Analgesia-enhancing effects of repetitive transcranial magnetic stimulation on neuropathic pain after spinal cord injury: An fNIRS study

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for chronic intractable neuropathic pain in patients with spinal cord injury (SCI). However, the analgesia-enhancing effects of rTMS on conventional interventions (e.g., medications), and the underlying mechanisms remain poorly understood. Objective: To investigate the enhancement of analgesia and change of cortex activation by rTMS treatment on neuropathic pain following SCI. Methods: A double-blind, sham-controlled, clinical trial was performed. Twenty-one patients with neuropathic pain after SCI were randomized (2:1) to receive a session of rTMS (10 Hz, a total of 1200 pulses at an intensity of 80% resting motor threshold) or sham treatment over the left primary motor cortex (M1) corresponding to the hand area daily for six weeks with a one-day interval per week. At T0 (before rTMS treatment), T1 (after the first session rTMS), T2 (after one week), T3 (after two weeks), T4 (after four weeks) and T5 (after six weeks), activations in the bilateral M1, primary somatosensory cortex (S1), premotor cortex (PMC) and prefrontal cortex (PFC) during the handgrip task were measured using functional near-infrared spectroscopy (fNIRS). In addition, the numerical rating scale (NRS) was used to assess pain. Results: The pain intensity or activation in PFC, PMC, M1 or S1 was not remarkably changed at T1. Along with the time, the pain intensity gradually decreased in both the rTMS and sham groups. The real rTMS, compared with the sham, showed more pain relief from two weeks (T3) to six weeks (T5), and the activations of the motor-related areas M1 and PMC were remarkably suppressed. Conclusions: The findings of this preliminary study with a small patient sample suggest that the analgesia-enhancing effects of high-frequency rTMS might be related with the amelioration of M1 and PMC hypersensitivity, shedding light upon the clinical treatment of SCI-related neuropathic pain.