Motor cortex stimulation and neuropathic pain: how does motor cortex stimulation affect pain-signaling pathways?
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.
Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute and.|Department of Neurosurgery, Yonsei University College of Medicine, Seoul;|Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.
Jinhyung
J
Kim
Department of Biomedical Engineering, College of Health Science, Yonsei University, Wonju;
Sang Baek
SB
Ryu
School of Electrical Engineering and Computer Science.|Nano Bioelectronics and System Research Center, and.
Sung Eun
SE
Lee
Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute and.|Department of Neurosurgery, Yonsei University College of Medicine, Seoul;
Jaewoo
J
Shin
Department of Neurosurgery, Yonsei University College of Medicine, Seoul;
Hyun Ho
HH
Jung
School of Electrical Engineering and Computer Science.|Nano Bioelectronics and System Research Center, and.|Inter-University Semiconductor Research Center, Seoul National University, Seoul; and.
Sung June
SJ
Kim
Department of Biomedical Engineering, College of Health Science, Yonsei University, Wonju;
Kyung Hwan
KH
Kim
Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute and.|Department of Neurosurgery, Yonsei University College of Medicine, Seoul;
Jin Woo
JW
Chang
D000818:Animals; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D009044:Motor Cortex; D009437:Neuralgia / Q000209:etiology* / Q000628:therapy*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020651:Ventral Thalamic Nuclei
D016760:Proto-Oncogene Proteins c-fos; D012701:Serotonin
18F-FDG = 2-deoxy-[18F]fluoro-d-glucose; GABA = gamma-aminobutyric acid; LCP = liquid crystal polymer; MCS = motor cortex stimulation; PAG = periaqueductal gray; PBS = phosphate-buffered saline; ROI = region of interest; VPL = ventral posterolateral nucleus; ZI = zona incerta; artifact removal; electrophysiology; mPET = micro-PET; microPET; motor cortex stimulation; neuropathic pain; rat model