Neurophysiological and psychophysical mechanisms associated with immersive virtual reality-induced hypoalgesia: a...

Although growing evidence supports immersive virtual reality (IVR) as a nonpharmacological intervention for pain management, the mechanisms by which IVR induces hypoalgesia are still under debate. In this study, we review and evaluate candidate neurophysiological and psychophysical mechanisms underlying IVR-induced hypoalgesia and their experimental evidence. A preregistered systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing the databases Web of Science, Medline (through PubMed), SCOPUS, and APA PsycINFO. A total of 28 studies were included, involving 1142 participants (673 women [59%]). Of these, 78 (6.8%) experienced acute pain, 171 (15%) chronic pain, and 869 (76%) were exposed to experimental pain inductions. Risk-of-bias assessment ranged from low (n = 1; 3.5%), with some concerns (n = 16; 57.1%), to high (n = 11; 39.3%). The overall quality of studies ranged from fair (n = 6; 21.5%) to good (n = 21; 75%) to excellent (n = 1; 3.5%). Our synthesis suggests that IVR-induced hypoalgesia correlates with increased brain activity, specifically in nuclei implicated in descending pain modulation, and altered autonomic responses, specifically enhanced parasympathetic system activity. Similarly, IVR-induced hypoalgesia is associated with changes in psychophysical pain tests, such as increased pain tolerance and/or thresholds. However, caution is warranted when interpreting these results, as 89.3% of the studies assessed only the immediate effects of a single IVR session, and intervention protocols were highly heterogeneous. Furthermore, most studies tested pain-free subjects using experimentally induced pain (n = 20), limiting extrapolation to clinical populations. We conclude that experimental designs allowing causal inference-ideally through mediation analyses-are currently lacking and urgently needed to elucidate the mechanisms underlying IVR-induced hypoalgesia.