title: ATP-sensitive potassium channels alleviate postoperative pain through JNK-dependent MCP-1 expression in spinal cord.
abstract: Although adenosine triphosphate-sensitive potassium (KATP) channels have been proven to be involved in regulating postoperative pain, the underlying mechanism remains to be investigated. In this study, we aimed to determine the role of spinal KATP channels in the control of mechanical hypersensitivity in a rat pain model, in which rats were subjected to skin/muscle incision and retraction (SMIR) surgery, as well as in LPS-stimulated astrocytes. The results showed that KATP channel subunits Kir6.1, SUR1 and SUR2 were normally expressed in the spinal cord and significantly downregulated after SMIR. SMIR caused a marked increase in monocyte chemoattractant protein-1 (MCP-1) mRNA expression and in the protein level of p-JNK in the spinal cord. Intrathecal administration of a KATP channel opener pinacidil (Pina) suppressed mechanical allodynia after SMIR and significantly downregulated the MCP-1 mRNA expression and the protein level of p-JNK induced by SMIR. Inverted fluorescence microscopy showed that Kir6.1 was co-localized with astrocytes only and SUR2 was co-localized primarily with neurons, in a small amount with astrocytes. Furthermore, in vitro studies showed that following incubation with LPS, the astrocytic MCP-1 mRNA expression and p-JNK content were markedly increased, whereas the mRNA levels of Kir6.1 and SUR2 were significantly downregulated in astrocytes. KATP channel opener pinacidil inhibited the LPS-triggered MCP-1 and p-JNK elevation in rat primary astrocytes. The results suggested that KATP channel opener treatment is an effective therapy for postoperative pain in animals, through the activation of the JNK/MCP-1 pathway in astrocytes.
authors: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors: Xiang
authors: X
authors: Zhu
authors: Department of Anesthesiology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China.
authors: Jinqian
authors: J
authors: Liu
authors: Institute of Nautical Medicine, Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors: Yongjing
authors: Y
authors: Gao
authors: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors: Su
authors: S
authors: Cao
authors: Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors: Shiren
authors: S
authors: Shen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D007278:Injections, Spinal; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D054086:KATP Channels / Q000819:agonists / Q000378:metabolism*; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D020110:Pinacidil / Q000008:administration & dosage; D021381:Protein Transport; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D064233:Sulfonylurea Receptors / Q000378:metabolism
chemical_list: C577512:Abcc9 protein, rat; D018932:Chemokine CCL2; D054086:KATP Channels; D064233:Sulfonylurea Receptors; C092520:uK-ATP-1 potassium channel; D020110:Pinacidil; D048031:JNK Mitogen-Activated Protein Kinases