Can rTMS Reduce Chronic Neuropathic Pain?

Post by Lani Cupo

What's the science?

Pain is a vital signalling system for survival. However, when the nervous system sustains damage from physical trauma or is impacted by diseases such as diabetes and alcoholism, abnormal firing of nerves can lead to a form of chronic pain known as neuropathic pain. While common therapies include pharmacological interventions, noninvasive therapies such as repetitive transcranial magnetic stimulation (rTMS), where an electromagnetic pulse is applied outside the head, have been proposed as potential non-pharmacological treatments. Nevertheless, the potential benefits of the technique have not been well characterized in patients with neuropathic pain. This week in Brain, Attal and colleagues published the results of their randomized, double-blind, placebo-controlled trial on a large sample of patients with neuropathic pain, examining the effects of rTMS in two brain regions (primary motor cortex [M1] and dorsolateral prefrontal cortex [DLPFC]) on subjective measures of well-being. 

How did they do it?

rTMS is a technique that involves using a coil outside the skull to apply local, high-intensity electromagnetic pulses which can permeate to the brain’s cortex. These pulses produce electrical currents in neurons. In this experiment, 165 participants were randomized in terms of which brain region (M1 or DLPFC) would be stimulated and whether they would receive the active TMS or a placebo where both researchers and participants thought they were receiving the stimulation. The protocol for rTMS comprised several phases: first, 5 sessions over 5 consecutive days, followed by a 3 week period where participants received 1 session per week, a 6 week period where they received 1 session every 2 weeks, and finally a 12 week period where they received 1 session every 3 weeks for a total of 15 sessions over 22 weeks. To measure the impact on average pain, the authors administered a questionnaire (Brief Pain Inventory) to assess pain at baseline (the average scores of two timepoints before the first session of rTMS), immediately before each subsequent session, and 3 weeks after the final session. Additional metrics included self-report of pain from three additional questionnaires, pain journals, reports of anxiety and depression, and subjective reports of improvement from both the patients and the clinicians. The authors examined the difference between the four groups (M1-rTMS, M1-placebo, DLPFC-rTMS, DLPFC-placebo) accounting for variability between different clinics and multiple timepoint measurements. 

What did they find?

The authors found a significant difference between rTMS and placebo in the M1, with pain reduction increasing over time to significant levels after 8 sessions of rTMS. This implies that rTMS may be able to alleviate neuropathic pain, however, a single week of repeated sessions may not be sufficient to observe the benefits. In contrast, there was no significant impact of rTMS in the DLPFC when compared to placebo controls. A similar pattern was observed in the secondary outcomes, demonstrating the increased efficacy of rTMS in M1 compared with the DLPFC. Despite the positive effects, neither rTMS in the M1 or DLPFC improved outcome measures related to the quality of life, such as mood or sleep. Finally, it was observed that only a subset of the patients reported being “much” to “very much” improved following rTMS (<33%), and future research will investigate what factors determine which patients respond well to the treatment.

What's the impact?

This study is one of the first to investigate the impact of rTMS on neuropathic pain in a large sample of individuals with a double-blind, placebo-controlled study. The authors found that rTMS of the M1 was effective at reducing neuropathic pain. These findings suggest that therapies like rTMS could provide an alternative option for pain management that does not rely on potentially addictive pharmacological treatments.

Attal et al. Repetitive transcranial magnetic stimulation for neuropathic pain: a randomized multicentre sham-controlled trial. Brain (2021). Access the original scientific publication here.