5-HT2C receptor agonists attenuate pain-related behaviour in a rat model of trigeminal neuropathic pain

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• 作者：Kunihiro Nakai ; Aya Nakae ; Sosuke Oba ; Takashi Mashimo ; Koichi Ueda
• 关键词：Infraorbital nerve ; Trigeminal nerve ; 5-HT2C receptor ; Orofacial neuropathic pain ; Nerve injury
• 刊名：European Journal of Pain
• 出版年：2010
• 出版时间：November 2010
• 年：2010
• 卷：14
• 期：10
• 页码：999-1006
• 全文大小：578 K

文摘

Peripheral branches of the trigeminal nerve may be damaged during maxillofacial injury or surgical procedures and trigeminal trauma may induce severe pain that is very challenging to treat. Chronic constriction injury to the infraorbital nerve (ION-CCI) by loose ligatures has proven a useful model for some types of trigeminal neuropathic pain disorder. Using ION-CCI rats, we examined the antiallodynic effects of intrathecally administered agents which are selective for 5-HT2C receptors. Allodynia was evaluated by applying von Frey filaments to skin innervated by the injured ION. Dose-dependent antiallodynic effects followed administration of three 5-HT2C receptor agonists, 6-chloro-2-(1-piperazinyl)-pyrazine (MK212: 10, 30, and 100 μg); (S)-2-(chloro-5-fluoro-indol-l-yl)-1-methyamine fumarate (RO 60-0175: 10, 30, and 100 μg); (AaR)-8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino[1,2-a]quinoxalin-5(6H)-one (WAY-161503: 10, 30, and 100 μg). ED50 values for antiallodynic effects of MK212, RO 60-0175, and WAY-161503 were 39.62, 46.67, and 51.22 μg, respectively. Intrathecal administration of the 5-HT2C receptor antagonist, 8-[5-2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4,5]decane-2,4-dione (RS-102221: 30 μg) did not alter the mechanical threshold. Intrathecal pretreatment with RS-102221 (10 and 30 μg) reduced the antiallodynic effects of the highest dose of 5-HT2C agonists. These results indicated that, in this rat model, the 5-HT2C receptor plays a role in spinal inhibition of trigeminal neuropathic pain.