Changes of Toll-like receptor 4 and its downstream cytokines in spinal cord of rat model of neuropathic pain

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(P0.05),and the expression of TLR4 mRNA and protein was significantly increased(P0.05);the levels of TNF-α and IL-1β in SF were also significantly increased after CCI compared with that in the sham control(P0.05).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.