Abstract
High-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex for neuropathic pain has been shown to be effective, according to systematic reviews and therapeutic guidelines. However, our large, rigorous, investigator-initiated, registration-directed clinical trial failed to show a positive primary outcome, and its subgroup analysis suggested that the analgesic effect varied according to the site of pain. The aim of this study was to investigate the differences in analgesic effects of rTMS for neuropathic pain between different pain sites by reviewing our previous clinical trials. We included three clinical trials in this mini meta-analysis: a multicenter randomized controlled trial at seven hospitals (N = 64), an investigator-initiated registration-directed clinical trial at three hospitals (N = 142), and an exploratory clinical trial examining different stimulation parameters (N = 22). The primary efficacy endpoint (change in pain scale) was extracted for each patient group with pain in the face, upper limb, or lower limb, and a meta-analysis of the efficacy of active rTMS against sham stimulation was performed. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated for pain change using a random-effects model. The analgesic effect of rTMS for upper limb pain was favorable (SMD = −0.45, 95% CI: −0.77 to −0.13). In contrast, rTMS did not produce significant pain relief on lower limb pain (SMD = 0.04, 95% CI: −0.33 to 0.41) or face (SMD = −0.24, 95% CI: −1.59 to 1.12). In conclusion, these findings suggest that rTMS provides analgesic effects in patients with neuropathic pain in the upper limb, but not in the lower limb or face, under the conditions of previous clinical trials. Owing to the main limitation of small number of studies included, many aspects should be clarified by further research and high-quality studies in these patients.
Highlights
Migita et al (1995) reported the pain-relieving effects of repetitive transcranial magnetic stimulation in two patients with central neuropathic pain
We extracted randomized controlled trials (RCTs) of repetitive transcranial magnetic stimulation (rTMS) using the figure-of-8 coil for neuropathic pain, conducted at Osaka University Hospital as the main study institution, because this was the first attempt to review the analgesic effects at different pain sites
This study investigated the differences in analgesic effects of rTMS over the M1 using a figure-of-8 coil for neuropathic pain between pain sites
Summary
Migita et al (1995) reported the pain-relieving effects of repetitive transcranial magnetic stimulation (rTMS) in two patients with central neuropathic pain. Some studies have examined the effectiveness of rTMS in alleviating pain at different stimulation sites (Hirayama et al, 2006; Lefaucheur et al, 2006b; Jette et al, 2013; de Oliveira et al, 2014; Lindholm et al, 2015; Ayache et al, 2016; Nurmikko et al, 2016; André-Obadia et al, 2018; Galhardoni et al, 2019; Attal et al, 2021; Freigang et al, 2021; Ojala et al, 2021). We have reported that 5 HzrTMS to M1 relieved neuropathic pain, but that to the primary somatosensory cortex, premotor area, and supplementary motor area did not (Hirayama et al, 2006). Another study reported that the efficacy of rTMS for upper limb pain tended to be higher than that for lower limb pain (Hosomi et al, 2013). Considering our previous studies, we hypothesized that the pain relief effects of rTMS might differ, depending on the pain site
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