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

Overview

1. Neuroengineering Laboratory, Department of Health Sciences and Technology, ETH Zürich,Tannenstrasse 1, 8092 Zürich, Switzerland
2. Center for Medical Physics and Biomedical Engineering, Medical University of Vienna,1090 Vienna, Austria
3. Department of Neurology and Neurophysiology and Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich,Zurich, Switzerland

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: This study was approved by the Kantonale Ethikkommission Zürich (Nr. 2021–02258).

Supplementary Information: The online version contains supplementary material available at 10.1186/s12984-026-01998-5.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

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Data availability

The datasets generated and/or analysed during the current study are not publicly available due restrictions related to participant privacy and institutional policies but all the completely anonymized data, code and materials used in the analysis are available from the corresponding author on reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 7 keywords, 12 MeSH terms, 1 funder, 82 references.

Cite

This paper

Aurucci, G. V., Gozzi, N., Cimolato, A., Wagner, M., Zipser, C. M., & Raspopovic, S. (2026). Sensory and cortical biomarkers unveil pain modulation mechanisms induced by targeted multisensory neurostimulation. Journal of neuroengineering and rehabilitation, 23(1), 194. https://doi.org/10.1186/s12984-026-01998-5

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