermal stimulus.

Test statisticsa

worstdif

thinkdif

unpldif

fundif

Exact Sig. [2*(1-tailed Sig.)]

.487 b

.833 b

.566 b

.235 b

a Grouping variable: (Passive 1st = Group 1), (Interactive avatar 1st = Group 2)

b Not corrected for ties

Since there were no carry over effects, all of the following analyses were collapsed across treatment order (see Figs. 5 , ​,6 6 and ​and7 7 ).

Worst pain (the primary dependent variable)

A Friedman test showed a significant main effect of No VR vs. passive VR vs. interactive cyberhands VR for the primary dependent measure, Worst Pain, χ2 (2) = 31.74, p = .000 (see Fig. 5 ). Post-hoc paired comparisons (Wilcoxin signed rank tests) are shown below. (1) Comparing No VR vs. passive VR, worst pain ratings were NOT significantly lower during passive VR, but showed the predicted pattern. (2) Comparing No VR vs interactive cyberhands VR, worst pain was significantly lower during interactive cyberhands VR. And (3) Most importantly, comparing passive VR vs. interactive cyberhands VR, worst pain was significantly lower during interactive cyberhands VR.

Primary dependent variable

Worst pain, mean ratings on a zero to 10 graphic rating scale (SD in parentheses)

No

VR (baseline)

Passive VR

Interactive cyberhands avatar VR

Wilcoxin signed rank tests

Pain unpleasantness (a secondary pain measure)

A Friedman test showed a significant main effect of No VR vs. passive VR vs. interactive cyberhands VR for pain unpleasantness, χ2 (2) = 34.87, p  = .000.

Post hoc paired comparisons (Wilcoxin signed rank tests) for the variable "pain unpleasantness" are shown below. (1) Comparing No VR vs. passive VR, pain unpleasantness was significantly lower during passive VR. (2) Comparing No VR vs. interactive cyberhands VR, pain unpleasantness was significantly lower during interactive cyberhands VR. And (3) Most importantly, as predicted, comparing passive VR vs. interactive cyberhands VR, pain unpleasantness was significantly lower during interactive cyberhands VR.

Unpleasantness, mean ratings on a zero to 10 graphic rating scale (SD in parentheses).

No

VR (baseline)

Passive VR

Interactive cyberhands avatar VR

Wilcoxin signed rank tests

Time spent thinking about pain (a secondary pain measure)

A Friedman Test showed a significant main effect of No VR vs. passive VR vs. interactive cyberhands VR for time spent thinking about pain, χ2 (2) = 31.17, p  = .000.

Post hoc paired comparisons (Wilcoxin signed rank tests) for the variable "time spent thinking about pain" are shown below. (1) Although in the predicted direction, No VR vs. passive VR was nonsignificant. (2) Comparing No VR vs. interactive cyberhands VR, time spent thinking about pain was significantly lower during interactive cyberhands VR. And (3) Most importantly, as predicted, comparing passive VR vs. interactive cyberhands VR, time spent thinking about pain was significantly lower during interactive cyberhands VR.

Time spent thinking about pain

No

VR (baseline)

Passive VR

Interactive cyberhands avatar VR

Wilcoxin signed rank tests

Fun

A Friedman Test showed a significant main effect of No VR vs. passive VR vs. interactive cyberhands VR for Fun during the thermal stimulus, χ2 (2) = 30.61, p  = .000.

Post hoc paired comparisons (Wilcoxin signed rank tests) for the variable "Fun" are shown below. (1) comparing No VR vs. passive VR, participants reported having significantly more fun during passive VR. (2) Compared to No VR, interactive cyberhands VR was significantly more fun. And (3) Most importantly, compared to passive VR, interactive cyberhands VR was significantly more fun.

Fun during the thermal stimulus, mean ratings on a zero to 10 graphics rating scale (SD in parentheses).

No

VR (baseline)

Passive VR

Interactive cyberhands avatar VR

Wilcoxin signed rank tests

Presence

Compared to their illusion of presence during passive VR, participants reported having a significantly stronger illusion of presence in virtual reality (being there), during interactive cyberhands VR (where higher presence ratings are better, on a zero to ten rating scale).

Presence in virtual reality

Passive VR

Interactive cyberhands avatar VR

Wilcoxin Signed Rank Test

4.42 (2.33)

5.76 (2.16)

Z = − 3.32, p  = .001

How real were the objects in virtual reality

Passive VR

Interactive cyberhands avatar VR

Wilcoxin Signed Rank Test

4.87 (1.91)

5.48(1.87)

Z = − 2.65, p  = .008

Nausea in VR

Passive VR

Interactive cyberhands avatar VR

Wilcoxin Signed Rank Test

0.31 (70)

0.39 (.89)

Z = − .85, p  = .40 NS

Phase 2: performance on the traditional divided attention task

In order to measure participants' accuracy on the odd number divided attention task, participants listened to a string of auditory numbers and participants said "now" any time they heard three odd numbers in a row.

A Friedman Test showed a significant main effect of No VR vs. passive VR vs. interactive cyberhands VR for accuracy (mean number of hits out of 10 possible hits) on the odd number task, χ2 (2) = 17.47, p  = .000.

Accuracy (mean number of hits on the odd number task out of 10 possible hits during each 2 min odd number session (e.g., 9/10 hits = 9.00 = 90% accurate, with SD in parentheses).

No VR

Passive VR

Interactive Cyberhand VR

Wilcoxin Signed Rank Test

9.60 (.68)

9.00 (1.26)

Z = 2.08, p  = .038

9.62 (.68)

7.62 (2.13)

Z = 3.39, p  = .001

9.05 (1.24)

7.67 (2.13)

Z = 2.69, p  = .007

Exploratory side study

To test some important assumptions of our thermal pain paradigm, pilot data collected from 12 new participants from the same subject pool, who were not involved in the main study, received No VR during baseline, passive VR during thermal Test 1 vs. passive VR again during thermal Test 2. As predicted, participants' pain ratings from the thermal pain stimulations were stable over repeated test pain stimulations for people who received one baseline pain and two test pain stimuli with passive VR, using the same thermal pain paradigm as the main study.

As shown below, several non-parametric Friedman tests indicated no significant difference between No VR, passive VR on Test 1 vs. passive VR again on Test 2 for worst pain, pain unpleasantness, time spent thinking about pain, or fun during the pain stimulus. In other words, fortunately there was no evidence of habituation to the thermal pain stimulus. For this side pilot study, the same thermal stimulus elicited similar ratings for each of the three pain stimuli (Fig. 8 ).

Worst pain during No VR = 3.96 (1.25)

Worst pain during passive VR 1st time = 3.58 (1.50)

Worst pain during passive VR 2nd time = 3.72 (1.48)

Pain Unpleasantness during No VR = 3.97 (1.13)

Pain Unpleasantness during passive VR 1st time = 3.67 (1.44)

Pain Unpleasantness during passive VR 2nd time = 3.63 (1.55)

Time spent thinking about pain during No VR = 4.75 (2.26)

Time spent thinking about pain during passive VR 1st time = 3.79 (2.46)

Time spent thinking about pain during passive VR 2nd time = 3.88 (1.84)

Fun during pain stimulus during No VR = 3.83 (2.52)

Fun during pain stimulus during passive VR 1st time = 4.38 (2.69)

Fun during pain stimulus during passive VR 2nd time = 3.96 (2.60)

Discussion

In the current study, as predicted, interacting with virtual objects via embodied avatar hands (i.e., avatar VR) significantly increased the participant's illusion of "being there" in the virtual world, increased VR analgesia, and increased fun during the pain stimulus. The current study also measured for the first time, how much attention was diverted by avatar VR. Consistent with the notion that interactive embodied immersive VR is unusually attention grabbing, during Phase 2, participants made significantly more errors on the divided attention task during the interactive avatar VR condition, compared to passive VR. These results implicate an attentional mechanism for how VR reduces pain, and help understand how VR influences pain perception.

Although immersive virtual reality can often help reduce the acute pain of patients during painful medical procedures, some medical procedures are so painful that extra strength VR analgesia may be needed46. The current study measured whether a stronger (more immersive) dose of virtual reality could increase analgesia. Our results indicate that the immersiveness of a VR system can be increased substantially, (e.g., via avatars) with little or no increase in VR side effects, unlike opioids, which show a dose-response increase in side effects (e.g., increased nausea and constipation) with higher doses, and opioid side effects linger for hours after the medical procedure. Immersive interactive cyberhand avatar embodiment with extra wide field of view VR helmet (180 degrees field of view, high resolution) appears to have considerable potential as a short acting extra strength VR analgesia system. A number of studies have now shown that increasing the immersiveness of the VR system increases VR analgesia for acute. In addition, the relationship between having a body/avatar in VR and presence has been shown previously and the current results contribute to those findings.

However, according to Trost et al. 202026, there is currently a gap in the scientific literature on the use of immersive VR avatars to treat acute pain. To date, nearly all studies involving virtual embodiment have targeted treatments designed for chronic pain patients, (e.g., phantom limb pain). The current study is one of the first VR studies designed to treat acute pain that includes an avatar, and is the first acute pain VR analgesia study to manipulate embodiment, and to measure whether interactive embodiment with cyberhands avatars increases analgesia (and reduces accuracy on the odd number task, an objective measure of attention), compared to passive VR with no avatar, a promising direction for future research.

The current study has a number of limitations that should be taken into consideration when interpreting the results. The within-subjects design is statistically powerful and allows each participant to compare the different treatments, but has the drawback that participants remain aware of the different treatment conditions, and this awareness has the potential to influence the results56. The current study should thus be replicated using a between groups design, ideally with participants blinded to VR treatment group conditions57, and using a larger sample size.

Even though the sense of presence in the VR environment was assessed among the participants, it would be interesting (in future investigations) to also measure how strong the sense of embodiment was in terms of body ownership, agency, and self-location to investigate possible relationships with the distraction from pain effect. Another limitation is that the current study is an analog laboratory pain study, with only brief thermal pain stimuli and brief VR treatment durations. Whether the current results generalize to clinical settings (e.g., severely burned children during 20 min burn wound debridement sessions) is an important research topic for future clinical studies with patients during painful medical procedures, e.g.,.

Despite these limitations, the results of this study could also have other important clinical implications. According to Keefe et al.1, the epidemic of opioid related overdose deaths has greatly increased the urgency to develop effective non-drug pain control techniques that can help reduce the medical community's current heavy reliance on opioid analgesics for pain control. Although to date VR analgesia has typically been used adjunctively in addition to traditional pain medications, a stronger version of VR has the potential to reduce the use of opioids and/or to help compensate for increasing tendencies to under-medicate patients, as opioids become much more strictly controlled, due to recent increases in federal regulation of opioid prescription.

