465: Acute Virtual Reality Analgesic Response Predicts Long-Term Chronic Pain Outcomes

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary orofacial pain, Non-pharmacological treatments, Assessment and Measurement of Pain/Nociception, Treatment/management

Background and Aims: Virtual reality (VR) has been increasingly adopted as a non-pharmacological intervention for chronic pain. An early neuroimaging study suggested that VR-induced analgesia involves brain regions overlapping with those engaged in opioid-mediated pain modulation [1]. In addition, VR appears to enhance conditioned pain modulation (CPM) efficacy [2]. These findings suggest that VR-induced analgesia engages endogenous pain modulatory systems. Accordingly, we hypothesize that individual variability in VR responsiveness reflects the capacity of endogenous pain modulation. If so, responsiveness to a single VR session may predict longitudinal pain trajectories assessed via ecological momentary assessment (EMA) [3].

Methods: Forty-seven participants with chronic orofacial pain underwent one baseline in-person visit where experimental heat pain tolerance was assessed under three conditions: VR, Sham VR, and No VR (randomized order). Afterwards, participants completed a remote 180-day follow-up period during which their pain experience was measured twice-daily via EMA surveys. VR responsiveness was identified using permutation tests on repeatedly measured pain tolerance under the VR condition compared to baseline. Subsequently, we performed a linear mixed model to assess differences in daily pain reported by VR responders versus non-responders, with VR responsiveness as a fixed factor and baseline pain severity as a covariate.

Results: A significant main effect of condition on pain tolerance emerged (F_2,613.37=15.13, p<0.001). VR induced greater pain tolerance improvement (mean=0.61, SEM=0.23) than both Sham VR (mean=0.19, SEM=0.24, p<0.001) and No VR (mean=0.40, SEM=0.23, p=0.010). Permutation tests identified 19 VR responders and 28 non-responders. Notably, there was a main effect of responsiveness on EMA pain intensity (F_1,10771.16=196.59, p<0.001), with responders (mean=24.04, SEM=0.28) reporting lower pain than non-responders (mean=29.17, SEM=0.22). Similar patterns were observed for pain unpleasantness, mood, and anxiety.

Conclusions: We replicated our previous findings in healthy pain-free participants where VR with ocean content improved experimentally induced pain tolerance limits [4,5]. Importantly, in line with our hypothesis, we found that responsiveness to VR in the experimental acute setting predicts long-term pain-related outcomes. Our findings suggest that VR responsiveness could serve as a prognostic marker of a patient’s chronic pain course.

References: 1. Hoffman HG, Richards TL, Van Oostrom T, et al. The analgesic effects of opioids and immersive virtual reality distraction: evidence from subjective and functional brain imaging assessments. Anesthesia & analgesia. 2007;105(6):1776-1783.
2. Mehesz E, Karoui H, Strutton PH, Hughes SW. Exposure to an immersive virtual reality environment can modulate perceptual correlates of endogenous analgesia and central sensitization in healthy volunteers. The Journal of Pain. 2021;22(6):707-714.
3. May M, Junghaenel DU, Ono M, Stone AA, Schneider S. Ecological Momentary Assessment Methodology in Chronic Pain Research: A Systematic Review. J Pain. 2018;19(7):699-716.
4. Colloca L, Raghuraman N, Wang Y, et al. Virtual reality: physiological and behavioral mechanisms to increase individual pain tolerance limits. Pain. 2020;161(9):2010-2021.
5. Shafir R, Watson L, Felix RB, et al. Factors influencing the hypoalgesic effects of virtual reality. Pain. 2025:10.1097.

Presenting Author: Anna Han
Submitting Author: Anna Han

Senior Author: Luana Colloca

IASP 2026 Global Year theme of Neuropathic Pain: No

• Yang Wang: MS, PhD - University of Maryland, Baltimore School of Nursing
• Rachel L. Cundiff-O'Sullivan: MA, PhD - Washington University School of Medicine in St. Louis
• Luana Colloca: MS, MD, PhD - University of Maryland, Baltimore School of Nursing