Effect Of Dexmedetomidine On Activity Of PCREB,c-fos In A Rat Model Of Chronic Neuropathic Pain

Objective To investigate the effects of dexmedetomidine on the activity of CREB,c-fos in spinal dorsal horn in a rat model of chronic neuropathic pain（CNP）.Methods Fifty-four adult male wistar rats,6-8weeks of age,weighing180-220g,they can be divided into three groups by using random nembers table,each group of18:sham group（group S）; chronic constriction injury group（group C）and dexmedetomidine group（group D）.The animals were anesthetized with intraperitoneal10%chloral hydrate350mg/kg.Four ligatures were placed on right sciatic nerve at1mm intervals with4-0silk thread in group C and group D.In group D,Dex50μg/kg was injected intraperitoneally （IP）once a day starting from the end of operation until the animals were sacrificed. Paw withdrawal threshold to mechanical stimulation with von Frey filament（MWT）and paw withdrawal latency to thermal stimulation （TWL）were measured on the1st day before and the3rd,7th and14th day after operation. Animals of three groups were killed at each time points after the measurement of MWT and TWL.Their lumbar segments（L4₆）were removed for measuring the expression of pCREB,c-fos by immunohisto chemistry.Results CCI significantly decreased PWT and PWL, increased the expression of pCREB,c-fos at the3rd,7th and14th day in spinal dorsal horn in group C and group D compared with group S（P<0.05）; Intraperitoneal Injection Dex significantly attenuated CCI induced mechanical and thermal hyperalgesia in group D as compared with group C（P<0.05）; Dex IP further decreased pCREB,c-fos expression in group D compared with group C（P<0.05）; In group C and group D the mechanical and thermal pain threshold was significantly reduced at the3rd,7th and14th day after operation compared with before operation, and to a minimum at the7th day after operation （P<0.05）; Compared with the3rd day after operation, the expression of pCREB,c-fos in group C and group D was significantly increased at the7th and14th day after operation, and to the highest at the7th day after operation （P<0.05）.Conclusion Intraperitoneal injection DEX can reduce the chronic neuropathic pain in rat,the mechanism may probably related to inhibition the activity of CREB, c-fos in spinal dorsal horn.