オバタ　ヒデアキ   OBATA Hideaki   小幡　英章    所属   埼玉医科大学  医学部 総合医療センター　麻酔科（麻酔科、産科麻酔科）    職種   教授
論文種別	学術雑誌(原著)
言語種別	英語
査読の有無	査読あり
表題	Dexmedetomidine decreases hyperalgesia in neuropathic pain by increasing acetylcholine in the spinal cord
掲載誌名	正式名：NEUROSCIENCE LETTERS ISSNコード：03043940
出版社	ELSEVIER IRELAND LTD
巻・号・頁	529(1),70-74頁
著者・共著者	Masafumi Kimura,Shigeru Saito,Hideaki Obata
発行年月	2012/10
概要	The activation of alpha 2-adrenoceptors has attracted attention as a therapeutic target for neuropathic pain, which remains a clinical challenge. In the present study, we examined the interaction between alpha 2-adrenergic and cholinergic signaling in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). Intrathecal administration of dexmedetomidine, which is a selective alpha 2-adrenoceptor agonist (0.1-1.0 mu g), dose-dependently suppressed hyperalgesia in SNL rats but did not alter paw withdrawal thresholds in normal rats. The analgesic effect of dexmedetomidine was abolished by intrathecal pretreatment with idazoxan (30 mu g) and atropine (30 mu g), which antagonize the alpha 2-adrenoreceptor and muscarinic receptor, respectively. In vivo microdialysis in the lumbar spinal dorsal horn revealed that acetylcholine concentrations increased after dexmedetomidine perfusion (1 mu M), but only in SNL rats. The combination of an ineffective dose of intrathecal dexmedetomidine with intraperitoneal donepezil, which is a cholinesterase inhibitor, decreased neuropathic hypersensitivity. These results suggest that plasticity of the spinal noradrenergic-cholinergic axis onl
DOI	10.1016/j.neulet.2012.08.008
PMID	22917606