Effect of dexmedetomidine on expression of Toll-like receptor 4 and nuclear factor kappa B in spinal cord in a rat model of neuropathic pain

Objective To evaluate the effect of dexmedetornidine on the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) in the spinal cord in rats with neuropathic pain (NP).Methods One hundred and eight male Wistar rats,aged 6-8 weeks,weighing 180-220 g,were randomly assigned into 3 groups (n =36 each):sham operation group (group S),NP group and dexmedetomidine group (group D).NP was induced by chronic constrictive injury in anesthetized rats.Sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.In group S,the right sciatic nerves were exposed,but not ligated.Dexmedetomidine 50 μg/kg was injected intraperitoneally once a day from the onset of operation to one day before the rats were sacrificed in group D,while the equal volume of normal saline was injected in groups S and NP.Mechanical withdrawal threshold (MWT) and thermal pain threshold (TPT) were measured on the day before operation (T0) and 3,7,and 14 days after operation (T1-3).After measurement of pain threshold at T1,T2 and T3 after operation,the L4-6 segments of the spinal cord were removed for determination of the expres-sion of TLR4 and NF-κB mRNA (by RT-PCR) and the expression of TLR4 and NF-κB in spinal dorsal horn (by immuno-histochemistry).Results Compared with group S,MWT and TPT were significantly decreased and the expression of TLR4,NF-κB and TLR4 and NF-κB mRNA was up-regulated after operation in groups NP and D (P ＜ 0.05).Compared with group NP,TPT and MWT were significantly increased and the expression of TLR4,NF-κB,TLR4 mRNA and NF-κB mRNA was significantly down-regulated after operation in group D (P ＜ 0.05).Conclusion The mechanism by which dexmedetomidine attenuates NP in rats is related to inhibition of the expression of TLR4 and NF-κB in rat spinal cord. Key words: Dexmedetomidine ;  Neuralgia ;  Toll-like receptor 4 ;  NF-kappa B