Characterising the optimal pulse number and frequency for inducing analgesic effects with motor cortex rTMS

High- (≥5Hz), but not low-frequency (≤1Hz) rTMS (repetitive Transcranial Magnetic Stimulation) of the contralateral primary motor cortex (M1) can induce transient analgesic effects [5]. However, the impact of TMS frequency and pulse number remains poorly understood and may present an opportunity to optimise analgesic efficacy and promote long-term effects. Prior work indicated that a single session consisting of 2,000, but not 500 pulses of 10Hz rTMS, was necessary to induce a significant alleviation of neuropathic pain relative to sham stimulation [7]. At least 1000 pulses per session is recommended by the European Academy of Neurology, with the suggestion that increasing the pulse number may increase analgesic efficacy [2]. The most common dosage for chronic pain is 1000–2000 pulses per session, although up to 3000 pulses per session is cleared by the Food and Drug Administration (FDA) for treating major depression disorders. Regarding stimulation frequency, while 10Hz is most commonly employed in pain management, 20Hz M1-rTMS has also been demonstrated to be effective [4]. However, no direct comparison has been made between 10 and 20Hz rTMS.

Here we performed a single-blind, sham-controlled, crossover study to investigate the influence of pulse number and frequency on rTMS analgesia in a single session. Using cold pain threshold, we directly compared the analgesic efficacy of 3000 pulses with 1500 pulses of 10Hz rTMS over the M1 region. We also explored the analgesic influence of 3000 pulses of 20Hz rTMS. As session duration can affect rTMS analgesia [3], this third condition of 3000 pulses at 20Hz additionally balances pulse number and session duration. Before and after rTMS, we also assessed motor-evoked potential (MEP) amplitude for single pulse stimulation and long-interval cortical inhibition (LICI), to assess the impact of the differing rTMS doses on corticospinal excitability and GABAB mediated cortical inhibition. We hypothesised that 3000 pulses at 10Hz and 20Hz would achieve a better pain relief than 1500 pulses.