Highlights
- •Virtual reality (VR) enhanced conditioned pain modulation (CPM) efficiency.
- •Sham VR exposure reduced CPM efficiency.
- •There was no effect of real or sham VR on acute pain thresholds.
- •Real and sham VR had no effect on pain ratings during the CPM conditioning period.
- •VR attenuated mechanical pain sensitivity in a human surrogate model of central sensitization.
Abstract
Virtual reality (VR) has been shown to produce analgesic effects during different
experimental and clinical pain states. Despite this, the top-down mechanisms are still
poorly understood. In this study, we examined the influence of both a real and sham
(ie, the same images in 2D) immersive arctic VR environment on conditioned pain modulation
(CPM) and in a human surrogate model of central sensitization in 38 healthy volunteers.
CPM and acute heat pain thresholds were assessed before and during VR/sham exposure
in the absence of any sensitization. In a follow-on study, we used the cutaneous high
frequency stimulation model of central sensitization and measured changes in mechanical
pain sensitivity in an area of heterotopic sensitization before and during VR/sham
exposure. There was an increase in CPM efficiency during the VR condition compared
to baseline (P < .01). In the sham condition, there was a decrease in CPM efficiency compared to
baseline (P < .01) and the real VR condition (P < .001). Neither real nor sham VR had any effect on pain ratings reported during
the conditioning period or on heat pain threshold. There was also an attenuation of
mechanical pain sensitivity during the VR condition indicating a lower sensitivity
compared to sham (P < .05). We conclude that exposure to an immersive VR environment has no effect over
acute pain thresholds but can modulate dynamic CPM responses and mechanical hypersensitivity
in healthy volunteers.
Perspective
This study has demonstrated that exposure to an immersive virtual reality environment
can modulate perceptual correlates of endogenous pain modulation and secondary hyperalgesia
in a human surrogate pain model. These results suggest that virtual reality could
provide a novel mechanism-driven analgesic strategy in patients with altered central
pain processing.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of PainAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Human experimental pain models in drug development: Translational pain research.Curr Opin Investig Drugs. 2007; 8: 41-53
- The effect of N-methyl-D-aspartate antagonist (ketamine) on single and repeated nociceptive stimuli: A placebo-controlled experimental human study.Anesth Analg. 1995; 81: 63-68
- Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera.J Pain. 2009; 10: 556-572
- Effects of dexmedetomidine on conditioned pain modulation in humans.Eur J Pain. 2012; 16: 1137-1147
- What do monoamines do in pain modulation?.Curr Opin Support Palliat Care. 2016; 10: 143-148
- Peripheral neuropathic pain: A mechanism-related organizing principle based on sensory profiles.Pain. 2017; 158: 261-272
- High frequency electrical stimulation induces a long-lasting enhancement of event-related potentials but does not change the perception elicited by intra-epidermal electrical stimuli delivered to the area of increased mechanical pinprick sensitivity.PLoS One. 2018; 13e0203365
- Long-term facilitation of nociceptive withdrawal reflexes following low-frequency conditioning electrical stimulation: A new model for central sensitization in humans.Eur J Pain. 2010; 14: 822-831
- Not an aspirin: No evidence for acute anti-nociception to laser-evoked pain after motor cortex rTMS in healthy humans.Brain Stimul. 2016; 9: 48-57
- Resolving the brainstem contributions to attentional analgesia.J Neurosci. 2017; 37: 2279-2291
- Activation of the descending pain modulatory system using cuff pressure algometry: Back translation from man to rat.Eur J Pain. 2020; 24: 1330-1338
- Self-administered skills-based virtual reality intervention for chronic pain: Randomized controlled pilot study.JMIR Form Res. 2020; 4: e17293
- Activation of the opioidergic descending pain control system underlies placebo analgesia.Neuron. 2009; 63: 533-543
- Direct evidence for spinal cord involvement in placebo analgesia.Science. 2009; 326: 404
- How expectations influence pain.Pain. 2018; 159: S3-S10
- High-definition transcranial direct current stimulation enhances conditioned pain modulation in healthy volunteers: A randomized trial.J Pain. 2016; 17: 600-605
- Expectancy effects on conditioned pain modulation are not influenced by Naloxone or Morphine.Ann Behav Med. 2016; 50: 497-505
- Enhanced pain modulation among triathletes: A possible explanation for their exceptional capabilities.Pain. 2013; 154: 2317-2323
- Capsaicin-sensitive C- and A-fibre nociceptors control long-term potentiation-like pain amplification in humans.Brain. 2015; 138: 2505-2520
- Cerebral analgesic response to nonsteroidal anti-inflammatory drug ibuprofen.Pain. 2015; 156: 1301-1310
- Virtual reality as an adjunctive non-pharmacologic analgesic for acute burn pain during medical procedures.Ann Behav Med. 2011; 41: 183-191
