Chronic pain remains poorly managed. The integration of immersive technologies (ie, virtual reality [VR]) with neuroscience-based principles may provide effective pain treatment by targeting cognitive and affective neural processes that maintain pain and therefore potentially changing neurobiological circuits associated with pain chronification and amplification. We tested the effectiveness of a novel VR neuroscience-based therapy (VRNT) to improve pain-related outcomes in n = 31 participants with chronic back pain, evaluated against usual care (waitlist control; n = 30) in a 2-arm randomized clinical trial ( NCT04468074) . We also conducted pre-treatment and post-treatment MRI to test whether VRNT affects brain networks previously linked to chronic pain and treatment effects. Compared with the control condition, VRNT led to significantly reduced pain intensity (g = 0.63) and pain interference (g = 0.84) at post-treatment vs pre-treatment, with effects persisting at 2-week follow-up. These improvements were partially mediated by reduced kinesiophobia and pain catastrophizing. Several secondary clinical outcomes were also improved by VRNT, including disability, quality of life, sleep, and fatigue. In addition, VRNT was associated with increases in dorsomedial prefrontal functional connectivity with the superior somatomotor, anterior prefrontal and visual cortices, and decreased white matter fractional anisotropy in the corpus callosum adjacent to the anterior cingulate, relative to the control condition. Thus, VRNT showed preliminary efficacy in significantly reducing pain and improving overall functioning, possibly through changes in somatosensory and prefrontal brain networks.

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