title: Involvement of spinal microglia and interleukin-18 in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI.
abstract: Dexmedetomidine, a selective alpha 2-adrenoceptor (α2AR) agonist, has provided significant analgesia in neuropathic pain. However, its underlying molecular mechanism has not been fully elucidated. In the present study, we found that intrathecal administration of dexmedetomidine alleviated mechanical allodynia induced by chronic constriction injury (CCI), and pretreatment with BRL44408 significantly reversed the dexmedetomidine-induced anti-nociceptive effect. Western blotting revealed that dexmedetomidine reduced the activation of microglia and the upregulation of interleukin-18 (IL-18) protein expression in the ipsilateral lumbar spinal dorsal horn, while BRL44408 pretreatment significantly blocked these effects of dexmedetomidine. Immunocytochemistry/immunohistochemistry indicated that the α2A-adrenoceptor was localised to microglia in primary culture, and IL-18 predominantly colocalised with the microglial marker Iba-1 in the dorsal horn of the spinal cord. These results suggest that the IL-18 signalling pathway in microglia may be involved in the anti-nociceptive effect of dexmedetomidine in rats subjected to CCI.
authors.affiliation: Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Shuang-Shuang
authors.initials: SS
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Wei-Shi
authors.initials: WS
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Ya-Lan
authors.initials: YL
authors.lastname: Zhou
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Jia-Le
authors.initials: JL
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Yuan-Chang
authors.initials: YC
authors.lastname: Xiong
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai, China. Electronic address: pshhuaxu@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D003251:Constriction, Pathologic; D020927:Dexmedetomidine / Q000494:pharmacology* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020382:Interleukin-18 / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D017288:Pain Threshold; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014110:Touch
chemical_list: D018712:Analgesics, Non-Narcotic; D020382:Interleukin-18; D018341:Receptors, Adrenergic, alpha-2; D020927:Dexmedetomidine
keywords: Dexmedetomidine; IL-18; Microglia; Neuropathic pain