Sensory and cortical biomarkers unveil pain modulation mechanisms induced by targeted multisensory neurostimulation

Chronic neuropathic pain is a complex experience that poses a major challenge in personalized treatment. Identifying objective biomarkers of pain modulation is critical to validate emerging non-pharmacological therapies with reliable endpoints, overcoming the limitations of simplified subjective scales.

Here, we introduce a multimodal monitoring framework that integrates behavioral, sensory, and cortical assessments to provide a comprehensive evaluation of a multisensory neurostimulation treatment combining immersive VR with targeted neurostimulation (VR+tSTIM). We compared the effects of this intervention with an active control in 18 participants with chronic neuropathic pain over multiple days.

VR+tSTIM led to a clinically significant reduction in self-reported pain intensity. This reduction was accompanied by sensory measures, with participants in the VR+tSTIM group showing enhanced tactile acuity and improved proprioceptive accuracy, effects that did not appear in the control group. Treatment effectiveness was further associated with cortical EEG signatures of decreased gamma and delta power together with increased alpha power.

These findings identify potential sensory and cortical biomarkers associated with analgesia and suggest that pain relief in neuropathy may involve the modulation of both peripheral and central mechanisms. This comprehensive assessment paradigm establishes a foundation for the objective monitoring of treatment efficacy and advances the search for mechanistic biomarkers of pain modulation in clinical neuroengineering.

This study was approved by the Kantonale Ethikkommission Zürich (Nr. 2021-02258).