Noninvasive Transcranial Magnetic Stimulation (TMS) in Chronic Refractory Pain: A Systematic Review

Efficacy and tolerance of pharmacological medications in chronic pain are limited. Therefore, repetitive transcranial magnetic stimulation (rTMS) is regarded as a secure therapeutic option for pain relief, and it was proven to produce an analgesic effect. A wide variety of stimulation parameters can influence its long-lasting antalgic effect. Defining the best stimulation protocol can afford greater uniformity and consistency for considering rTMS as a promising effective tool. We aimed to systematically review and evaluate the current literature on transcranial magnetic stimulation for patients suffering from chronic pain, assess its efficacy, and estimate the best stimulation protocol. The Screened and tested electronic databases comprised PubMed, Ovid Medline, Cochrane database library, and Google scholar from the year 2000 till 2018. The keywords utilizing search terms "Transcranial magnetic stimulation", "chronic pain", "neuropathic pain" were used to study all possible randomized clinical trials about the impact of transcranial magnetic stimulation on long-lasting pain. All articles were judged for the possibility of prejudice using the Cochrane risk of bias tool for data extraction. Search engines produced seventy applicable results. Twelve randomized controlled clinical trials were included involving 350 patients with focal and generalized chronic pain. An existing proof showed a null response of low-frequency rTMS stimulation, rTMS delivered to the dorsolateral prefrontal cortex in chronic pain patients. However, a witnessed pain-killing response was documented when applying active high- frequency TMS on the motor cortex M1 area compared to sham. Pain relief was detected for a short time following the application of active high-frequency motor cortex stimulation in nine clinical trials, and the long-lasting analgesic effect was proved. No side effects were mentioned for the technique. Repetitive TMS can produce clinically meaningful relief from chronic pain, despite positive results, heterogeneity among all studies preclude firm conclusions regarding the optimal target stimulation site and parameters. Further studies are required to minimize bias, enhance performance, and define the best brain stimulation conditions and qualifications to maximize its potency.