Brain Stimulation
2026 Mar 30:103090. doi: 10.1016/j.brs.2026.103090. Online ahead of print.
Petru Isan , Patrick Mertens , Jean-Christophe Sol , Sylvain Fowo , François Vassal , Emile Simon , Yann Seznec , Geneviève Demarquay , Jean Jacques Lemaire , Xavier Moisset , Jerôme Coste , Yann Sühan Senova , Jean Pascal Lefaucheur , Stéphane Palfi , Joachim K Krauss, Assel Saryyeva, Clement Hamani, Erich Talamani Fonoff , Mounia Bouih , Michel Lanteri-Minet , Roland Peyron , Denys Fontaine
Abstract
Background: Motor cortex stimulation(MCS) has been used for over 30 years to treat refractory chronic neuropathic pain, but its efficacy, mechanisms of action, and the optimal electrode placement remain debated.
Objective: We retrospectively analyzed 100 patients treated with MCS across eight international centers to identify predictors of efficacy and optimal lead placement.
Methods: Active contacts were mapped to several Montreal Neurological Institute(MNI) space atlases. Patients were classified as responders(pain reduction ≥ two points, or > 50%) and non-responders. Logistic regression assessed relationships between clinical response and patient characteristics, stimulation parameters, contact coordinates, and atlas values.
Results: MCS induced greater mean pain reduction in responders than non-responders(2.6±2.5 vs. 0.9±1.3). Responders had lower stimulation voltage(3.5 vs. 4.7 V, p<0.0001), higher frequency(39.5 vs. 36.9 Hz, p=0.026) and narrower subarachnoid space(5.0 vs. 5.7 mm, p=0.023). We didn't observe a "sweet spot" for MCS analgesia and contacts were similarly distributed between groups over the sensory, motor and premotor regions. The relationship between somatotopy and efficacy was unclear. Pain relief was more likely when cortical areas rich in 90-100mm long projection fibers were stimulated.
Conclusions: These results challenge traditional MCS assumptions. Precise targeting of somatotopic regions may not be critical for pain relief, but our observations suggest that MCS modulates non-specific pain control centers, such as descending inhibitory pathways originating in the brainstem, via long projection fibers.
Keywords: CPSP; MCS; brain; electrode; neuromodulation; neuropathic; pain.
Copyright © 2026. Published by Elsevier Inc.
- PMID: 41921821
- DOI: 10.1016/j.brs.2026.103090

