Dexmedetomidine blocks thermal hyperalgesia and spinal glial activation in rat model of monoarthritis  

作　　者：Bo XU Wei-shi ZHANG Jia-le YANG Hua XU Xiao-ming DENG Yu-qiu ZHANG 

机构地区：[1]Department of Anesthesiology, Changhai Hospital, The Second Military Medical University, Shanghai 200433, China [2]Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China

出　　处：《Acta Pharmacologica Sinica》2010年第5期523-530,共8页中国药理学报（英文版）

摘　　要：To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor （α2AR） agonist, on thermal hyperalgesia and spinal glial activation evoked by monoarthritis （MA）. Methods. MA was induced by an intra-articular injection of complete Freund＇s adjuvant （CFA）. Thermal hyperalgesia was measured by Hargreaves＇ test. The spinal glial activation status was analyzed by GFAP （an astrocytic marker） and Iba-1 （a microglial marker） immunohistochemistry or immunoblotting. Results： Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal （ip） injection of dexmedetomidine （2.5 and 10 μg/kg） was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 μg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post-MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed. Conclusion： Systemic dexmedetomidine inhibits the activation of spinal gila, which is possibly associated with its antihyperalgesia in monoarthritic rats.To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor （α2AR） agonist, on thermal hyperalgesia and spinal glial activation evoked by monoarthritis （MA）. Methods. MA was induced by an intra-articular injection of complete Freund＇s adjuvant （CFA）. Thermal hyperalgesia was measured by Hargreaves＇ test. The spinal glial activation status was analyzed by GFAP （an astrocytic marker） and Iba-1 （a microglial marker） immunohistochemistry or immunoblotting. Results： Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal （ip） injection of dexmedetomidine （2.5 and 10 μg/kg） was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 μg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post-MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed. Conclusion： Systemic dexmedetomidine inhibits the activation of spinal gila, which is possibly associated with its antihyperalgesia in monoarthritic rats.

关 键 词：pain modulation ARTHRITIS ASTROCYTE spinal cord rats alpha 2 adrenergic receptor DEXMEDETOMIDINE 

分 类 号：R[医药卫生]