- Using FMRI to study the neural correlates of virtual reality analgesia.CNS Spectr. 2006; 11: 45-51
- Modulation of thermal pain-related brain activity with virtual reality: Evidence from fMRI.Neuroreport. 2004; 15: 1245-1248
- The analgesic effects of opioids and immersive virtual reality distraction: Evidence from subjective and functional brain imaging assessments.Anesth Analg. 2007; 105 (table of contents): 1776-1783
- Acute alcohol effects on conditioned pain modulation, but not temporal summation of pain.Pain. 2019; 160: 2063-2071
- Primary motor cortex transcranial direct current stimulation modulates temporal summation of the nociceptive withdrawal reflex in healthy subjects.Pain Med. 2019; 20: 1156-1165
- Intrathecal reboxetine suppresses evoked and ongoing neuropathic pain behaviours by restoring spinal noradrenergic inhibitory tone.Pain. 2015; 156: 328-334
- Frequency-dependent top-down modulation of temporal summation by anodal transcranial direct-current stimulation of the primary motor cortex in healthy adults.Eur J Pain. 2018; 22: 1494-1501
- Anodal transcranial direct current stimulation over the primary motor cortex attenuates capsaicin-induced dynamic mechanical allodynia and mechanical pain sensitivity in humans.Eur J Pain. 2020; 24: 1130-1137
- Attenuation of capsaicin-induced ongoing pain and secondary hyperalgesia during exposure to an immersive virtual reality environment.Pain Rep. 2019; 4: e790
- Virtual reality for persistent pain: A new direction for behavioral pain management.Pain. 2012; 153: 2163-2166
- Reliability of conditioned pain modulation: A systematic review.Pain. 2016; 157: 2410-2419
- Perceptual correlates of nociceptive long-term potentiation and long-term depression in humans.J Neurosci. 2004; 24: 964-971
- Pattern of neuropathic pain induced by topical capsaicin application in healthy subjects.Pain. 2015; 156: 405-414
- Combining ketamine and virtual reality pain control during severe burn wound care: One military and one civilian patient.Pain Med. 2011; 12: 673-678
- Reference data for quantitative sensory testing (QST): Refined stratification for age and a novel method for statistical comparison of group data.Pain. 2010; 151: 598-605
- Alterations in pro-nociceptive and anti-nociceptive mechanisms in patients with low back pain: A systematic review with meta-analysis.Pain. 2020; 161: 464-475
- Influence of ketamine and morphine on descending pain modulation in chronic pain patients: A randomized placebo-controlled cross-over proof-of-concept study.Br J Anaesth. 2013; 110: 1010-1016
- The effect of a mental stressor on conditioned pain modulation in healthy subjects.Scand J Pain. 2012; 3: 142-148
- Defective endogenous pain modulation in fibromyalgia: A meta-analysis of temporal summation and conditioned pain modulation paradigms.J Pain. 2018; 19: 819-836
- Presurgical assessment of temporal summation of pain predicts the development of chronic postoperative pain 12 months after total knee replacement.Pain. 2015; 156: 55-61
- Assessment of conditioned pain modulation in healthy participants and patients with chronic pain: Manifestations and implications for pain progression.Curr Opin Support Palliat Care. 2019; 13: 99-106
- Comparison of existing electrode designs for preferential activation of cutaneous nociceptors.J Neural Eng. 2020; 17036026
- Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values.Pain. 2006; 123: 231-243
- A highly cognitive demanding working memory task may prevent the development of nociceptive hypersensitivity.Pain. 2020; 161: 1459-1469
- Phase-locked and non-phase-locked EEG responses to pinprick stimulation before and after experimentally-induced secondary hyperalgesia.Clin Neurophysiol. 2017; 128: 1445-1456
- Central sensitization of mechanical nociceptive pathways is associated with a long-lasting increase of pinprick-evoked brain potentials.Front Hum Neurosci. 2016; 10: 531
- Pathophysiological mechanisms of neuropathic pain: Comparison of sensory phenotypes in patients and human surrogate pain models.Pain. 2018; 159: 1090-1102
- Exploration of the conditioning electrical stimulation frequencies for induction of long-term potentiation-like pain amplification in humans.Exp Brain Res. 2016; 234: 2479-2489
- Test-retest reliability of 10 Hz conditioning electrical stimulation inducing long-term potentiation (LTP)-like pain amplification in humans.PLoS One. 2016; 11e0161117
- Recommendations on practice of conditioned pain modulation (CPM) testing.Eur J Pain. 2015; 19: 805-806
- Prediction of chronic post-operative pain: Pre-operative DNIC testing identifies patients at risk.Pain. 2008; 138: 22-28
- Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy.Pain. 2012; 153: 1193-1198
Article info
Publication history
Published online: January 16, 2021
Accepted:
December 29,
2020
Received in revised form:
December 14,
2020
Received:
August 10,
2020
Footnotes
Funding: The research was funded via the Masters in Experimental Neuroscience programme at Imperial College London.
Conflicts of Interest: The authors have no conflict of interest.
Identification
Copyright
Crown Copyright © 2021 Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc.