Future Directions. According to Matamala-Gomez et al, p 162 "Using such virtual embodiment to manipulate body perception is starting to be extensively investigated and may have clinical implications for conditions that involve altered body image such as chronic pain." Researchers are currently developing/exploring the use of high-tech immersive virtual reality embodiment therapy (e.g., embodied avatar cyberhands) for phantom limb pain and other chronic pain diseases, to create a more compelling illusion of limb ownership and to help treat phantom limb pain more effectively. There is some evidence that for some chronic pain patients, illusions can be used to help reduce persistent pain, and perhaps normalize maladaptive pathological distortions of the patient's homunculus.

Patients wearing a VR helmet look down and see two virtual arms and two virtual hands. They are able to use their virtual body/hand to interact with objects in the virtual world. This can potentially be used for both amputees and nonamputee chronic pain patients.

Major computer companies' multibillion dollar investments into virtual reality technology are making VR goggles widely available and affordable for medical applications, and the VR technologies needed to include avatars into a virtual environment have become much simpler and inexpensive. Avatar technology and the ability to socialize in multi-participant networked VR is rapidly improving. Additional research and development of VR analgesia is recommended.

Acknowledgements

The author does not have any conflicts of interest. The author is on the Scientific Advisory Board of BehaVR.com but no products or funding from this source was involved in the conduct of the study in the current manuscript, and these are not considered a competing interest. The current study was philanthropically funded by the Mayday Fund to the University of Washington, PI = Hunter Hoffman. Special thanks to Christina M. Spellman for thought provoking discussions.

Author contributions

HH designed, conducted, analyzed and wrote.

Competing interests

The author declares no competing interests.

Footnotes

Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

22. Khadra C, et al. Effects of a projector-based hybrid virtual reality on pain in young children with burn injuries during hydrotherapy sessions: A within-subject randomized crossover trial. Burns. 2020 doi: 10.1016/j.burns.2020.04.006. [[ PubMed] [ CrossRef] Google Scholar]

42. Craik F. On the transfer of information from temporary to permanent memory. Philos. Trans. R. Soc. B. 1983;302:341-359. [ Google Scholar]

46. Firoozabadi R, et al. Case report: Virtual reality analgesia in an opioid sparing orthopedic outpatient clinic setting: A case study. Front. Virtual Real. 2020 doi: 10.3389/frvir.2020.553492. [[ PMC free article] [ PubMed] [ CrossRef] Google Scholar]

49. Martini M, Kilteni K, Maselli A, Sanchez-Vives MV. The body fades away: investigating the effects of transparency of an embodied virtual body on pain threshold and body ownership. Sci. Rep. 2015 doi: 10.1038/srep13948. [[ PMC free article] [ PubMed] [ CrossRef] Google Scholar]

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Articles from Scientific Reports are provided here courtesy of Nature Publishing Group

# data[].attributes.attachment_link.title
Interacting with virtual objects via embodied avatar hands reduces pain intensity and diverts attention

# data[].attributes.attachment_link.description
Sci Rep. 2021; 11: 10672. The current study introduces a new paradigm for exploring cognitive factors in pain. Interacting with virtual objects via embodied avatar hands increased the illusion of "being there" in the virtual world, increased VR analgesia for acute pain, and reduced accuracy on an attention demanding task.

# data[].attributes.headline
Virtual Reality and Symptoms Management of Anxiety, Depression, Fatigue, and Pain: A Systematic Review

# data[].attributes.subject
Virtual Reality and Symptoms Management of Anxiety, Depression, Fatigue, and Pain: A Systematic Review

# data[].attributes.body
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774450/

# data[].attributes.attachment_link.title
Virtual Reality and Symptoms Management of Anxiety, Depression,
Fatigue, and Pain: A Systematic Review

# data[].attributes.attachment_link.description
In recent years, virtual reality (VR) has become an interesting alternative to
traditional exposure-based therapies for many symptoms. VR involves immersion in
a computer-generated virtual environment that minimizes avoidance and
facilitates emotional ...

# data[].attributes.headline
Virtual reality distraction for acute pain in children

# data[].attributes.subject
Virtual reality distraction for acute pain in children

# data[].attributes.body
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094164/

# data[].attributes.attachment_link.readable_text
Cochrane Database Syst Rev. 2020; 2020(10): CD010686.

Abstract

Background

Virtual reality (VR) computer technology creates a simulated environment, perceived as comparable to the real world, with which users can actively interact. The effectiveness of VR distraction on acute pain intensity in children is uncertain.

Objectives

To assess the effectiveness and adverse effects of virtual reality (VR) distraction interventions for children (0 to 18 years) with acute pain in any healthcare setting.

Search methods

We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and four trial registries to October 2019. We also searched reference lists of eligible studies, handsearched relevant journals and contacted study authors.

Selection criteria

Randomised controlled trials (RCTs), including cross‐over and cluster‐RCTs, comparing VR distraction to no distraction, non‐VR distraction or other VR distraction.

Data collection and analysis

We used standard Cochrane methodological processes. Two reviewers assessed risk of bias and extracted data independently. The primary outcome was acute pain intensity (during procedure, and up to one hour post‐procedure). Secondary outcomes were adverse effects, child satisfaction with VR, pain‐related distress, parent anxiety, rescue analgesia and cost. We used GRADE and created 'Summary of findings' tables.

Main results

We included 17 RCTs (1008 participants aged four to 18 years) undergoing various procedures in healthcare settings. We did not pool data because the heterogeneity in population (i.e. diverse ages and developmental stages of children and their different perceptions and reactions to pain) and variations in procedural conditions (e.g. phlebotomy, burn wound dressings, physical therapy sessions), and consequent level of pain experienced, made statistical pooling of data impossible. We narratively describe results.

We judged most studies to be at unclear risk of selection bias, high risk of performance and detection bias, and high risk of bias for small sample sizes. Across all comparisons and outcomes, we downgraded the certainty of evidence to low or very low due to serious study limitations and serious or very serious indirectness. We also downgraded some of the evidence for very serious imprecision.
1: VR distraction versus no distraction Acute pain intensity: during procedure
Self‐report: one study (42 participants) found no beneficial effect of non‐immersive VR (very low‐certainty evidence).

Observer‐report: no data.

Behavioural measurements (observer‐report): two studies, 62 participants; low‐certainty evidence. One study (n = 42) found no beneficial effect of non‐immersive VR. One study (n = 20) found a beneficial effect favouring immersive VR.
Acute pain intensity: post‐procedure
Self‐report: 10 studies, 461 participants; very low‐certainty evidence. Four studies (n = 95) found no beneficial effect of immersive and semi‐immersive or non‐immersive VR. Five studies (n = 357) found a beneficial effect favouring immersive VR. Another study (n = 9) reported less pain in the VR group.

Observer‐report: two studies (216 participants; low‐certainty evidence) found a beneficial effect of immersive VR, as reported by primary caregiver/parents or nurses. One study (n = 80) found a beneficial effect of immersive VR, as reported by researchers.

Behavioural measurements (observer‐report): one study (42 participants) found no beneficial effect of non‐immersive VR (very low‐certainty evidence).

Adverse effects: five studies, 154 participants; very low‐certainty evidence. Three studies (n = 53) reported no adverse effects. Two studies (n = 101) reported mild adverse effects (e.g. nausea) in the VR group.
2: VR distraction versus other non‐VR distraction Acute pain intensity: during procedure
Self‐report, observer‐report and behavioural measurements (observer‐report): two studies, 106 participants:

Self‐report: one study (n = 65) found a beneficial effect favouring immersive VR and one (n = 41) found no evidence of a difference in mean pain change scores (very low‐certainty evidence).

Observer‐report: one study (n = 65) found a beneficial effect favouring immersive VR and one (n = 41) found no evidence of a difference in mean pain change scores (low‐certainty evidence).
Acute pain intensity: post‐procedure
Behavioural measurements (observer‐report): one study (n = 65) found a beneficial effect favouring immersive VR and one (n = 41) reported a difference in mean pain change scores with fewer pain behaviours in VR group (low‐certainty evidence).

Self‐report: eight studies, 575 participants; very low‐certainty evidence. Two studies (n = 146) found a beneficial effect favouring immersive VR. Two studies (n = 252) reported a between‐group difference favouring immersive VR. One study (n = 59) found no beneficial effect of immersive VR versus television and Child Life non‐VR distraction. One study (n = 18) found no beneficial effect of semi‐immersive VR. Two studies (n = 100) reported no between‐group difference.

Observer‐report: three studies, 187 participants; low‐certainty evidence. One study (n = 81) found a beneficial effect favouring immersive VR for parent, nurse and researcher reports. One study (n = 65) found a beneficial effect favouring immersive VR for caregiver reports. Another study (n = 41) reported no evidence of a difference in mean pain change scores.

Behavioural measurements (observer‐report): two studies, 106 participants; low‐certainty evidence. One study (n = 65) found a beneficial effect favouring immersive VR. Another study (n = 41) reported no evidence of a difference in mean pain change scores.
3: VR distraction versus other VR distraction
Adverse effects: six studies, 429 participants; very low‐certainty evidence. Three studies (n = 229) found no evidence of a difference between groups. Two studies (n = 141) reported no adverse effects in VR group. One study (n = 59) reported no beneficial effect in reducing estimated cyber‐sickness before and after VR immersion.

We did not identify any studies for this comparison.

Authors' conclusions

We found low‐certainty and very low‐certainty evidence of the effectiveness of VR distraction compared to no distraction or other non‐VR distraction in reducing acute pain intensity in children in any healthcare setting. This level of uncertainty makes it difficult to interpret the benefits or lack of benefits of VR distraction for acute pain in children. Most of the review primary outcomes were assessed by only two or three small studies. We found limited data for adverse effects and other secondary outcomes. Future well‐designed, large, high‐quality trials may have an important impact on our confidence in the results.

Plain language summary

What are the benefits and risks of using virtual reality in a healthcare setting to distract children from pain? Why is this question important?
Medical procedures, such as health examinations or injections, can cause children to experience pain. In these situations, it is common practice to distract children using toys or play, in order to minimise distress and fear of pain.

One form of distraction that can be used is virtual reality. Virtual reality is an artificial environment with scenes and objects that appear to be real (for example a frozen world, or a wildlife park). Virtual reality can be:

‐ Fully‐immersive: users typically wear a headset with headphones and a screen, and interact with the virtual environment as if they were really in it.

