Potential Mechanisms Supporting the Value of Motor Cortex Stimulation to Treat Chronic Pain Syndromes

Abstract

Throughout the first years of the twenty-first century, neurotechnologies such as motor cortex stimulation (MCS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) have attracted scientific attention and been considered as potential tools to centrally modulate chronic pain, especially for those conditions more difficult to manage and refractory to all types of available pharmacological therapies. Interestingly, although the role of the motor cortex in pain has not been fully clarified, it is one of the cortical areas most commonly targeted by invasive and non-invasive neuromodulation technologies. Recent studies have provided significant advances concerning the establishment of the clinical effectiveness of primary MCS to treat different chronic pain syndromes. Concurrently, the neuromechanisms related to each method of primary motor cortex (M1) modulation have been unveiled. In this respect, the most consistent scientific evidence originates from MCS studies, which indicate the activation of top-down controls driven by M1 stimulation. This concept has also been applied to explain M1-TMS mechanisms. Nevertheless, activation of remote areas in the brain, including cortical and subcortical structures, has been reported with both invasive and non-invasive methods and the participation of major neurotransmitters (e.g., glutamate, GABA, and serotonin) as well as the release of endogenous opioids has been demonstrated. In this critical review, the putative mechanisms underlying the use of MCS to provide relief from chronic migraine and other types of chronic pain are discussed. Emphasis is placed on the most recent scientific evidence obtained from chronic pain research studies involving MCS and non-invasive neuromodulation methods (e.g., tDCS and TMS), which are analyzed comparatively.

Motor Cortex Neurostimulation Technologies for Chronic Post-stroke Pain: Implications of Tissue Damage on Stimulation Currents

“…The lower focality of TMS and tDCS, as compared to EBS, could make them less sensitive to relative mislocalizations around the targeted location. This difference could reconcile the relevance of our current findings with the fact that TMS and tDCS studies in perilesional stroke regions have generally reported beneficial therapeutic effects with potentially less variability than EBS studies (Lima and Fregni, 2008; O’Connell et al, 2014; Hosomi et al, 2015; DosSantos et al, 2016). …”

Challenges of differential placebo effects in contemporary medicine: The example of brain stimulation

“…66 More recent work has identified strong network connections between motor cortex and the peri-aqueductal gray (PAG), anterior cingulate cortex (ACC), and other critical pain matrix regions. 67 Proposed TMS neurophysiological mechanisms of action include activation of top-down pain inhibition pathways, 68 modulation of thalamocortical circuits 69 and changes in cortical excitability. 70 In addition to the treatment “specific” effects described above, rTMS for pain yields a particularly high placebo response.…”

Mental Health Comorbidities in Pediatric Chronic Pain: A Narrative Review of Epidemiology, Models, Neurobiological Mechanisms and Treatment

“…Thus far, rTMS has been shown to be an effective treatment for burning mouth syndrome [191], complex regional pain syndrome [192], fibromyalgia [193,194], neuropathic pain [195,196,197], depressive disorders [198] and to a lesser degree PTSD and other anxiety disorders [199,200]. It has been proposed to prevent or revert the ongoing maladaptive plasticity within the pain matrix [201], and modify opioidergic, glutamatergic, gamma-aminobutyric acidergic, and serotoninergic neurotransmissions [202]. The application of screening, implementation of early interventions at the individual and familial level (e.g., teaching coping mechanisms, parent sensitivity training), refining current intervention strategies, and the innovation of new, targeted therapies, holds promise for addressing and reducing these comorbidities.…”