Department of Plastic & Reconstructive Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
Eur J Pain. 2010 Nov;14(10):999-1006. doi: 10.1016/j.ejpain.2010.04.008. Epub 2010 May 21.
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.
三叉神经的外周分支可能在颌面损伤或手术过程中受损，而三叉神经创伤可能会引起难以治疗的剧烈疼痛。通过松散的结扎物对眶下神经（ION-CCI）进行慢性缩窄性损伤已被证明是某些类型的三叉神经病理性疼痛障碍的有用模型。我们使用 ION-CCI 大鼠，研究了鞘内给予选择性 5-HT2C 受体的药物的抗痛觉过敏作用。通过向受伤的 ION 支配的皮肤施加 von Frey 纤维来评估痛觉过敏。在三种 5-HT2C 受体激动剂，6-氯-2-（1-哌嗪基）-吡嗪（MK212：10、30 和 100μg）；（S）-2-（氯-5-氟-吲哚-1-基）-1-甲胺富马酸盐（RO 60-0175：10、30 和 100μg）；（AaR）-8,9-二氯-2,3,4,4a-四氢-1H-吡嗪并[1,2-a]喹喔啉-5(6H)-酮（WAY-161503：10、30 和 100μg）给药后，观察到剂量依赖性的抗痛觉过敏作用。MK212、RO 60-0175 和 WAY-161503 的抗痛觉过敏作用的 ED50 值分别为 39.62、46.67 和 51.22μg。鞘内给予 5-HT2C 受体拮抗剂 8-[5-2,4-二甲氧基-5-（4-三氟甲基苯磺酰胺基）苯基-5-氧戊基]-1,3,8-三氮杂螺[4.5]癸烷-2,4-二酮（RS-102221：30μg）不会改变机械阈值。鞘内预先给予 RS-102221（10 和 30μg）可降低最高剂量 5-HT2C 激动剂的抗痛觉过敏作用。这些结果表明，在这种大鼠模型中，5-HT2C 受体在脊髓抑制三叉神经病理性疼痛中起作用。