‐ Semi‐immersive: users interact with a partially virtual environment (for example, a flight simulator where the controls are real, but the windows display virtual images).

‐ Non‐immersive: the user is connected to the virtual world by a separate monitor (for example, a computer) but can still experience the real world.

To find out whether virtual reality can distract children from pain, and whether it is associated with any adverse (unwanted) effects, we reviewed the research evidence.
How did we identify and evaluate the evidence?
We searched the medical literature for randomised controlled studies (clinical studies where people are randomly put into one of two or more treatment groups), because these provide the most robust evidence about the effects of a treatment. We compared and summarized their results. Finally, we rated our confidence in the evidence, based on factors such as study methods and sizes, and the consistency of findings across studies.
What did we find?
We found 17 studies that involved a total of 1008 children aged from four to 18 years. Medical procedures included injections, taking blood, changing wound dressings, and physical exercise. Studies compared virtual reality against no distraction, or against non‐virtual distraction. No studies compared different types of virtual reality.
During a medical procedure
We cannot tell whether virtual reality reduces self‐reported pain during a medical procedure because we have too little confidence in the evidence available (three studies).

Only two studies investigated changes in pain assessed by an observer (for example, using a rating scale that ranges from 0 (no pain) to 10 (great pain)). These reported conflicting findings: in one study fully‐immersive virtual reality was beneficial compared to non‐virtual distraction, but not in the other.

Fully‐immersive virtual reality may reduce pain assessed by an observer based on children's behaviour (for example, crying, or rubbing a body part in a way that indicates pain) more effectively than non‐virtual distraction (two studies) or no distraction (one study).

Non‐immersive virtual reality was not beneficial for pain assessed by an observer based on children's behaviour compared to no distraction (one study).

A fter a medical procedure

We cannot tell whether virtual reality can reduce self‐reported pain after a medical procedure, as we have too little confidence in the evidence available (16 studies).

Five studies investigated changes in pain assessed by an observer. Virtual reality was beneficial compared to no distraction in two studies, and also when compared to non‐virtual distraction in another two studies. However, it was no better than non‐virtual distraction in one study.

Two studies investigating pain assessed by an observer based on children's behaviour reported conflicting findings: immersive virtual reality was beneficial compared to non‐virtual distraction in one study, but not in the other.

We cannot tell whether there is a difference between virtual reality and no distraction for pain assessed by an observer based on children's behaviour, as we have too little confidence in the available evidence (one study).
Adverse effects
We cannot tell if virtual reality is associated with adverse effects because we have too little confidence in the evidence available (11 studies).
What does this mean?
We have little to very little confidence in the evidence we identified. It is unclear from our review whether virtual reality distraction makes a difference to pain in children. There is a need for large, well‐designed studies in this area.
How up‐to date is this review?
The evidence in this Cochrane Review is current to October 2019.

Summary of findings

Background

Description of the condition

Healthcare examinations, treatments, procedures and interventions are typical extreme stressors that can lead to pain for children ( Clift 2007; Fox 2016; Horstman 2002; Melnyk 2000; Racine 2016; Rassin 2004; Wollin 2004). A recent definition describes pain as "a distressing experience associated with actual or potential tissue damage with sensory, emotional, cognitive, and social components" ( Williams 2016). Similar to the International Association for the Study of Pain (IASP) original definition of pain ( IASP 2011), this definition highlights that pain has both distressing sensory (i.e. pain intensity) and emotional (i.e. any negative affect secondary to pain such as distress; including anxiety, fear and/or stress) features, associated with actual or potential tissue damage. The sensory and emotional correlates of pain are 'subjective psychological states' ( Aydede 2017) and can sometimes be difficult to distinguish between ( Brown 2012; Curtis 2012; Goodenough 1999; McGrath 2008). This may be especially the case for children under eight years of age, who by virtue of their developmental abilities may be unable to differentiate pain meaningfully from other unpleasant emotions such as fear and anxiety ( Blount 2006; Goodenough 1999). These two dimensions of pain (i.e. pain intensity and pain‐related distress) are important to consider in ensuring pain management strategies reduce not only pain intensity but also the distress, anxiety and/or fear associated with medical treatment‐related pain ( Goodenough 1999).

Pain impacts on child and parent satisfaction with healthcare delivery and services. In an investigation of the views and experiences of children in Council of Europe member states, Kilkelly 2011 found that 60.1% of child participants rated 'not being in pain' as an important element of health care. Yet evidence suggests that acute pain management in children is not always optimal ( Cummings 1996; Groenewald 2012; Taylor 2008). Figures estimate that 27% of children experience moderate to severe pain in hospital, with teenagers and infants experiencing higher prevalence rates of 38% and 32% respectively ( Groenewald 2012). This can impact on children's physiological, psychological and emotional well‐being, in both the short and long term.

It is inevitable that children admitted to healthcare settings will likely be exposed to potentially painful procedures on a daily basis. For instance, Stevens 2011 reported that more than three‐quarters (78.2%) of child participants (n = 3822) in their study had undergone at least one painful procedure in a 24‐hour period preceding data collection. While each child was exposed to an average of 6.3 (range 1 to 50) procedures, only a small portion (28.3%) of children had interventions specifically linked to the painful procedure. While acknowledging that certain procedures are essential for routine medical and surgical care, these procedures/treatments can cause pain for the child. Children can feel "threatened by the monster of medical care" where they fear being hurt, forced and violated by the adults delivering that care ( Forsner 2009). Pain results in anxiety and stress, which, in turn, negatively impacts not only on a child's ability to cope with the treatment/intervention but also on their recovery ( Li 2009). Inadequate relief of pain during childhood treatments may have long‐term negative effects on future pain tolerance and pain responses ( Young 2005).

Non‐pharmacological techniques (e.g. imagery, hypnosis, story‐telling, play, music) have long been promoted as useful adjuncts to pharmacological analgesics ( Butler 2005; Klassen 2008; Landier 2010). Yet, aside from distraction and hypnosis, and more recently combined cognitive behavioural therapy and breathing, there is limited evidence to support the efficacy of many of these conventional psychological interventions (e.g. relaxation, guided imagery, music) for reducing procedure‐related pain in children ( Birnie 2018; Stinson 2008). In addition, it has been documented that children may benefit more from interactive (e.g. playing a video game) as opposed to passive (e.g. watching a video game) distraction strategies ( Wohlheiter 2013). One such recent 'active' adjunctive analgesic technique gaining momentum is virtual reality (VR) ( Hoffman 2011).

With the use of technology becoming increasingly prevalent in children's daily lives, alongside the drive towards e‐health and the empowered patient, it seems reasonable to propose that interactive technologies, if proven effective, should be considered as vital intervention vehicles for enhancing health outcomes for children. The use of VR during healthcare procedures/treatments can create a child‐friendly and developmentally sensitive environment, thereby contributing to the European campaign for a child‐friendly approach to health care ( Council of Europe 2011).

Description of the intervention

The content of some VR interventions has been developed specifically for certain types of procedures (e.g. Snow World and Ice Cream Factory, devised for burn wound dressings) ( Chan 2007; Hoffman 2004a), whereas other VR interventions (e.g. Virtual Gorilla) are selected for convenience to engage children at the time of invasive medical procedures ( Gershon 2003; Wolitzky 2005). All VR systems are categorised according to how immersive or non‐immersive they are. With non‐immersive systems, the user is connected to the virtual world (by an external monitor) but can still communicate with the real world (e.g. the healthcare environment; Nilsson 2009). With full immersion, the user's visual and auditory perception and haptics of stimuli in the outside world is blocked as they become fully enveloped in the computer‐generated virtual environment through the use of a head‐mounted display and a tracker position sensor (e.g. a helmet and headphones which exclude visual and auditory inputs from the healthcare environment; Gold 2006; Weiss 2003). It is this sense of presence and immersive attention (i.e. the ability to give users the sense they are somewhere else) that sets VR apart from other technological interventions such as watching television or video movies, or playing simulated or interactive video games ( Chan 2007; Gorini 2011; Hoffman 2004a; Nilsson 2009; Steele 2003; Weiss 2003).

How the intervention might work

VR has been used in many contexts (e.g. treating phobias and post‐traumatic stress disorders; training military and medical personnel). For the purposes of this review, the focus is on the use of VR in the reduction of acute pain intensity and pain‐related distress associated with medical treatments/interventions in any healthcare setting. The theory of how VR works in such instances is as a form of distraction; where distraction is referred to as purposefully directing attention away from undesirable sensations ( Mobily 1993). Distraction is a common coping mechanism used by school aged children and adolescents for enduring unpleasant situations ( Schneider 2000). Distraction interventions function by diverting the child's attention away from the stimulus producing the pain and refocusing the child's attention towards a more pleasant and positive stimulus (i.e. the virtual environment; McCaul 1984; Schneider 2000). VR interventions are thought to manifest analgesic effects by altering pain perception through distracting user attention away from the painful procedure, in addition to changing the way a person interprets incoming pain signals, consequently reducing the amount of pain‐related brain activity (as seen on MRI imagery) ( Morris 2009). VR exposure can target cognitive and affective pain pathways, thereby decreasing pain intensity, distress, and anxiety by altering how pain signals are processed in the central nervous system. This is achieved by a number of mechanisms including attentional distraction, conditioning of VR imagery and reduced pain.

VR distraction has been used, for example, to minimise children's anxiety associated with chemotherapy ( Ahmadi 2001; Schneider 1999), to reduce children's pain during burn wound care ( Hoffman 2000; Hoffman 2001; Hoffman 2004a), to access intravenous ports in paediatric oncology patients ( Wolitzky 2005), to alleviate pain/anxiety for invasive medical procedures such as venipuncture, lumbar puncture, and bone marrow aspirates ( Gershon 2003; Gold 2006; Nilsson 2009; Wint 2002), to help adolescents with cerebral palsy as they endure physiotherapy ( Steele 2003), and to reduce children's preoperative anxiety using handheld video games or films ( Low 2008; Patel 2006). Together with pharmacological interventions, distraction is thought to be an effective pain management strategy by cognitively redirecting attention away from pain to a more pleasant stimulus, thereby assisting children to cope with the distress of medical treatments. Long‐term benefits include advantages for later adult life, as pain experienced during medical treatments in childhood is predictive of pain during subsequent medical procedures and avoidance of medical care during young adulthood ( Blount 2006).

