Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?

Abstract

N europathic pain is often severe, and it can afflict patients for their entire lifetime. It can be caused by direct damage to the nervous system, and by neuronal degeneration. 7,8 Patients with degenerative diseases such as Parkinson's disease or dementia may experience neuropathic pain as a complication. Many studies have found that neuropathic pain can be induced by indirect nerve damage, but the mechanisms have not yet been clearly established. 7,8,29 The symptoms of neuropathic pain differ among patients, making treatment difficult.31 Although many studies of neuropathic pain and its control have been conducted, the mechanisms behind neuropathic pain are still not clear.Motor cortex stimulation (MCS) is a treatment modality used to modulate neuropathic pain by electrical stimulation. It was introduced in 1991 by Tsubokawa et al. and has since been used in clinical practice.46,47 MCS has advantages for clinicians and patients: MCS is simpler and easier to implement for pain modulation than other surgical methods, such as direct nerve stimulation and neurectomy, and can be considered an alternative for pain control. Among the many modalities involving electrical obJective Neuropathic pain is often severe. Motor cortex stimulation (MCS) is used for alleviating neuropathic pain, but the mechanism of action is still unclear. This study aimed to understand the mechanism of action of MCS by investigating pain-signaling pathways, with the expectation that MCS would regulate both descending and ascending pathways. methods Neuropathic pain was induced in Sprague-Dawley rats. Surface electrodes for MCS were implanted in the rats. Tactile allodynia was measured by behavioral testing to determine the effect of MCS. For the pathway study, immunohistochemistry was performed to investigate changes in c-fos and serotonin expression; micro-positron emission tomography (mPET) scanning was performed to investigate changes of glucose uptake; and extracellular electrophysiological recordings were performed to demonstrate brain activity. results MCS was found to modulate c-fos and serotonin expression. In the mPET study, altered brain activity was observed in the striatum, thalamic area, and cerebellum. In the electrophysiological study, neuronal activity was increased by mechanical stimulation and suppressed by MCS. After elimination of artifacts, neuronal activity was demonstrated in the ventral posterolateral nucleus (VPL) during electrical stimulation. This neuronal activity was effectively suppressed by MCS. coNclusioNs This study demonstrated that MCS effectively attenuated neuropathic pain. MCS modulated ascending and descending pain pathways. It regulated neuropathic pain by affecting the striatum, periaqueductal gray, cerebellum, and thalamic area, which are thought to regulate the descending pathway. MCS also appeared to suppress activation of the VPL, which is part of the ascending pathway.

Invasive Motor Cortex Stimulation Influences Intracerebral Structures in Patients With Neuropathic Pain: An Activation Likelihood Estimation Meta-Analysis of Imaging Data

“…Functionally, this could possibly be explained by suppressed interhemispheric inhibition. In the cerebellum, glucose uptake was decreased by neuropathic pain and increased by iMCS . Another study using functional magnetic resonance imaging (fMRI) suggested significant lower blood oxygen level dependent (BOLD) responses in the primary somatosensory cortex (S1) and prefrontal cortex following noxious stimulation after iMCS .…”

Cyclization of Motor Cortex Stimulation for Neuropathic Pain: A Prospective, Randomized, Blinded Trial

“…Animal studies have demonstrated that MCS can increase increase opioid, serotonin, and dopamine levels in the central nervous system, implying the electro‐pharmacological effects of the stimulation . The generation and depletion of these key CNS molecules may serve as a possible model to explain the continued efficacy of the 15 min ON/15 min OFF cyclized setting compared to other settings with shorter “off” time intervals.…”

“…Motor cortex stimulation (MCS) is a neuromodulation therapy used for the treatment of neuropathic pain . MCS analgesia is believed to work by inhibiting pathologically upregulated thalamic sensory neurons and disinhibiting the periaqueductal gray via M1 antidromic modulation of thalamocortical pathways . Case series , retrospective cohort studies , open label trials , and prospective, randomized, double‐blinded trials have demonstrated the efficacy of MCS in the treatment of patients with neuropathic pain of heterogeneous etiologies.…”

Rostral Agranular Insular Cortex Lesion with Motor Cortex Stimulation Enhances Pain Modulation Effect on Neuropathic Pain Model

“…MCS was found to attenuate hyperactivity of thalamic neurons [5]. We have previously reported that MCS modulate pain-signaling pathways and suppress activation of the ventral posterolateral nucleus (VPL) [14]. The insular cortex, although not yet extensively explored, also showed clear involvement in pain perception through imaging studies using PET or fMRI.…”