Role of Toll-like receptor 4 in spinal cord in a rat model of persistent postoperative pain evoked by skin/ muscle incision and retraction

Objective To investigate the role of Toll-like receptor4 (TLR4) activation in spinal cord in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction(SMIR).Methods Ninetysix male SD rats weighing 200-250 g were randomly divided into 4 groups(n =24 each):group sham operation; group SMIR; group SMIR + IT scramble siRNA and group SMIR + IT TLR4siRNA.The rat model of persistent postoperative pain evoked by SMIR was established according to the method described by Flatters.The TLR4 siRNA were administered intrathecally for 7 days starting from 1 day beforc surgcry.Pain behavior was assessed by paw mechanical withdraw threshold (MWT) to Electronic von Frey Anesthesiometer stimulation at 1 day before and 1,3,7,12,and 22 days after operation.Four animals were sacrificed at each time point in each group for detection of the expression of TLR4 protein in the spinal cord by Western blot analysis.Results Compared to group sham group,MWT was significantly descreased at 3,7,12,and 22 days after operation,while the expression of TLR4 protein in the spinal cord were significantly increased at 3,7,12 days after operation in group SMIR and group SMIR + IT scramble siRNA ; IT TLR4siRNA significantly attenuated the hyperalgesia induced by SMIR and descreased the expression of TLR4 protein at 3,7,12 days after operation in group SMIR + IT TLR4siRNA.Conclusion TLR4 activation in spinal cord plays an important role in the development of SMIR-evoked persistent postoperative pain in rats. Key words: Toll-like receptor 4; Pain, postoperation; Spinal cord