Why it is important to do this review

VR is a recent technological advancement with the potential to modulate children's pain when they are undergoing healthcare treatments (e.g. intravenous cannulation, lumbar puncture, wound dressings, chemotherapy, bone marrow aspirates). For instance, Gold 2006 reported that children who underwent intravenous cannulae placement without distraction reported a fourfold increase in affective pain when compared to children immersed in a VR intervention. Additionally, children who received a VR intervention were twice as satisfied with their pain management as compared to children not exposed to a VR intervention. Schneider 2000 found 82% of children indicated that their chemotherapy treatment was better with VR as compared to previous chemotherapy treatment without VR. Parents were also satisfied with the use of VR interventions and believed such interventions did reduce children's pain and enhance children's cooperation during medical treatments ( Gold 2006). In a review, Hoffman 2011 reported a 35% to 50% reduction in procedural pain in burn patients when in a distracting immersive VR.

Despite these positive evaluations and reports of pain reduction, there remains uncertainty over the effectiveness of VR interventions ( Dahlquist 2010; Garrett 2014; Kenney 2016; Malloy 2010; Morris 2009). In addition, in comparison to other simpler forms of non‐pharmacological distraction interventions (e.g. imaginary, breathing, positive thinking), there have been some common criticisms levelled at VR such as high costs, bulky equipment, the need for specialist technological skills and the potential for cyber‐sickness, all of which may threaten the widespread implementation of VR for therapeutic healthcare interventions ( Bohil 2011). It is important to conduct this systematic review to evaluate the effectiveness of VR as a pain distractor during healthcare treatments. As few psychological interventions incorporate, or evaluate the effectiveness of, modern and novel interactive technologies such as VR, this review complements other Cochrane Reviews (e.g. Birnie 2018) that evaluate the effectiveness of non‐pharmacological distraction‐based interventions for minimising pain in children when undergoing medical treatments.

Objectives

To assess the effectiveness and adverse effects of VR distraction interventions for children (0 to 18 years) with acute pain in any healthcare setting.

Methods

Criteria for considering studies for this review

Types of studies

We included randomised controlled trials (RCTs), including cross‐over and cluster‐RCTs.

Types of participants

We included children aged from birth up to and including 18 years, with acute pain in any healthcare setting.

Types of interventions

Any technology aimed at creating a virtual environment/world, including immersive and/or non‐immersive VR of any intensity or duration, with the purpose of reducing acute pain intensity. These interventions may be used with or without pharmacological support. We included interventions that used any combination of input and output devices (e.g. mouse and shutter glasses; position tracker and head‐mounted display). For the intervention to be VR the participant must be actively interacting with the virtual environment which responds to their actions. We excluded interventions where the user was a passive observer, such as watching a virtually‐simulated movie as opposed to actively engaging in a virtual environment through physical movement.

Interventions of interest were:

1. VR distraction compared to no distraction;

2. VR distraction compared to non‐VR distraction;

3. VR distraction compared to other VR distraction (grouped by level of immersion which takes account of type of technical device, VR environment and level of user interaction).

Types of outcome measures

Primary outcomes

Acute pain intensity:

1. during the procedure, measured using:

behavioural measurements (observer‐report).

2. post‐procedure (up to one hour), measured using:

behavioural measurements (observer‐report).

Secondary outcomes

Adverse effects related to engagement with VR. These may include motion sickness, ocular problems (e.g. eye strain, blurred vision), balance disturbances, headaches, fatigue and repetitive strain injuries.

Child satisfaction with VR.

Child pain‐related distress, for example, self‐report, observer‐report or behavioural measurements of child distress, anxiety, fear and/or stress.

Parent anxiety using parent self‐reported anxiety scales or inventories.

Administration of rescue analgesia (i.e. administration of additional analgesic medications to treat acute pain not controlled by child's scheduled analgesic regimen).

Cost, which may include cost of the VR intervention or duration of child's treatment (measured in original currency).

Search methods for identification of studies

Electronic searches

With assistance from the Cochrane Pain, Palliative and Supportive Care (PaPaS) Review Group, we searched the following electronic databases up to October 2019.

The Cochrane Central Register of Controlled Trials (CENTRAL) via CRSO searched on 17/10/2019

MEDLINE (OvidSP) (1989 to 17 October 2019)

Embase (OvidSP) (1989 to 17 October 2019)

CINAHL (EbscoHOST) (1989 to 17 October 2019)

PsycINFO (Proquest) (1989 to 17 October 2019)

We used a combination of controlled vocabulary under the existing databases' organisational systems (e.g. MeSH and EMTREE) and free text terms. We did not apply language restrictions. Search dates start at 1989 as the intervention did not exist before this time. Please see the appendices for the search strategies and terms used for each of the databases: CENTRAL ( Appendix 1), MEDLINE ( Appendix 2), Embase ( Appendix 3), CINAHL ( Appendix 4), and PsycINFO ( Appendix 5).

Searching other resources

We searched for grey literature and ongoing trials using the following methods.

Proceedings from conferences

ProQuest Digital Dissertations and Theses

Index to Theses (Ireland and UK)

TrialsCentralTM (www.trialscentral.org)

Clinical trials register (Clinicaltrials.gov)

WHO Clinical Trial Search Portal (www.who.int/trialsearch)

Current Controlled Trials (www.controlled-trials.com)

We searched reference lists from retrieved eligible studies for other studies potentially eligible for inclusion. We handsearched relevant journals including Virtual Reality (from inception in 1995 to October 2019) and The International Journal of Virtual Realit y (from inception in 1998 to October 2019). We contacted experts in the field and authors of included studies about other potentially relevant studies.

Data collection and analysis

Selection of studies

Two review authors (VL, AM) independently assessed each title and abstract retrieved from the electronic searches for relevance using Covidence 2018. We resolved any discrepancies through discussion with a third review author (PB, PH or DD) acting as arbiter as required. We sourced and assessed the full paper if no abstract was available. We obtained and read full texts of the studies that potentially met our inclusion criteria. Two review authors (VL, AM) independently assessed these full texts against the inclusion criteria before a final decision regarding inclusion/exclusion was confirmed. We resolved any discrepancies by consensus or discussion with a third review author (PB, PH or DD) acting as arbiter where necessary. We listed all potentially relevant papers excluded from the review at full‐text stage in the Characteristics of excluded studies table, noting reasons for exclusion. We listed publications in abstract form only in excluded studies. We collated and reported multiple details of the same study/duplicate publications, to ensure that each study (rather than each report) was the unit of interest in the review. We used an adapted PRISMA flow chart to report the screening and selection process.

Data extraction and management

We designed, piloted and amended as necessary a data extraction form based on the Cochrane Pain, Palliative and Supportive Care Review Group template. Two review authors (VL, AM) independently extracted and managed data from each included RCT using the tailored data extraction form. Data extracted from included studies comprised of the following items.

Methods: aim of study, study design, method of participant recruitment, funding source, declaration of interests for primary investigators, statistical methods and consumer involvement.

Participants: description, participant inclusion and exclusion criteria, geographical location, setting, number, age, gender, ethnicity, principal and stage of diagnosis, type of procedure/treatment receiving.

Intervention: details of intervention (including aim, content, format, source, setting) and control/usual care, delivery of intervention (including timing, frequency, duration), providers of the intervention and intervention fidelity/integrity.

Outcomes: primary and secondary outcome measures (as detailed under Types of outcome measures), timing of assessment and methods of assessing outcome measures, follow up for non‐respondents and adverse events.

We resolved any discrepancies in data extraction between the two review authors through discussion or if required, consultation with a third review author (PB, PH or DD). The first review author (VL) entered the data into Review Manager 5 software ( RevMan 2014), with the second review author (AM) checking the accuracy of data entry. We attempted to obtain any missing, unclear or incomplete data by contacting the study authors.

Assessment of risk of bias in included studies

Two authors (VL, AM) independently assessed risk of bias for each study, using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions ( Higgins 2011). We resolved any disagreements by discussion and consensus with a third review author (DD) acting as arbiter as required. We completed a 'Risk of bias' table for each included study using the 'Risk of bias' tool in Review Manager 5.3 ( RevMan 2014). We assessed the following for each study.

Random sequence generation (checking for possible selection bias)

We assessed the method used to generate the allocation sequence for each included study as having:

For cross‐over studies we also assessed for period effects (i.e. systematic differences between responses in the second period compared to the first period not due to different interventions) as having:

For random sequence generation, studies assessed as high risk of bias were excluded.

Allocation concealment (checking for possible selection bias)

The method used to conceal allocation to interventions prior to assignment determines whether intervention allocation could have been foreseen in advance of assignmet, during recruitment, or changed after assignment.

We assessed the allocation concealment methods for each included study as having:

For allocation concealment, we excluded studies assessed as having high risk of bias.

Blinding of participants and personnel (checking for possible performance bias)

We assessed the methods used to blind study participants and personnel from knowledge of which intervention a participant received. We assessed methods as having:

Blinding of outcome assessment (checking for possible detection bias)

We assessed the methods used to blind study participants and outcome assessors from knowledge of which intervention a participant received. We assessed the methods as having:

For cross‐over studies we also assessed for carry‐over effects (i.e. effects of an intervention given in one period continue into a subsequent period, thereby interfering with the effects of the second intervention) as:

Incomplete outcome data (checking for possible attrition bias due to the amount, nature and handling of incomplete outcome data)

We assessed the methods used to deal with incomplete data as having:

Selective reporting (checking for reporting bias)

We assessed whether primary and secondary outcome measures were pre‐specified and whether these were consistent with those reported. We assessed the methods as having:

For cross‐over studies we also assessed for first period data on a basis of a test for carry‐over as having:

Size of study (checking for possible biases confounded by small size based on number of participants in each study arm)

We evaluated risk of bias for each included study according to the Cochrane PaPaS Review Group guidance on sample size based on the number of participants included in each study arm. We assessed studies to be at:

Other potential sources of bias

We assessed whether each trial was free of other problems that could put it at a risk of bias as having:

We had planned to also extend the risk of bias to include specific questions for cluster trials (e.g. selective recruitment of cluster participants; baseline reporting of comparability of clusters) ( Higgins 2011; Ryan 2011), but this was not necessary as we did not identify any cluster‐RCTs for inclusion in the review. We will address this in future updates if applicable.

Measures of treatment effect

We planned to analyze the data using RevMan 5.3 ( RevMan 2014). For dichotomous outcomes, we planned to report risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we planned to report mean differences (MD) (if outcomes were measured in the same way between trials) and 95% CI. For trials that used different methods to measure the same outcome, we planned to use standardized mean differences (SMD) and 95% CI. We planned to undertake a meta‐analysis if studies were sufficiently similar in design, population, interventions and outcomes, but this was not possible. We will undertake a meta‐analysis in future updates, should more data become available.

