【Abstract】 Objective To investigate the effects of intrathecal (IT) coadministration of morphine and gabapentin on the expression of Toll-like receptor 4 (TLR4) in spinal cord using a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR). Methods one hundred male Sprague dawley (SD) rats weighing 200～250g were randomly divided into 5 groups (n = 20): sham operation group (group S), group SMIR, group SMIR + IT morphine (group M), group SMIR + IT gabapentin (group G) and group SMIR + IT morphine and gabapentin (group M+G). The artificial cerebrospinal fluid (ACSF) 20μl was administered intrathecally at 30 min before operation and day 1～3 after operation in group S and group SMIR, respectively. Morphine 2.5μg, gabapentin 50μg and morphine 2.5μg + gabapentin 50μg were administered intrathecally at 30 min before operation and day 1～3 after operation in group M, group G and group M+G, respectively. The rat model of persistent postoperative pain evoked by SMIR was established according to the method described by Flatters. Pain behavior was assessed by paw mechanical withdraw threshold (MWT) to Electronic von Frey Anesthesiometer stimulation at 1 day before and day 3,7,12,22 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 with their preoperative values and corresponding values in group S, the MWT values in group SMIR, group M and group G were significantly decreased at d3, d7, d12 and d22 (P <0.05), and the expression of TLR4 protein in the spinal cord were significantly increased at d3, d7, d12 after operation (P <0.05), while no significant differences were showed among group SMIR, group M and group G. Compared with group SMIR, M and G, the value of MWT was significantly increased after d3, d7, d12 after operation (P <0.05), and the expression of TLR4 protein in the spinal cord was significantly decreased at d3, d7, d12 after operation in group M + G (P <0.05). Conclusion The analgesic effects of intrathecal coadministration of morphine and gabapentin may be related to the inhibition of spinal TLR4 expression in a rat model of persistent postoperative pain evoked by SMIR.