# The Analgesic Enhancing Effects of Coupling M1 and PMC rTMS on Neuropathic Pain After Spinal Cord Injury: An fNIRS Study

## TL;DR

Combining rTMS on the motor cortex and premotor cortex improves pain relief for neuropathic pain after spinal cord injury more than using the motor cortex alone.

## Contribution

Demonstrates that coupling M1 and PMC rTMS provides greater analgesic effects than M1 rTMS alone for post-SCI neuropathic pain.

## Key findings

- The M1 + PMC group showed the most significant reduction in pain intensity compared to the M1 and sham groups.
- Left PMC oxyhemoglobin concentration changes correlated with pain improvement in NRS and SF-MPQ2 scores.
- Pain relief in the M1 + PMC group lasted from Weeks 1 to 6 with inhibited left M1 and PMC activation.

## Abstract

Repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) shows promise for treating neuropathic pain (NP) after spinal cord injury (SCI), but its efficacy remains limited. This study investigated whether combining rTMS on M1 with premotor cortex (PMC) could improve pain relief in SCI patients with NP.

Thirty‐nine subjects with NP post‐SCI were randomly assigned to three groups: M1 + PMC (10‐Hz rTMS on left M1 and PMC), M1 (10‐Hz rTMS on left M1), and sham. They underwent daily rTMS sessions for 4 weeks with 2 days off each week. Pain was assessed using the numerical rating scale (NRS) and the Short‐Form McGill Pain Questionnaire‐2 (SF‐MPQ2). Functional near‐infrared spectroscopy (fNIRS) measured activations in bilateral M1, PMC, and primary somatosensory cortex (S1) during a handgrip task.

Pain intensity gradually declined in the M1 + PMC, M1, and sham groups over time. Both the M1 and M1 + PMC groups experienced greater reductions in NRS scores compared to the sham group (p < 0.05), with the M1 + PMC group showing the most significant reduction (p < 0.05). The M1 + PMC group showed pain relief from Weeks 1 to 6, along with notable inhibition of left M1 and the left PMC activation. The decrease in the oxyhemoglobin (HbO) concentration in the left PMC is significantly positively correlated with the improvement of the NRS score (r = 0.607, p = 0.028) and SF‐MPQ2 (r = 0.595, p = 0.032), respectively.

High‐frequency rTMS targeting both left M1 and the left PMC is more effective for NP after SCI than targeting left M1 alone, indicating a synergistic benefit.

Trial Registration: Chinese Clinical Trials Registry: ChiCTR2000029024