Effects Of Oxycodone Hydrochloride On Expression Of P-NF?B,TNF-? IL-1?in The Spinal Dorsal Horn Of Rats With Neuropathic Pain

Objective The analgesic effect of intraperitoneal injection of oxycodone hydrochloride on neuropathic pain and on the expression of phosphor-nuclear factor-kB?p-NF?B?,tumor necrosis factor-??TNF-??and interleukin-1??IL-1??in the spinal dorsal horn were observed to explore the possible mechanism of oxycodone hydrochloride on analgesia of neuropathic pain.Methods 60 specific pathogen free?SPF?rats were randomly divided into three groups of sham operation group,model group and experiment group,with 20 cases in each group.In the model and experiment groups,the rat model of neuropathic pain was constructed by chronic constriction injury?CCI?of the right sciatic nerve.Only the sciatic nerve was exposed and ligation was not performed in the sham operation group.After modeling,the rats in the experiment group were intraperitoneally injected with 15?g/kg oxycodone hydrochloride.In the sham operation and model groups,the rats were injected with equivalent normal saline.In all the groups,the intervention was performed for continued 14 days.The paw withdrawal latency?PWL?of radiant heat stimulation and paw withdrawal threshold?PWT?of mechanical stimulation in each group were measured at 2 days before modeling and at 1,3,7 and 14 days after modeling.Rat spinal cords were collected before modeling and at 1,7,and 14 days after modeling.The mRNA and protein expression of p-NF?B,TNF-?and IL-1?gene were measured by reverse transcriptase polymerase chain reaction?RT-PCR?and Western blot respectively.The protein expression of TNF-?and IL-1?in the spinal dorsal horn of the rats was detected by immunohistochemistry.Results 1)Ethology observation:The rats in all groups were successfully modeled.The rats in the model and experiment groups showed typical spontaneous hyperalgesia signs,including hind limbs reluctant to the ground,slight plantar eversion,gait claudication and frequent dangling of right posterior foot.There were no spontaneous hyperalgesia signs in the rats of sham operation group.2)Pain threshold stimulation experiment:Compared with those at 2d before modeling,there was no significant change in PWL or PWT on the operation side in sham operation group after operation?P>0.05?.PWL and PWT values in model group and experiment group had a trend of decreasing first and increasing then?P<0.05?.PWL and PWT values in the model group and the experiment group were significantly lower than those in the sham operation group at 1,3,7 and 14days after operation?P<0.05?.The above indexes in the model group were significantly lower than those in the experiment group?P<0.05?.3)RT-PCR experiment:The expression quantities of p-NF?B,TNF-?and IL-1?mRNA in the model group and experiment group increased at different levels at 1,7 and 14 days after operation?P<0.05?.There were significant differences in the above indexes in the above two groups compared with the sham operation group?P<0.05?.The expression quantities of the experiment group were significantly lower than those of the model group at 7 and 14days after operation?P<0.05?.4)Western blot experiment:The expression quantities of p-NF?B,TNF-?and IL-1?protein in the experiment group and the model group were significantly increased at the 7^thand 14^thday after operation?P<0.05?.The expression quantities of p-NF?B,TNF-?and IL-1?protein in the experiment group and the model group were significantly higher than those in the sham operation group at7 and 14 d after operation?P<0.05?.The above indexes in the experiment group were significantly lower than those in the model group?P<0.05?.5)Immunohistochemistry experiment:Immunohistochemistry images showed that there were different degrees of staining in spinal cord tissues in the experiment group and the model group at 7 and 14days after operation.The staining scores were significantly higher than those before operation?P<0.05?.At 7 and 14 days after operation,the immunohistochemical staining scores of TNF-?and IL-1?in the model group and the experiment group were significantly higher than those in the sham operation group?P<0.05?.The above scores in the experiment group were significantly lower than those in the model group?P<0.05?.Conclusion The intraperitoneal injection of oxycodone hydrochloride can effectively improve the pain threshold in rats with neuropathic pain.The mechanism might be associated with the decreased expression of p-NF?B,TNF-?and IL-1?mRNA and protein in spinal cord,and with the inhibition of inflammatory response in the body after oxycodone hydrochloride injection.