Unit of analysis issues

We acknowledged that issues could arise from the inclusion of cross‐over designs and cluster‐RCTs. We did not identify any eligible cluster‐RCTs. In future updates of this review, if we identify any cluster‐RCTs, we will use effect size estimates and standard errors, adjusted in the analysis for clustering, and combine the studies using the generic inverse‐variance method ( Higgins 2011). We will adjust sample sizes using the methods described in the Cochrane Handbook using an estimate of the intra‐cluster correlation co‐efficient (ICC) derived from the trial (if possible), from a similar trial or from a study of a similar population. If we use ICCs from other sources, we will report this and conduct sensitivity analyses to investigate the effect of variation in the ICC.

We identified one within‐subject (cross‐over) study as eligible for inclusion in the review. We analysed the data according to recommendations in the Cochrane Handbook ( Higgins 2011) for cross‐over trials. We used the effect estimate and standard deviation based on a paired t‐test. If we identify additional cross‐over studies in future updates, we will combine the studies using the generic inverse‐variance method ( Higgins 2011, section 16.4) and seek statistical advice for this part of the analysis.

Dealing with missing data

We contacted study authors for missing data. We noted levels of attrition in the included studies. We were unable to perform any meta‐analysis in this review due to clinical heterogeneity in population and procedural conditions. In future updates of this review, we will conduct analysis of outcomes on an intention‐to‐treat basis (i.e. by including all randomised participants in the group to which they were randomised regardless of whether or not they received the allocated intervention). Where this is not possible (i.e. data were not provided by study authors), we will conduct an analysis based on the number of participants for whom outcome data are known. As part of our 'Risk of bias' assessment, we reported the number of participants lost to follow‐up and the levels of, and reasons for, attrition in each trial. We had intended to investigate the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis; however, there were not enough data included in the review to conduct this analysis.

Assessment of heterogeneity

We considered whether studies were sufficiently similar (based on consideration of populations, interventions, settings or methodological features) to allow pooling of data using meta‐analysis and we assessed the degree of statistical heterogeneity by visual inspection of forest plots and by examining the Tau² (tau‐squared), I², and Chi² statistics. We regarded heterogeneity as substantial if:

the I² value was 50% or higher; and either

there was inconsistency between trials in direction or magnitude of effects (judged visually), or a low (P < 0.10) P value in the Chi² test for heterogeneity; or

the estimate of between‐study heterogeneity (Tau²) was above zero.

We had intended to investigate the presence of substantial heterogeneity using subgroup and sensitivity analyses however there were insufficient data included in the review to conduct these analyses. We did consider whether an overall summary was meaningful, and if it had been, we would have used a random‐effects analysis to produce it.

We detected substantial clinical heterogeneity across included studies and therefore do not report pooled results from meta‐analysis but instead provide a narrative description of data.

Assessment of reporting biases

We did not identify sufficient trials (at least 10) to evaluate reporting biases graphically using funnel plots. In future updates of this review, if 10 or more studies are included, we will conduct formal tests for funnel plot asymmetry; for continuous outcomes we will use the test proposed by Egger 1997, and for dichotomous outcomes we will use the test proposed by Harbord 2006. We will perform exploratory analyses if asymmetry is detected in any of these tests or is suggested by a visual assessment to investigate it. Where we suspect reporting bias we will attempt to contact study authors asking them to provide missing outcome data. Where this is not possible, and the missing data are thought to introduce serious bias, we will explore the impact of including such studies in the overall assessment of results by a sensitivity analysis.

Data synthesis

We planned to use a random‐effects model for meta‐analysis to produce a summary of effect based on the anticipated variability in the populations and interventions of included studies. However, we did not conduct meta‐analysis due to a lack of suitable studies. We judged that the heterogeneity in interventions and comparisons, participants, settings, and outcomes in our included studies would not contribute to meaningful conclusions from a statistically‐pooled result. Therefore, we present the data in additional tables ( Table 4 and Table 5 ), and narratively describe the results. Where possible we calculated effect estimates for each study using Review Manager 5.3 software ( RevMan 2014). In future updates of this review, if we identify enough studies suitable to be combined and undergo quantitative analysis, we will conduct meta‐analysis.

1

Study Measurement Tool Data VR Intervention Data No Distraction P value

Outcome: Acute pain intensity: self‐report (during the procedure)

Outcome: Acute pain intensity: behavioural measurement (observer‐report) (during the procedure)

Outcome: Acute pain intensity: self‐report (post‐procedure up to one hour)

Jeffs 2014
Adolescent Pediatric Pain Tool
(scale range 0 to 100; no pain to worst pain)

Between group difference
Difference: 9.7 mm, 95% CI: ‐9.5 to 28.9
VR group reported non‐statistical significant less procedural pain compared to no distraction group

P = 0.32

Mean (SD)
58.20 (31.7); N = 8

Mean (SD)
37 (31.80); N = 10

Nilsson 2009
Colour Analogue Scale
(scale range 0 to 10; 0 = no pain, 10 = most pain)

Mean (SD)
1.05 (1.74); N = 21

Mean (SD)
0.51 (0.99); N = 21

Outcome: Acute pain intensity: behavioural measurement (observer‐report) (post‐procedure up to one hour)

Nilsson 2009
Face, Legs, Activity, Cry, Consolability Scale
(total score out of maximum 10; higher score indicates pain)

Mean (SD)
0.29 (0.56); N = 21

Mean (SD)
0.19 (0.51); N = 21

Outcome: Child pain related distress (incl. anxiety, fear and distress)

Mean (SD)
During procedure (retrospective recording after procedure)
0.41 (0.29)

Mean (SD)
During procedure (retrospective recording after procedure)
0.47 (0.21)

2

Study Measurement Tool Data VR Intervention Data Non‐VR Distraction P Value

Outcome: Acute pain intensity: self‐report (during the procedure)

Outcome: Acute pain intensity: observer‐report (during the procedure)

Outcome: Acute pain intensity: behavioural measurements (observer‐report) (during the procedure)

Outcome: Acute pain intensity: self‐report (post‐procedure up to one hour)

Chan 2019
Emergency department

Faces Pain Scale‐Revised
(scale range 0 to 10; no pain to very much pain)

Between group difference: ‐1.78; 95% CI, ‐3.24 to ‐0.32

P = 0.018

Change in FPS‐R from baseline
‐1.39; 95% CI ‐2.42 to ‐0.36; N = 64

Change in FPS‐R from baseline
0.39; 95%CI ‐1.45 to 0.67; N = 59

VR intervention
P = 0.009
Non‐VR distraction
P = 0.47

Chan 2019
Outpatient pathology

Faces Pain Scale‐Revised
(scale range 0 to 10; no pain to very much pain)

Between group difference: ‐1.39; 95% CI, ‐2.68 to ‐0.11

P = 0.034

Change in FPS‐R from baseline
1.37; 95% CI, 0.50 to 2.23; N = 63

Change in FPS‐R from baseline
2.76; 95% CI, 1.79 to 3.72; N = 66

VR intervention
P = 0.003
Non‐VR distraction
P < 0.001

Jeffs 2014
Adolescent Pediatric Pain Tool
(scale range 0 to 100; higher score indicates more pain)

Between group difference
Difference: 23.7 mm, 95% CI: 2.4 to 45.0
VR group reported significant less procedural pain than PD group

P = 0.029

Means (SD)
After procedure
58.2 (31.7); N = 8

Means (SD)
After procedure
30.2 (29.2); N = 10

Walther‐Larsen 2019
Visual Analogue Scale
(scale range 0 to 100; higher scores indicates more pain)

Mean Difference 5; 95% CI, ‐3 to 13

P = 0.23

Median (IQR)
27 (8 to 33)

Median (IQR)
15 (5 to 30)

Outcome: Acute pain intensity: observer‐report (post‐procedure up to one hour)

Outcome: Acute pain intensity: behavioural measurements (observer‐report) (post‐procedure up to one hour)

Outcome: Adverse effects related to engagement with VR

Kipping 2012
Visual Analogue Scale
(scale range 0 to 10; 0 = no sick tummy (i.e., nausea), 10 = sick tummy as bad as it could possibly be)

Mean change scores
Nausea dressing removal (during procedure)
‐0.7 (1.1); N = 20
Nausea dressing application (after procedure)
‐0.3 (1.0); N = 20

Mean change scores
Nausea dressing removal (during procedure)
‐0.3 (1.5); N = 21
Nausea dressing application (after procedure)
‐0.5 (1.3); N = 21

P = 0.27
P = 0.65

Outcome: Administration of rescue analgesia

Kipping 2012
Frequency of rescue does of Entonox prescribed after commencement of procedure

Number (%)
3 (15%); N = 20

Number (%)
9 (43%); N = 21

P = 0.05

Certainty of the evidence

Two review authors (VL and AM) independently rated the certainty of evidence for each outcome. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to rank the certainty of the evidence using the GRADEprofiler Guideline Development Tool software (GRADEpro GDT 2015), and the guidelines provided in Chapter 12.2 of the Cochrane Handbook (Higgins 2011).

The GRADE approach uses five considerations (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the certainty of the body of evidence for each outcome. The GRADE system uses the following criteria for assigning grades of evidence:

high: we are very confident that the true effect lies close to the estimate of effect;

moderate: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different;

low: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect;

very low: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

We considered evidence from RCTs as high certainty but we downgraded the evidence by one (‐1) or two (‐2) where we identified:

serious (‐1) or very serious (‐2) limitation to study quality (risk of bias);

serious (‐1) or very serious (‐2) inconsistency across studies;

some (‐1) or major (‐ 2) uncertainty about directness of evidence;

serious (‐1) or very serious (‐2) imprecise data; and

high probability of the presence of publication bias (‐1).

We reported our judgement on the certainty of the evidence in the 'Summary of findings' tables.

'Summary of findings' table

We included three 'Summary of findings' tables:

1. VR distraction compared to no distraction;

2. VR distraction compared to non‐VR distraction;

3. VR distraction compared to other VR distraction.

We used the methods described in Chapter 11 of the Cochrane Handbook ( Schunemann 2011) to prepare the 'Summary of findings' tables. For each table, we presented the results for the primary outcomes of acute pain intensity self‐report, observer‐report and behavioural measurements (observer‐report) measured during procedure and up to one hour post‐procedure and the secondary outcome adverse effects, as outlined in the section on Types of outcome measures. As meta‐analysis was not possible in this review, we presented results in a narrative 'Summary of findings' table format. We used the GRADE system to judge the certainty of the evidence using GRADEprofiler software (GRADEpro GDT 2015).

