Effect Of Dexmedetomidine On Expression Of Toll-like Receptor4and Nuclear Factor Kappa B In A Rat Model Of Chronic Neuropathic Pain

Objective:To investigate the effects of dexmedetomidine on toll-like receptor4（TLR4） and nuclear factor kappa B（NF-κB） expression in spinal dorsal horn in a rat model of chronic neuropathic pain（CNP）.Methods:One hundred and eight adult male wistar rats weighing180-220g were randomly divided into3groups （n=36each）:sham operation group（group S）; chronic constriction injury group（group NP） 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 NP 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 TLR4and NF-κB mRNA by reverse transcription-polymerase chain reaction（RT-PCR） and the expression of TLR4, NF-κB by immune-histochemistry.Results:CCI significantly decreased MWT and TWL, increased the expression of TLR4and NF-κB mRNA at the3rd,7th and14th day in spinal dorsal horn in group NP 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 NP（P<0.05）; Dex IP further decreased TLR4and NF-κB mRNA expression in group D compared with group NP（P<0.05）; In group NP 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 TLR4and NF-κB mRNA in group NP 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 TLR4and NF-κB expression in spinal dorsal horn.