Transdural motor cortex stimulation reverses neuropathic pain in rats: A profile of neuronal activation

Abstract

Motor cortex stimulation (MCS) has been used to treat patients with neuropathic pain resistant to other therapeutic approaches; however, the mechanisms of pain control by MCS are still not clearly understood. We have demonstrated that MCS increases the nociceptive threshold of naive conscious rats, with opioid participation. In the present study, the effect of transdural MCS on neuropathic pain in rats subjected to chronic constriction injury of the sciatic nerve was investigated. In addition, the pattern of neuronal activation, evaluated by Fos and Zif268 immunolabel, was performed in the spinal cord and brain sites associated with the modulation of persistent pain. MCS reversed the mechanical hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation, Fos immunoreactivity (Fos-IR) decreased in the dorsal horn of the spinal cord and in the ventral posterior lateral and medial nuclei of the thalamus, when compared to animals with neuropathic pain. Furthermore, the MCS increased the Fos-IR in the periaqueductal gray, the anterior cingulate cortex and the central and basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for Fos, although no changes were observed for Zif268 in the anterior cingulate cortex and the central amygdaloid nucleus after MCS. The present findings suggest that MCS reverts neuropathic pain phenomena in rats, mimicking the effect observed in humans, through activation of the limbic and descending pain inhibitory systems. Further investigation of the mechanisms involved in this effect may contribute to the improvement of the clinical treatment of persistent pain.

Motor Cortex Stimulation Therapy for Relief of Central Post-Stroke Pain: A Retrospective Study with Neuropathic Pain Symptom Inventory

“…We observed a significant association between burning (superficial) spontaneous pain relief and effective results (based on the VAS score) in our study; thus, we believe that the pain relief mediated by MCS is the result of orthodromic activation of the corticofugal pathways and antidromic activation of thalamocortical pathways, and the substantia gelatinosa, which participates in the modulation of the whole pain and the burning pain, plays an important role in these procedures. This is consistent with Fonoff’s research in animal models [26-28]. There are some limitations in our study.…”

“…According to a study by Goto et al [25] using diffusion tensor imaging to examine the effectiveness of M1 rTMS for CPSP, preservation of thalamocortical and corticofugal motor tracts predicts treatment efficacy. In an animal model of neuropathic pain, Pagano et al [26] and Fonoff et al [27, 28] found that animals treated with MCS had a decrease in Fos and zif expression in the dorsal horn of the spinal cord (DHSC), and an increase in Fos and zif expression in the periaqueductal gray matter. The periaqueductal gray matter is a part of a descending pain suppressor pathway that projects to the DHSC via the rostral ventromedial medulla.…”

Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: A review

“…EMCS is thought to revert neuropathic pain phenomena through activation of the limbic and descending pain inhibitory systems, similar to that reported in experimental animals. 95 Implanted MCS seems to have an interesting potential with greater long-term efficacy, but larger comparative and controlled versus placebo clinical studies are required to confirm and validate previously published results. Moreover, further investigation of the mechanisms involved in this effect may improve the clinical treatment of persistent pain.…”

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

“…Dopamine and serotonin can attenuate neuropathic pain, ultimately suppressing the input signal evoked by painful stimulation. [12][13][14]28,34,35 We used isoflurane for anesthetizing the rats during mPET imaging. There are many controversies regarding the relationship between isoflurane and brain function.…”