Effects of intrathecal coadministration of morphine and gabapentin on the expression of toll-like receptor 4 in spinal cord in persistent postoperative pain rats

Abstract

Objective To investigate the effects of intrathecal coadministration of morphine and gabapentin (GBP) on the expression of toll-like receptor 4 (TLR4) in spinal cord by using a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR).Methods one hundred male SD rats weighing 200 g-250g were randomly divided into 5 groups (n=20):sham operation group (group S),group SMIR,group SMIR + intrathecal morphine (group M),group SMIR+intrathecal GBP (group G) and group SMIR+intrathecal morphine and GBP (group M+G).The artificial cerebrospinal fluid (ACSF) 20 μl was administered intrathecally at 30 min before operation and 1 d-3 d after operation in group S and group SMIR,respectively.Morphine 2.5 μg,GBP 50 μg and morphine 2.5 μg+GBP 50 μg were administered intrathecally at 30 min before operation and 1 d-3 d 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 d before and 3,7,12,22 d 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 3,7,12 d and 22 d[the MWT values of postoperative 12 d were(54.9±7.7),(26.1±4.3),(30.9±4.1),(31.6±3.8) g](P＜0.05),and the expression of TLR4 protein in the spinal cord were significandy increased at 3,7,12 d after operation [the expression of TLR4 protein of postoperative 7 d were (22.4 ± 1.1),(73.9 ±5.6),(71.3 ±3.2),(70.4 ±4.5)] (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 were(49±6),(47±7),(43.8±2.9) g significantly increased after 3,7,12 d after operation(P＜0.05),and the expression of TLR4 protein in the spinal cord were (42.6±2.2),(56.8±3.0),(38.6±4.8) significantly decreased at 3,7,12 d after operation in group M+G (P＜0.05).Conclusions The analgesic effects of intrathecal coadministration of morphine and GBP may be related to the inhibition of spinal TLR4 expression in a rat model of persistent postoperative pain evoked by SMIR. Key words: Toll-like receptor 4; Postoperative pain; Morphine; Gabapentin; Spinal cord