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	Peripheral Nerve Injury Reduces Analgesic Effects of Systemic Morphine via Spinal 5-Hydroxytryptamine 3 Receptors
掲載誌名	正式名：ANESTHESIOLOGY ISSNコード：00033022
出版社	LIPPINCOTT WILLIAMS&WILKINS
巻・号・頁	121(2),362-371頁
著者・共著者	Masafumi Kimura,Hideaki Obata,Shigeru Saito
発行年月	2014/08
概要	Background: Morphine produces powerful analgesic effects against acute pain, but it is not effective against neuropathic pain, and the mechanisms underlying this reduced efficacy remain unclear. Here, the authors compared the efficacy of systemic morphine between normal rats and rats with peripheral nerve injury, with a specific focus on descending serotonergic mechanisms.Methods: After L5 spinal nerve ligation injury, male Sprague-Dawley rats were subjected to behavioral testing, in vivo microdialysis of the spinal dorsal horn to determine serotonin (5-hydroxytryptamine [5-HT]) and noradrenaline release, and immunohistochemistry (n = 6 in each group).Results: Intraperitoneal administration of morphine (1, 3, or 10 mg/kg) produced analgesic effects in normal and spinal nerve ligation rats, but the effects were greater in normal rats (P< 0.001). Morphine increased 5-HT release (450 to 500% of the baseline), but not noradrenaline release, in the spinal dorsal horn via activation of serotonergic neurons in the rostral ventromedial medulla. Intrathecal pretreatment with ondansetron (3 g), a 5-HT3 receptor antagonist, or 5,7-dihydroxytryptamine creatinine sulfate (100 g), a select
DOI	10.1097/ALN.0000000000000324
PMID	24887968