PMID- 36602702 OWN - NLM STAT- MEDLINE DCOM- 20230307 LR - 20230307 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 60 IP - 4 DP - 2023 Apr TI - Spinal MCP-1 Contributes to Central Post-stroke Pain by Inducing Central Sensitization in Rats. PG - 2086-2098 LID - 10.1007/s12035-022-03184-9 [doi] AB - Central post-stroke pain (CPSP) is a highly refractory form of central neuropathic pain that has been poorly studied mechanistically. Recent observations have emphasized the critical role of the spinal dorsal horn in CPSP. However, the underlying mechanisms remain unclear. In this study, rats were subjected to thalamic hemorrhage to investigate the role of spinal monocyte chemoattractant protein-1 (MCP-1) and C-C motif chemokine receptor 2 (CCR2) in the development of CPSP. Immunohistochemical staining and ELISA were used to assess the expression changes of c-Fos, Iba-1, GFAP, MCP-1, and CCR2 in the dorsal horn of the lumbar spinal cord following thalamic hemorrhage, and the involvement of spinal MCP-1 in CPSP was examined by performing intrathecal anti-MCP-1 mAb injection to neutralize the spinal extracellular MCP-1. We demonstrated that intra-thalamic collagenase microinjection induced persistent bilateral mechanical pain hypersensitivity and facilitated the spontaneous pain behaviors evoked by intraplantar bee venom injection. Accompanying CPSP, the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn was significantly increased up to 28 days post-intra-thalamic collagenase microinjection. Intrathecal injection of minocycline and fluorocitrate dramatically reverses the bilateral mechanical pain hypersensitivity. Moreover, intra-thalamic collagenase microinjection dramatically induced the up-regulation of MCP-1 but had no effect on the expression of CCR2 in the bilateral lumbar spinal dorsal horn, and MCP-1 was primarily localized in the neuron. Intrathecal injection of anti-MCP-1 mAb was also able to reverse CPSP and reduce the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn. These findings indicated that spinal MCP-1 contributes to CPSP by mediating the activation of spinal neurons and glial cells following thalamic hemorrhage stroke, which may provide insights into pharmacologic treatment for CPSP. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Yang, Fei AU - Yang F AUID- ORCID: 0000-0002-6857-2967 AD - Department of Anesthesiology and Perioperative Medicine, Fuzong Clinical College/900th Hospital of the Joint Logistic Support Force, Fujian Medical University, Fuzhou, 350025, China. AD - Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, 350025, China. AD - Pain Research Institute, Fujian Medical University, Fuzhou, 350025, China. FAU - Jing, Jun-Jie AU - Jing JJ AD - Department of Neurosurgery, Fujian Children's Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350025, China. FAU - Fu, Si-Yin AU - Fu SY AD - Department of Anesthesiology and Perioperative Medicine, Fuzong Clinical College/900th Hospital of the Joint Logistic Support Force, Fujian Medical University, Fuzhou, 350025, China. AD - Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, 350025, China. FAU - Su, Xiu-Zhu AU - Su XZ AD - Department of Anesthesiology and Perioperative Medicine, Fuzong Clinical College/900th Hospital of the Joint Logistic Support Force, Fujian Medical University, Fuzhou, 350025, China. AD - Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, 350025, China. FAU - Zhong, Yu-Ling AU - Zhong YL AD - Department of Anesthesiology and Perioperative Medicine, Fuzong Clinical College/900th Hospital of the Joint Logistic Support Force, Fujian Medical University, Fuzhou, 350025, China. AD - Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, 350025, China. FAU - Chen, Dong-Sheng AU - Chen DS AD - Department of Anesthesiology and Perioperative Medicine, Fuzong Clinical College/900th Hospital of the Joint Logistic Support Force, Fujian Medical University, Fuzhou, 350025, China. cdsheng315@sohu.com. AD - Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, 350025, China. cdsheng315@sohu.com. FAU - Wu, Xiao-Zhi AU - Wu XZ AD - Department of Anesthesiology and Perioperative Medicine, Fuzong Clinical College/900th Hospital of the Joint Logistic Support Force, Fujian Medical University, Fuzhou, 350025, China. www7410@sohu.com. AD - Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, 350025, China. www7410@sohu.com. FAU - Zou, Yi-Qing AU - Zou YQ AD - Department of Anesthesiology and Perioperative Medicine, Fuzong Clinical College/900th Hospital of the Joint Logistic Support Force, Fujian Medical University, Fuzhou, 350025, China. yiqing51@163.com. AD - Department of Anesthesiology and Perioperative Medicine, Dongfang Hospital, Xiamen University, Fuzhou, 350025, China. yiqing51@163.com. LA - eng GR - 81801101/National Natural Science Foundation of China/ GR - 2020Y9043/Joint Funds for the Innovation of Science and Technology of Fujian Province/ GR - 2021J011264/Natural Science Foundation of Fujian Province of China/ GR - 2020J011130/Natural Science Foundation of Fujian Province of China/ GR - 2022J01490/Natural Science Foundation of Fujian Province of China/ GR - 20QNPY073/Army's Youth Cultivation Program/ PT - Journal Article DEP - 20230105 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Chemokine CCL2) SB - IM MH - Rats MH - Animals MH - *Chemokine CCL2/metabolism MH - Central Nervous System Sensitization MH - Rats, Sprague-Dawley MH - Hyperalgesia/metabolism MH - *Neuralgia/metabolism MH - Spinal Cord/metabolism MH - Spinal Cord Dorsal Horn/metabolism OTO - NOTNLM OT - Astrocyte OT - Central post-stroke pain OT - Central sensitization OT - MCP-1 OT - Microglia OT - Neuroinflammation OT - Spinal dorsal horn EDAT- 2023/01/06 06:00 MHDA- 2023/03/08 06:00 CRDT- 2023/01/05 11:19 PHST- 2022/09/07 00:00 [received] PHST- 2022/12/18 00:00 [accepted] PHST- 2023/01/06 06:00 [pubmed] PHST- 2023/03/08 06:00 [medline] PHST- 2023/01/05 11:19 [entrez] AID - 10.1007/s12035-022-03184-9 [pii] AID - 10.1007/s12035-022-03184-9 [doi] PST - ppublish SO - Mol Neurobiol. 2023 Apr;60(4):2086-2098. doi: 10.1007/s12035-022-03184-9. Epub 2023 Jan 5.