Non-invasive Brain and Spinal Stimulation for Pain and Related Symptoms in Multiple Sclerosis: A Systematic Review

Abstract

Background: Neuropathic and nociceptive pain frequently affect patients with multiple sclerosis (MS), with a prevalence close to 90% and significant impact on general health and quality of life. Pharmacological strategies are widely used to treat pain in MS, but their effectiveness and side-effects are controversial. Among non-pharmacological treatments for pain, non-invasive brain and spinal stimulation (NIBSS) has shown promising preliminary results in MS.Objective: Systematic review to investigate the effect of NIBSS for the management of pain in MS.Methods: A literature search using Pubmed, Science Direct and Web of Science was conducted from databases inception to February 21, 2020 for studies assessing the analgesic effect of NIBSS on pain in MS.Results: A total of 279 records were title- and abstract-screened, nine were assessed for full text and included. The NIBSS techniques explored were transcranial direct current stimulation (N = 5), transcranial magnetic stimulation (N = 2), transcranial random noise stimulation (N =1), transcutaneous spinal direct current stimulation (N = 1). The targets were the primary motor cortex (M1; N = 4), the left dorsolateral pre-frontal cortex (DLPFC; N = 3), the spinal cord (N = 1), unspecified brain target (N = 1). The study designs were randomized (N = 7), open label (N = 1), single case report (N = 1). Despite the differences in study design, target and NIBSS technique that impeded a meta-analysis, all the studies converge in showing a significant improvement of pain after active NIBSS with less consistent effects on other symptoms of the pain-related cluster (depression, fatigue, cognition) and quality of life.Conclusions: Excitatory NIBSS over M1, left DLPFC and spinal cord appear to be the most effective protocols for pain in MS. Open questions include the use of neurophysiological or neuroimaging surrogate outcome measures, the stratification of patients according to the clinical profiles and underlying pathogenetic mechanisms and the combination of NIBSS to pharmacological treatment, neurorehabilitation, or psychotherapy to improve the clinical effect. The duration of the effect to NIBSS and the feasibility and efficacy of telemedicine NIBSS protocols are other open key questions.

Non-invasive brain stimulation therapy on neurological symptoms in patients with multiple sclerosis: A network meta analysis

“…Although the mechanisms of MS pain are not fully understood, descending pain modulatory system dysfunction has been linked to human chronic pain conditions ( 54 ). And in patients with MS, the processes of brain networks that mediate pain relief may be disrupted in part ( 55 ). Stimulation on M1 is supposed to induce analgesic effects through an antidromic top-down modulation of thalamo-cortical pathways ( 55 ).…”

“…And in patients with MS, the processes of brain networks that mediate pain relief may be disrupted in part ( 55 ). Stimulation on M1 is supposed to induce analgesic effects through an antidromic top-down modulation of thalamo-cortical pathways ( 55 ). In addition, previous study found that in healthy volunteers theta-burst stimulation (TBS) seemed more analgesic than high frequency repetitive transcranial magnetic stimulation and a higher number of pulses of prolonged continuous TBS might result in stronger analgesic effects ( 56 ).…”

Neuropathic Pain in Multiple Sclerosis and Its Animal Models: Focus on Mechanisms, Knowledge Gaps and Future Directions

“…With respect to the management of chronic pain, the challenge experienced in other pathological conditions associated with neuropathic pain, are also relevant to MS. Both pharmacological and non-pharmacological approaches are used, although further studies are needed to establish the effectiveness of these therapies ( 69 , 266 , 267 ). Importantly, the evaluation of pharmacological therapies in EAE or other models of MS, need to be performed in a manner that can be applicable in the clinic.…”

Review of the Treatments for Central Neuropathic Pain

“…While effective for many patients, invasive procedures introduce potential for complications as well as waning pain relief with time [ 60 , 61 , 62 ]. Many patients consider alternative interventional therapies either in lieu of or in combination with current standard options [ 63 , 64 , 65 ]. We therefore expand upon these options and their supporting evidence in the treatment of CNP below.…”

“…Such modalities include repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS) and cranial electrotherapy stimulation (CES) [ 63 , 66 ]. These methods have been applied to a range of CNP syndromes including CPSP, post-SCI pain, and MS [ 65 , 67 , 68 ], although the efficacy of these therapies remains under investigation in the management of neuropathic pain.…”