Subgroup analysis and investigation of heterogeneity

We had planned to conduct the following subgroup analyses for the primary outcome:

(i) younger (0 to 9 years) versus older (10 to 18 years) aged children;

(ii) immersive versus non‐immersive VR interventions.

However, we did not do so because of a limited number of heterogeneous small trials for each intervention type and the fact that data were not reported separately for different ages. In future updates of this review, if sufficient data, we will conduct our planned subgroup analyses.

Sensitivity analysis

We had planned to conduct a sensitivity analysis based on trial quality but did not do so as we did not pool data statistically. In future updates of this review, if sufficient data are available, we will perform sensitivity analysis by separating high from low quality. We define 'high quality' as a trial having low risk of bias for sequence generation and adequate allocation concealment and low risk of bias for loss to follow up, classified as less than 10% for primary outcome data.

We will perform a sensitivity analysis for plausible variations in estimated intra‐cluster correlation coefficients (ICCs) if unit‐of‐analysis errors arise in future included cluster‐randomised trials and the ICCs had been estimated for those studies. We will limit sensitivity analyses to primary outcomes. We will conduct a sensitivity analysis to determine the influence of validated versus non‐validated scales on the effects of intervention on outcome.

Consumer participation

The editorial process of the Cochrane Pain, Palliative and Supportive Care Review Group included feedback on the review from one consumer referee in addition to health professionals. The first author of the review continues to engage in research in the field of children's health care and services with particular emphasis on the voice and visibility of children themselves. These child perspectives were drawn upon in the review, alongside children's perspectives of VR use in health care. We also obtained feedback from the consumer representative organisation Children in Hospital Ireland who recommended that for future trials it would be worth considering how children and young people are involved in the planning and design stage of the research as well as participants. Additionally, for future research it would be worth examining whether capacity/ability to understand/communicate or other aspects of a specific disability or condition would have an important influence on the effectiveness of the distraction stimulus.

Results

Description of studies

Results of the search

We identified 1827 citations in the database search and a further 19 citations through searching other resources. There were 1254 citations for screening after removal of duplicates. We excluded 1131 citations not meeting the review inclusion criteria on initial screening of titles and abstracts. We assessed 123 citations for eligibility at full‐text screening and excluded 70 citations (representing 65 studies) that did not meet the review selection criteria. Seventeen studies (reported in 18 citations) met the inclusion criteria and four studies (reported in five citations) are awaiting classification. Thirty studies (reported in 32 citations) are ongoing. See Figure 1 .

Risk of bias in included studies

We have summarised 'Risk of bias' results in Figure 2 and Figure 3 .

Other potential sources of bias

Effects of interventions

See: Table 1 ; Table 2 ; Table 3

Comparison 1: VR distraction compared to no distraction

Primary outcome: acute pain intensity

1. During the procedure

2. Post‐procedure (up to one hour)

Secondary outcomes

Adverse effects related to engagement with VR

Adverse effects related to VR were reported in five studies (154 participants; Atzori 2018; Gold 2006; Hoffman 2019; Jeffs 2014; Schmitt 2011).

Atzori 2018 assessed nausea in both VR and no VR conditions using a Visual Analogue Scale (scale range 0 to 10; none to worst nausea). Gold 2006 used the Child Simulator Sickness Questionnaire to determine whether the child felt sick as a result of the intervention. Hoffman 2019 assessed nausea as a result of VR using a Graphic Rating Scale (scale range 0 to 10; no nausea to vomit). Jeffs 2014 did not report what measure was used to assess adverse effects. Schmitt 2011 used a Graphic Rating Scale (scale range 0 to 100; no nausea to severe nausea) to assess nausea in the VR condition.

Two studies (n = 38) reported no adverse effects ( Gold 2006; Jeffs 2014). One study ( Atzori 2018; n = 15) found evidence of no evidence of a difference for nausea levels between immersive VR and non‐VR distraction conditions. Hoffman 2019 (n = 48) reported that VR nausea was less than one on a 10 point scale. Schmitt 2011 (n = 53) reported some mild nausea symptoms in the VR treatment group.

We judged this to be very low‐certainty evidence, downgraded for serious study limitations, and very serious indirectness.

Child pain‐related distress (including anxiety, fear and/or stress)

Child pain‐related distress was reported in three studies (198 participants; Chen 2019; Nilsson 2009; Wolitzky 2005). Chen 2019 used the Children Fear Scale (scale range 0 to 4; no fear to extreme fear). Nilsson 2009 used the Facial Affective Scale (FAS; scale range 0 to 1 from least to most distressed). Wolitzky 2005 used Visual Analogue Scales (scale range 0 to 100; none to maximum pain or anxiety) to report a composite distress score (i.e. mean of self‐report of anxiety and pain).

Chen 2019 found evidence of a beneficial effect of immersive VR compared to no distraction for reducing child fear (MD ‐0.46, 95% CI ‐0.90 to ‐0.02). Nilsson 2009 found no evidence of a beneficial effect for non‐immersive VR compared to no distraction for reducing pain‐related distress (MD ‐0.06, 95% CI ‐0.21 to 0.09). Wolitzky 2005 found no evidence of a difference in distress between those receiving immersive VR and no distraction ( Table 4 ).

We judged this to be low‐certainty evidence, downgraded for serious study limitations, and serious indirectness.

Subgroup analyses

We did not perform meta‐analysis on any data and were not able to conduct subgroup analyses on data for this comparison.

Sensitivity analyses

We did not perform meta‐analysis on any data and were not able to conduct sensitivity analyses on data for this comparison.

Comparison 2: VR distraction compared to non‐VR distraction

Primary outcome: acute pain intensity

1. During the procedure

2. Post‐procedure (up to one hour)

Secondary outcomes

Adverse effects related to engagement with VR

Adverse effects were reported in six studies (429 participants; Chan 2019 (two RCTs); Dumoulin 2019; Jeffs 2014; Kipping 2012; Walther‐Larsen 2019). Dumoulin 2019 assessed the side effects of VR immersion using a rating scale of how much nausea was experienced in the VR distraction group. Kipping 2012 used a Visual Analogue Scale (scale range 0 to 10; no sick tummy (i.e., nausea) to sick tummy as bad as it could possibly be) to measure nausea associated with VR simulator sickness. Four studies did not report what measure was used to monitor adverse effects related with VR ( Chan 2019 (two RCTs); Jeffs 2014; Walther‐Larsen 2019).

Three studies (n = 229) ( Chan 2019; one RCT pathology); Kipping 2012; Walther‐Larsen 2019) found no evidence of a difference between immersive VR and non‐VR distraction groups for adverse effects ( Table 5 ). Chan 2019 (one RCT emergency department; n = 123) reported that four participants in the non‐VR distraction group had adverse effects (i.e. dizziness, nausea, headache, vomiting) but there were no adverse effects in the VR distraction group. Dumoulin 2019 (n = 59) reported that the change in estimated cyber sickness before and after VR immersion was not significant ( Table 5 ). Jeffs 2014 (n = 18) reported that no participants in the VR group reported seizures, nausea or adverse motion effects.

We judged this to be very low‐certainty evidence, downgraded for serious study limitations, and very serious indirectness.

Child satisfaction with VR

This was reported in two studies (118 participants; Dumoulin 2019; Walther‐Larsen 2019). The two studies assessed child satisfaction using a Visual Analogue Scale (scale range 0 to 100; higher scores indicate higher satisfaction).

Dumoulin 2019 found no evidence of a beneficial effect of immersive VR compared with Child Life non‐VR distraction (MD 0.00, 95% CI ‐11.19 to 11.19) and evidence of a beneficial effect of immersive VR compared with TV non‐VR distraction (MD 18.43, 95% CI 7.54 to 29.32). Walther‐Larsen 2019 reported no evidence of a difference between immersive VR and non‐VR groups for satisfaction with distraction measures ( Table 5 ).

We judged this to be low‐certainty evidence, downgraded for serious study limitations, and serious indirectness.

Child pain‐related distress (including anxiety, fear and/or stress)

This was reported in three studies (311 participants; Chan 2019 (two RCTs); Dumoulin 2019). Chan 2019 measured child anxiety using a Visual Analogue Thermometer (scale range 0 to 10; no anxiety to most anxiety). Dumoulin 2019 measured child fear of pain using a Visual Analogue Scale (scale range 0‐100; from least to most fear).

Chan 2019 (for two RCTs) reported evidence of a between group difference in child self‐rated anxiety in the VR group compared to the non‐VR distraction group ( Table 5 ). Dumoulin 2019 found no evidence of a beneficial effect for immersive VR compared to TV (MD ‐15.67, 95% CI ‐32.78 to 1.44) and Child Life (Child Life; MD ‐9.58, 95% CI ‐29.34 to 10.18) non‐VR distraction.

We judged this to be very low‐certainty evidence, downgraded for serious study limitations, and very serious indirectness.

Administration of rescue analgesia

Administration of rescue analgesia was reported in one study (41 participants; Kipping 2012). The study measured frequency of rescue analgesia (i.e. Entonox doses prescribed after commencement of procedure) requirement. Less frequent administration of rescue analgesia was observed in the VR intervention group ( Table 5 ).

We judged this to be low‐certainty evidence, downgraded for serious study limitations and serious imprecision.

Subgroup analyses

We did not perform meta‐analysis on any data and were not able to conduct subgroup analyses on data for this comparison.

Sensitivity analyses

We did not perform meta‐analysis on any data and were not able to conduct sensitivity analyses on data for this comparison.

Comparison 3: VR distraction compared to other VR distraction

No studies reported this comparison ( Table 3 ).

Discussion

Summary of main results

The aim of this review was to assess the effectiveness and adverse effects of VR (immersive and non‐immersive) distraction interventions for reducing acute pain intensity in children (0 to 18 years) in any healthcare setting. We identified 17 studies with 1008 participants aged between four and 18 years undergoing treatments and procedures for intravenous puncture or port access, wound dressing changes, and physical therapy sessions.

The primary outcomes of the review were acute pain intensity (self‐report, observer‐report and behavioural measurement) assessed during and up to one‐hour post‐procedure. The secondary outcomes were adverse effects related to VR, child satisfaction with VR, child pain‐related distress, parent anxiety, administration of rescue analgesia and cost.

We aimed to include studies of VR distraction compared to no distraction, other non‐VR distraction and other VR distraction.

