Abstract:Objective:To investigate the changes of toll-like receptor 4 expression and its downstream cytokines TNF-α, IL-1β in the spinal cord in rat chronic constriction injury (CCI) models, and to discuss the potential target for treatment of neuropathic pain.Methods: Neuropathic pain was produced by CCI of right sciatic nerve as described previously.On the 1st , 3rd, 7th and 14th day after surgery, the expression of TLR4 mRNA and protein in L4-L6 was assessed by RT-PCR and Western blotting, respectively; the distribution of TLR4 in the spinal cord was detected by immunofluorescence.The levels of TNF-α, IL-1β in the spinal cord were detected by ELISA.Thermal and mechanical nociceptive thresholds were assessed with paw withdrawal latency to radiant heat and von Frey filaments.Rats receive sham operation served as controls.Results: The mechanical allodynia and thermal hyperalgesia were induced in animals after CCI.The paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) of right paw were decreased after CCI (P<0.05), and the expression of TLR4 mRNA and protein was significantly increased (P<0.05); the levels of TNF-α and IL-1β in SF were also significantly increased after CCI compared with that in the sham control (P<0.05).Conclusion: CCI-induced toll-like receptor 4 activation may increase the expression of cytokines and subsequently decrease pain threshold, indicating that TLR4 might be a potential target for the treatment of neuropathic pain.