ABSTRACT
Objective To investigate the effects of HO/CO pathway on inflammation cytokines in a rat model of incisional pain. Methods Thirty-six rats were executed to collect ipsilateral spinal cord tissues for HO-1 detection by Western blot assay, and cytokines tumor necrosis factor (TNF)-a, interleukin (IL)-1b, IL-6 and high mobility group box (HMGB)1 were detected by ELISA before and at 1, 4, 8, 12 and 24 h after establishing incisional pain model. Additionally, 36 rats without establishment of incisional pain model were used as control group. A total of 144 model rats of incisional pain were divided into incisional pain (IP) group, IP+hemin group (100 mg/kg hemin was injected by i.p. before operation), IP+Znpp-IX group (45μmoL/kg Znpp-IX was injected by i.p. before operation) and IP+CORM-2 group (10 mg/kg CORM-2 was injected by i.p. before operation). Values of paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were detected, and expressions of TNF-a, IL-1 b, IL-6 and HMGB1 were measured by ELISA before and at 1, 4, 8, 12 and 24 h after operation. Results Compared with pre-operation of incisional pain in rats, expression levels of HO-1 protein and cytokines TNF-a, IL-1 b, IL-6 and HMGB1 were increased at 1, 4, 8, 12 and 24 h after operation (P PWTL were decreased and cytokines TNF-α, IL-1β, IL-6 and HMGB1 were increased in IP+Znpp-IX group (P<0.05). Conclusion Incisional pain can increase the expression of HO-1, and HO-1/CO pathway exists the regulatory effect on inflammatory cytokines in the rat model of incisional pain.
ABSTRACT
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.