Jinhyung Kim1,2,3, Sang Baek Ryu4, Sung Eun Lee5,6, Jaewoo Shin1,2, Hyun Ho Jung2, Sung June Kim5,6,7, Kyung Hwan Kim4, Jin Woo Chang1,2. 1. Brain Korea 21 PLUS Project for Medical Science and Brain Research Institute and. 2. Department of Neurosurgery, Yonsei University College of Medicine, Seoul; 3. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea. 4. Department of Biomedical Engineering, College of Health Science, Yonsei University, Wonju; 5. School of Electrical Engineering and Computer Science. 6. Nano Bioelectronics and System Research Center, and. 7. Inter-University Semiconductor Research Center, Seoul National University, Seoul; and.
Abstract
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.
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.
Entities:
Keywords:
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
Authors: Martin Nüssel; Melanie Hamperl; Anna Maslarova; Shafqat R Chaudhry; Julia Köhn; Andreas Stadlbauer; Michael Buchfelder; Thomas Kinfe Journal: Pain Ther Date: 2020-12-16
Authors: Ruben Volkers; Esmay Giesen; Maudy van der Heiden; Mijke Kerperien; Sibylle Lange; Erkan Kurt; Robert van Dongen; Dennis Schutter; Kris C P Vissers; Dylan Henssen Journal: Neuromodulation Date: 2020-02-06