VR distraction compared to no distraction

For acute pain intensity during the procedure we found no evidence of an effect of VR (non‐immersive) for self‐reported pain compared to no distraction. No data were reported for observer‐reported pain. For behavioural measurement (observer‐reported) of pain we found inconsistent evidence of an effect of VR (immersive and non‐immersive).

For acute pain intensity up to one‐hour post‐procedure we found inconsistent evidence of an effect of VR (immersive, semi‐immersive and non‐immersive) for self‐reported pain compared to no distraction. For observer‐reported pain we found evidence of a beneficial effect of immersive VR compared to no distraction. For behavioural measurement (observer‐reported) of pain we found no evidence of an effect of VR (non‐immersive).

For secondary outcomes, there was insufficient and inconsistent evidence to draw a conclusion on adverse effects related to VR. We found inconsistent evidence of an effect of VR for child pain related distress. No studies assessed child satisfaction with VR, parent anxiety, administration of rescue analgesia, and cost.

The GRADE rating for all outcomes for VR distraction compared to no distraction indicated low to very low certainty of evidence meaning we have little confidence in the results. We downgraded the ratings due to serious limitations of study quality, serious or very serious indirectness; and for some outcomes very serious imprecision.

VR distraction compared to other non‐VR distraction

For acute pain intensity during the procedure we found inconsistent evidence of a beneficial effect favouring VR (immersive) for self‐reported and observer‐reported pain compared to other non‐VR distraction. For behavioural measurement (observer‐reported) of pain we found evidence of a beneficial effect for immersive VR compared to other non‐VR distraction.

For acute pain intensity up to one‐hour post‐procedure we found inconsistent evidence of an effect of VR (semi‐immersive and immersive) for self‐reported pain compared to other non‐VR distraction. For observer‐reported pain and behavioural measurement (observer‐reported) of pain we also found inconsistent evidence of an effect of VR (immersive) compared to other non‐VR distraction.

For secondary outcomes, there was insufficient evidence to draw a conclusion on adverse effects related to VR. We found inconsistent evidence of an effect of VR for child satisfaction with VR and for child pain related distress. One study reported less frequent administration of rescue analgesia in the VR intervention group. No studies assessed parent anxiety or cost.

The GRADE rating for all outcomes for VR distraction compared to other non‐VR distraction indicated low to very low certainty of evidence meaning we have little confidence in the results. We downgraded ratings due to serious limitations of study quality, and serious or very serious indirectness.

VR distraction compared to other VR interventions

We found no studies that reported this comparison.

Overall completeness and applicability of evidence

The limited, low‐ to very low‐certainty evidence in this review means that the review question remains incompletely answered. We were unable to draw conclusions about the effectiveness and adverse effects of VR distraction interventions, compared to no distraction, non‐VR distraction or other VR distraction, for children with acute pain in any healthcare setting. Included studies targeted children aged between four and 18 years undergoing needle‐related procedures for venipuncture, port access or intravenous placement; wound dressing procedures for chronic wounds and burns; and active‐assisted range‐of‐motion physical therapy sessions post burn injuries in specific inpatient and outpatient paediatric healthcare settings (i.e. burn units, oncology units, emergency departments, pathology/phlebotomy units, radiology and anaesthetic departments).

The clinical heterogeneity of the child participant populations in terms of age (i.e. seven to 17 years; four to 11 years; five to 16 years; eight to 17 years; seven to 12 years; eight to 12 years; six to 17 years; four to 16 years; 10 to 17 years; 11 to 17 years; five to 18 years; six to 18 years; seven to 16 years; and seven to 14 years) and variations in procedural and treatment conditions (i.e. venipuncture, port access, intravenous placement, wound dressings, physical therapy sessions) across the included studies made statistical pooling of data impossible. Most of the review primary outcomes were assessed by only a small number of studies with small sample sizes. The following secondary outcomes were not measured in any of the included studies: parent anxiety or cost. We found limited data for the remaining secondary outcomes of adverse effects related to VR, child pain‐related distress and administration of rescue analgesia; therefore, we can draw no conclusions related to these outcomes.

Quality of the evidence

We noted that a number of studies reported insufficient information about sequence generation and allocation concealment and we judged them to be at unclear risk of bias. We judged the majority of studies to be at high risk of bias for blinding participants and study personnel, and blinding of outcome assessment, because blinding did not take place, was broken, was not described but due to the nature of the intervention blinding was highly unlikely or was reported as not blinded, due to the nature of the intervention. We also judged a number of studies to be at high risk of bias for selective reporting and the majority of studies to be at high risk of bias for small sample sizes.

We used the GRADE approach to assess the certainty of the evidence. Across all comparisons and outcomes, we downgraded the certainty of evidence to low or very low due to serious study limitations (i.e. unclear risk of selection bias and high risk of performance and detection bias) and serious or very serious indirectness (i.e. differences in populations in terms of age, conditions and settings; differences in how the intervention was delivered; differences in comparisons and differences in the way outcomes were measured). We also downgraded some of the evidence for very serious imprecision (i.e. small sample size with wide 95% CI). Overall, this level of uncertainty makes it difficult to interpret the benefits or lack of benefits of VR distraction for acute pain in children.

Potential biases in the review process

We designed the methods of the review to minimise the introduction of additional bias. Extensive searches of the literature were performed and we attempted to contact authors for additional information as required. Two review authors independently completed data screening, data extraction, risk of bias and certainty of evidence rating. We acknowledge that such assessments involve subjective judgements. For any discrepancies, we reached consensus through consultation with the other authors.

Agreements and disagreements with other studies or reviews

Morris 2009 conducted a systematic review of the effectiveness of VR distraction in conjunction with pharmacologic analgesia, compared with pharmacologic analgesia alone or other forms of distraction, on reducing pain in both children and adults with burn injuries undergoing wound dressing changes and physiotherapy management. Of nine included studies, three were specific to children; one was included in our review ( Das 2005) and two were excluded ( Chan 2007; Hoffman 2000).

Garrett 2014 undertook a rapid evidence review of the effectiveness of VR therapy in pain management in both children and adults undergoing a variety of clinical procedures. Of the included child specific studies, Gold 2006, Kipping 2012, Schmitt 2011, and Wolitzky 2005 are included in our review and Gershon 2004, Chan 2007, and Steele 2003 were excluded because they did not meet the review eligibility criteria. The authors conclude that there is conflicting and limited evidence available and, similar to this current review's conclusions, highlight the need for further studies with greater scientific rigour to establish a better evidence base for VR distraction interventions for acute pain management.

In a meta‐analysis of the effectiveness of VR distraction for reducing pain in children and adults in experimental (e.g. cold pressor, finger pressure) and clinical (e.g. IV placement, burn wound dressings) conditions (14 controlled studies) Kenney 2016 included five studies with child populations; four of which were included in our review ( Gold 2006; Jeffs 2014; Kipping 2012; Wolitzky 2005) and one was excluded ( Gershon 2004). In the review, Kenney 2016 calculated a pooled effect size within each study for each indicator of pain (i.e. intensity, unpleasantness, and threshold). The results suggest that VR distraction is more effective when used with adults than with children; however, the majority of included studies with adults involved experimentally‐induced pain and it is difficult to draw comparisons here with pain experienced by children when undergoing clinical procedures and treatments.

In another recent systematic review and meta‐analysis on the effectiveness of VR distraction on pain in paediatric patients undergoing medical procedures (14 studies), Eijlers 2019 conclude that VR is more effective than usual care indicating a clinical benefit however the heterogeneity of study effects was high (I² = 93.3%); as a consequence of outlying and low‐quality studies, and the different medical procedures. Eijlers 2019 further conclude that it is hard to differentiate the benefit of VR over other forms of non‐VR distraction (e.g. watching television), and no distraction, because usual care is often not well defined. Eight of these studies were included in our review ( Das 2005; Gold 2006; Gerceker 2018; Hua 2015; Jeffs 2014; Kipping 2012; Schmitt 2011; Wolitzky 2005); we did not deem it appropriate to pool data statistically in this current review due to the clinical heterogeneity of the child participant populations and variations in procedural/treatment conditions across the included studies.

Collectively, these reviews, similar to the current review's conclusions, suggest that evidence is limited and of the evidence that does exist it is of low certainty and very low certainty from a small number of studies, and therefore we cannot be confident in the results. As the majority of review/meta‐analysis authors agree, more high certainty evidence with large sample sizes is needed before we can draw conclusions and consider VR distraction as a potential treatment for consistently reducing acute pain intensity in children. This supports the Birnie 2018 Cochrane systematic review of psychological interventions for needle‐related procedural pain and distress in children and adolescents. The review identified evidence supporting the efficacy of distraction, hypnosis, combined cognitive behavioural therapy and breathing interventions for reducing children's needle related pain and distress. The quality of the trials and overall evidence remains low to very low underscoring the need for improved methodological rigour and trial reporting.

Authors' conclusions

For children with acute pain

There is very little evidence for the use of VR technology in reducing pain in children. We found low‐ to very low‐certainty evidence of the benefit of VR distraction compared to no distraction or non‐VR distraction for the reduction of acute pain intensity in children (0‐18 years) undergoing clinical treatments and procedures. We found limited data to draw any conclusions about secondary outcomes including VR side‐effects, satisfaction with VR, pain‐related distress and administration of rescue analgesia. No studies assessed parent anxiety or cost. We have very little confidence in the evidence. Future well‐designed large high‐quality trials are likely to have an important impact on our confidence in the results.

For clinicians

There is very little evidence for the use of VR technology in reducing pain in children. We found low‐ to very low‐certainty evidence of the effectiveness of VR distraction interventions in reducing acute pain intensity in children to facilitate clinicians making informed evidence based decisions regarding treatment. We found limited data for adverse effects related to VR and other secondary outcomes including child satisfaction with VR, child pain‐related distress and rescue analgesia, therefore, we can draw no conclusions. No studies assessed parent anxiety or cost. We do not have any estimates on cost for these VR distraction interventions yet. More evidence is needed before VR distraction could be considered a potential treatment for consistently reducing acute pain intensity in children.

For policy makers and funders of the intervention

There is very little evidence for the use of VR technology in reducing pain and distress. The results of this review highlight that there is low‐ to very low‐certainty evidence of the benefit of VR distraction interventions for children with acute pain undergoing clinical procedures in healthcare settings. We found limited data for adverse effects related to VR, child satisfaction with VR, child pain related‐distress and administration of rescue analgesia. Parent anxiety was not assessed in any studies and we found no evidence on the cost or cost‐effectiveness of VR distraction interventions. There is insufficient evidence to recommend or refute the use of VR distraction interventions and more funding is needed to establish the evidence base in this area. Prioritising research calls in the area of children's pain will be critical to leveraging funding to enable large consortiums of researchers, VR developers, industry/SMEs, health care providers, and care recipients (i.e. children and their family) to conduct large high‐quality clinical trials in the future to establish an evidence base for VR distraction for acute pain in children.

