491: Neural Signatures of Virtual Reality Analgesia in Temporomandibular Disorder: A Randomized Trial

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary orofacial pain, Non-pharmacological treatments, Electrophysiology/Clinical neurophysiology (e.g. microneurography, EEG, MEG, OPMs, TMS) , Digital Health Technologies

Background and Aims: Temporomandibular disorder (TMD) is a chronic pain condition with 5–12% prevalence and a marked female predominance (1,2). Scalable, nonpharmacologic adjuvants can reduce reliance on medications, and mind–body interventions show moderate benefit in chronic pain (3,4). Virtual reality (VR) is a promising, low-cost approach, but mechanistic, rigorous studies are needed to accelerate translation. Resting-state EEG peak alpha frequency (PAF) reflects cortical excitability and information processing and is linked to pain reports and sensitivity (5,6). We aim to test whether at-home telehealth-delivered VR differentially affects daily pain and PAF synchronization compared with sham VR and no intervention in TMD.

Methods: Adults aged 18-65 years with chronic TMD (target N=78) completed a counterbalanced longitudinal crossover trial with three 1-month phases: active VR, sham VR, and no intervention (NCT06214923). Home telehealth delivery follows prior crossover work showing that VR reduces chronic pain (7) and modulates pain-related physiology (8). Daily EMA captured self-reported pain intensity, unpleasantness, mood, and anxiety throughout each phase. Resting EEG is recorded at baseline and after each phase, PAF is computed from frontal, central, and temporal electrodes as an excitability marker (9). Pain change is tested using linear mixed modeling, and changes in PAF using RM-ANOVA, adjusting for randomization.

Results: This is an ongoing trial with a target enrollment of 78 participants. To date, 50 TMD participants have been enrolled: 47 were randomized (3 ineligible). Preliminary analyses in n=10 showed no overall main effect of the intervention on pre–post pain intensity F(2, 204.104)=0.303, p=0.739. Pairwise comparisons indicated larger pain reductions for Active VR than for No Intervention (Mean Difference=3.632, p<0.001) and for Sham VR than for No Intervention (Mean Difference=2.194, p=0.001). RM-ANOVA of PAF across baseline and three phases showed a trend for Condition, F(3, 4)=3.411, p=0.053, across frontal, central, and temporal sites electrodes.

Conclusions: In this ongoing randomized crossover trial, preliminary findings suggest that telehealth-delivered VR may reduce pain intensity compared with no intervention. EEG results further indicate a trend toward condition-related differences in PAF across frontal, central, and temporal sites, consistent with VR potentially engaging cortical dynamics relevant to pain modulation. Together, these early clinical and neurophysiologic signals support the feasibility of combining daily symptom monitoring with repeated EEG to probe mechanisms of VR analgesia. We anticipate completing full-sample analyses in time for the conference, which will provide more precise estimates of clinical effects and the robustness of PAF differences across conditions.

References: 1. Ohrbach R, Greene C. Temporomandibular Disorders: Priorities for Research and Care. J Dent Res. Jul 2022;101(7):742-743. doi:10.1177/00220345211062047
2. Shaefer JR, Khawaja SN, Bavia PF. Sex, Gender, and Orofacial Pain. Dent Clin North Am. Oct 2018;62(4):665-682. doi:10.1016/j.cden.2018.06.001
3. Clark GT, Padilla M, Dionne R. Medication Treatment Efficacy and Chronic Orofacial Pain. Oral Maxillofac Surg Clin North Am. Aug 2016;28(3):409-21. doi:10.1016/j.coms.2016.03.011
4. Colloca L, Miller FG. Harnessing the placebo effect: the need for translational research. Philos Trans R Soc Lond B Biol Sci. Jun 27 2011;366(1572):1922-30. doi:10.1098/rstb.2010.0399
5. Furman AJ, Meeker TJ, Rietschel JC, et al. Cerebral peak alpha frequency predicts individual differences in pain sensitivity. Neuroimage. Feb 15 2018;167:203-210. doi:10.1016/j.neuroimage.2017.11.042
6. Kisler LB, Kim JA, Hemington KS, et al. Abnormal alpha band power in the dynamic pain connectome is a marker of chronic pain with a neuropathic component. Neuroimage Clin. 2020;26:102241. doi:10.1016/j.nicl.2020.102241
7. Colloca L, Han A, Massalee R, et al. Telehealth virtual reality intervention reduces chronic pain in a randomized crossover study. NPJ Digit Med. Apr 7 2025;8(1):192. doi:10.1038/s41746-025-01553-x
8. Colloca L, Raghuraman N, Wang Y, et al. Virtual reality: physiological and behavioral mechanisms to increase individual pain tolerance limits. Pain. Sep 1 2020;161(9):2010-2021. doi:10.1097/j.pain.0000000000001900
9. McLain NJ, Yani MS, Kutch JJ. Analytic consistency and neural correlates of peak alpha frequency in the study of pain. J Neurosci Methods. Feb 15 2022;368:109460. doi:10.1016/j.jneumeth.2021.109460

Presenting Author: Nandini Raghuraman, MS, PhD
Submitting Author: Nandini Raghuraman

Senior Author: Luana Colloca, MD, PhD, MS

IASP 2026 Global Year theme of Neuropathic Pain: No

• James Cottom - University of Maryland Baltimore School of Nursing
• Yang Wang: PhD - University of Maryland Baltimore School of Nursing