General implications

We conclude, based on the 17 studies included in this review, that there is low‐ to very low‐certainty evidence for the use of VR distraction interventions for children with acute pain undergoing clinical procedures. Larger high‐quality studies to confirm the effectiveness and adverse effects of VR distraction interventions for children with acute pain in any healthcare setting are needed. While the 30 ongoing studies may contribute to future updates of this review, it is important that future trials use standardized age groups, such as those recommended by the US National Institute of Child Health and Human Development, to enhance consistency in reporting age‐related data for paediatric trials ( Williams 2012). This would improve the potential for data synthesis, enable exploration of age group variation and similarity regarding treatment response and safety and enable recommendations to be tailored to specific age groups ( Williams 2012). This is important in identifying which actual intervention is most effective for whom recognising that age and developmental stage may influence how pain and VR is experienced ( Kortesluoma 2006; Won 2017). Another avenue for future research is to see if VR is beneficial for children with chronic pain. Chronic pain is different from acute pain and consequently the function of distraction in these contexts may also differ (i.e. adaptive in acute procedural pain versus potentially maladaptive in chronic pain) ( Becker 2018).

Design

Large (i.e. at least 200 participants per arm) high‐quality randomised controlled trials, with cost‐effectiveness analyses, are needed to determine the effectiveness and adverse effects of VR distraction interventions for children with acute pain. Future research should compare VR with other types of widely accessible technological distractions (i.e. smart phones, iPads, tablets, apps); other types of reality such as augmented reality (i.e. virtual experience created by superimposing a virtual image within the real environment) and other types of VR using different VR environments (e.g. off‐the‐shelf pre‐existing virtual content versus customised content created for specific clinical purposes/procedures). Future research should give greater attention to children's preference regarding distraction and whether child characteristics such as temperament have an important influence on the effectiveness of the distraction stimulus ( Koller 2012; MacLaren 2007). Future trials also need to establish the effectiveness of VR across a variety of clinical experiences with different pain intensities and distress‐levels experienced by children, including for example, pain caused by diagnosed illness and associated treatments (e.g. renal or urinary diseases and inflammatory conditions); pain caused by medical and diagnostic procedures and fundamental nursing (e.g. post‐operative treatment, bone marrow procedures and spinal cord injections, side‐effects of medications); and pain caused by accidents (e.g. resetting of fractures or dislocation, suturing and removal of stitches) ( Kortesluoma 2004; Kortesluoma 2006). Also specific to future cross‐over trials, investigators should use the Consolidated Standards of Reporting Trials (CONSORT) statement extended to crossover trials to improve reporting of randomised crossover trials; thereby assisting researchers in extracting data for systematic reviews and in judging the reliability and validity of trial findings ( Dwan 2019).

Measurement (endpoints)

Future large high‐quality trials using a standardized approach to measuring and reporting similar outcomes across studies are likely to have an influence on the ability to compare and pool data. A specific implication of this review is the need for future trial investigators to use core outcome domains for paediatric acute pain clinical trials such as those developed by McGrath 2008 (i.e. pain intensity, global judgement of satisfaction with treatment, symptoms and adverse effects, physical recovery, emotional response and economic factors); in addition to using recommended validated pain outcome measures (self‐report and observational) that take account of children's different developmental abilities across different age groups ( Stinson 2006; von Baeyer 2007).

Also, specific to future VR trials, investigators should consider other mechanisms advanced in VR effectiveness for children with acute pain including the assessment of immersion and presence of the child in the VR environment ( Won 2017). For example, the ITC‐Sense of Presence Inventory offers researchers using a range of media systems a tool to measure, post exposure, four facets of a media experience related to presence; including sense of physical space, engagement, ecological validity and negative effects ( Lessister 2001).

History

Protocol first published: Issue 8, 2013
Review first published: Issue 10, 2020

Acknowledgements

We thank the Cochrane Consumers and Communication Group for their support in developing and publishing the protocol (2013) before the title was moved to the Pain, Palliative and Supportive Care Review Group (2017).

We thank the editors and staff of the Cochrane Pain, Palliative and Supportive Care Review Group for their support with the review specifically Anna Erskine, Kerry Harding, Andrew Moore and Phil Wiffen.

We would like to thank Information Specialists Joanne Abbott (Cochrane Pain, Palliative and Supportive Care Review Group) for running updated searches and John Kis‐Rigo (Cochrane Consumers and Communication Review Group) for providing assistance with our search strategy and running initial searches.

We would like to thank the peer reviewers of the full review: Walter J. Meyer, Kathryn Birnie, Tam Watson.

We would like to thank Anna Gunning, CEO, Children in Hospital Ireland for providing consumer participation feedback on the review.

Cochrane Review Group funding acknowledgement: this project was funded by the National Institute for Health Research (NIHR) via Cochrane Infrastructure funding to the Cochrane Pain, Palliative and Supportive Care Review Group (PaPaS). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Characteristics of studies awaiting classification [ordered by study ID]

Characteristics of ongoing studies [ordered by study ID]

Differences between protocol and review

1. To avoid confusion and for clarity purposes we removed the word 'simulation' from the title and throughout the review and instead use the term 'distraction.' We revised the review title and objective to conform to the standard format recommended by PaPaS, and to reflect changes to the scope of this review.

2. We moved the first two paragraphs of the section 'why is it important to do this review' to the 'description of the condition' section to highlight the high prevalence and negative consequences of poorly managed pain in children to describe the condition. Other changes to background sections included updating and changing order of references and updating the definition of pain.

3. We refined types of participants to children with acute pain. We removed chronic pain because it is different from acute pain and the function of distraction in these contexts may also differ. Primary and secondary outcomes in our protocol were heavily focused on acute pain.

4. We refined types of intervention, and comparisons, to the following: VR distraction compared to no distraction; VR distraction compared to other non‐VR distraction; and VR distraction compared to other VR distraction to more accurately reflect the focus on distraction.

5. We split the primary outcome of 'child pain' to separate pain outcomes for different reporters of pain (i.e. self‐report, observer‐report and behavioural measurement) acknowledging that different reporters can under‐ or over‐estimate pain intensity in children ( Brudvik 2016; Garcia‐Munitis 2006); and also to take account of different time points of pain assessment during and post‐procedure for different reporters of pain.

6. We removed length of child's recovery time from the secondary outcome cost because of lack of clarity about how this might be costed for acute pain intensity in children.

7. Under selection of studies, we added that publications in abstract form only were not included in the review due to limited data but were listed as excluded studies.

8. We added extra details to assessing risk of bias by including the extra domain of size of study as recommended by PaPaS. We also added extra detail for assessing risk of bias in cross‐over studies.

9. We added more details on the methods for assessing certainty of the evidence and creating 'Summary of findings' tables using wording suggested by PaPaS.

10. The protocol stated that we would prepare a 'Summary of findings' table using the primary outcome child pain and the following secondary outcomes: child satisfaction with VR simulation, child pain‐related distress and parent anxiety. Due to a change in how we reported the primary outcome, we reported the following primary outcomes: acute pain intensity: self‐report (during the procedure); acute pain intensity: observer‐report (during the procedure); acute pain intensity: behavioural measurements (observer‐report) (during the procedure); acute pain intensity: self‐report (up to one hour post‐procedure); acute pain intensity: observer‐report (up to one hour post‐procedure); acute pain intensity: behavioural measurements (observer‐report) (up to one hour post‐procedure) and the secondary outcome of adverse effects instead.

11. Sensitivity analysis: we revised our definition of a 'high‐quality study' from less than 20% for primary outcome data to less than 10% to reflect what we stated in our methods section for risk of bias for incomplete outcome data.

Contributions of authors

Veronica Lambert (VL) contributed to the design of the protocol and the instigation of the review, screened and selected studies, appraised the quality of and extracted data from selected papers, entered data, analyzed and interpreted the data and wrote the main review.

Patrick Boylan (PB) served as technical expert in relation to VR and contributed to decisions on inclusion where further consultation was required.

Lorraine Boran (LB) served as content expert in relation to pain and pain measurement and contributed to decisions where further clarifications were required.

Paula Hicks (PH) served as technical expert in relation to VR and contributed to decisions on inclusion where further consultation was required.

Richard Kirbakaran (RK) served as an experienced meta analytical statistician and contributed to discussions, clarifications and decisions specific to cross‐over trials.

Declan Devane (DD) served as methodological expert and advised on writing all stages of the protocol and review.

Anne Matthews (AM) provided expertise in conducting systematic reviews and assisted with study screening and selection, data extraction, quality appraisal, data entry, analysis and interpretation.

Declarations of interest

VL: None known.

PB: None known.

LB: None known.

PH: None known.

RK: None known.

DD: None known.

AM: None known.

References

References to studies included in this review

Chen 2019 {published and unpublished data}

Koushali 2017 {published data only}

References to studies excluded from this review

Babaie 2019 {published data only}

Brown 2014 {published data only}

Eijlers 2017 {published data only}

LeMay 2017a {unpublished data only}

References to studies awaiting assessment

NCH 2016 {unpublished data only}

References to ongoing studies

LeMay 2016b {unpublished data only}

Wong 2019 {unpublished data only}

Additional references

Birnie 2018

Birnie KA, Noel M, Chambers CT, Uman LS, Parker JA. Psychological interventions for needle-related procedural pain and distress in children and adolescents. Cochrane Database of Systematic Reviews 2018, Issue 10. Art. No: CD005179. [DOI: 10.1002/14651858.CD005179.pub4] [[PubMed] [CrossRef] PMC free article] [Google Scholar]

Covidence 2018 [Computer program]

Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org, 2018.

Hoffman 2011

Hoffman HG, Chambers G, Meyer W, Arceneaux LL, Russell W, Seibel E, et al. Virtual reality as an adjunctive non-pharmacologic analgesic for acute burn pain during medical procedures. Annals of Behavioral Medicine 2011;41(2):183-91. [PMC free article] [

# data[].attributes.attachment_link.title
Virtual reality distraction for acute pain in children

# data[].attributes.attachment_link.description
Cochrane Database Syst Rev. 2020; 2020(10): CD010686. Virtual reality (VR) computer technology creates a simulated environment, perceived as comparable to the real world, with which users can actively interact. The effectiveness of VR distraction on acute pain intensity in children is uncertain.