Role Of Activin A Mediated JNK Signaling Pathway In Inflammatory Response To Incisional Pain Myelitis In Rats

Objective: Postoperative pain is a serious clinical problem that endangers human health,and the mechanisms by which it occurs are not well understood and clinical strategies for its treatment are lacking.Activin-A is a key regulator of inflammation and plays a critical role in controlling the cytokine cascade that drives the inflammatory response.This study aims to observe the changes of heat shrinkage foot latency(TWL)and the expression of Activin-A,JNK,and inflammatory factors(IL-1β,TNF-α)at the spinal cord level at the four time points of preoperative and postoperative 2h,6h,and 24 h by constructing a rat plantar incision model,explore the mechanism of Activin-A on the inflammatory mechanism of postoperative acute pain,and find its association with the JNK signaling pathway and key inflammatory factors,in order to provide new ideas for clinical prevention and treatment of postoperative pain.Methods: Forty-eight male SD rats aged 1 month were randomly divided into control group(S group),incision group(IP group),control+follicle inhibition group(SF group),and incision+follicle inhibition group(IF group).Rats in the SF and IF groups were injected intraperitoneally with follistatin 30 minutes before surgery,both 5 ug/kg.The rats in each group were detected at the following four time points: preoperative(T0),postoperative 2 h(T2),6 h(T6)and 24 h(T24).The thermal shrinkage foot latency(TWL)test was performed on each group of rats at each time point.The changes of spinal cord Activin-A,IL-1β and TNF-α protein content at each time point were detected by ELISA.The expression of Activin-A and JNK at each time point was determined by q PCR,and the results were statistically analyzed.RESULTS: Behavioral test results: There was no significant difference between the preoperative TWL values of the four groups(P>0.05);compared with the preoperative TWL values of the IP and IF groups,the postoperative TWL values decreased at all time points(P<0.05);compared with the S group,the postoperative TWL values of the IP and IF groups decreased significantly at three time points(P<0.05),while the difference between the TWL values of the SF group rats was not statistically significant(P>0.05).Compared to the IP group,TWL values in the IF group increased at three postoperative time points(P<0.05);ELISA results: The differences in the expression of Activin-A,IL-1β and TNF-αwere not statistically significant in the four groups before surgery(P>0.05);compared with the S group,the expression of Activin-A,IL-1β and TNF-α increased in the spinal cord of rats in the IP and IF groups at three time points after surgery(P<0.05),while the above indexes decreased in the SF group(P > 0.05).Compared with the IP group,the expression of Activin-A,IL-1β and TNF-α decreased in the IF group at three postoperative time points(P<0.05);the expression of Activin-A,IL-1β and TNF-α increased in the spinal cord of rats in the IP group at all postoperative time points compared with that before surgery(P<0.05);the expression of IL-1β and TNF-α in the spinal cord of rats in the IF group increased at all postoperative time points compared with that before surgery(P < 0.05);q PCR results: The differences in preoperative Activin-A and JNK expression in the four groups were not statistically significant(P>0.05);compared with the S group,Activin-A and JNK expression increased in the IP and IF groups at three postoperative time points(P < 0.05),while the differences in these indices were not statistically significant in the SF group(P>0.05);compared with the IP group,Activin-A and JNK expression decreased in the spinal cord of the IF group at three postoperative time points(P<0.05);the m RNA expression of Activin-A and JNK in the spinal cord increased significantly in the IP group at all postoperative time points compared with that in the preoperative group(P < 0.05);the expression of Activin-A in the spinal cord was higher in the IF group than in the preoperative group at T2,T6 and T24(P<0.05),and the expression of JNK in the spinal cord at T6 and T24(P<0.05).Conclusions: 1.Activin A participates in the inflammatory response mechanism of rat plantar acute pain by regulating JNK signaling pathway;2.Follicle inhibitor,as an inhibitor of activin A,can reduce the expression of activin A,partially inhibit the activation of JNK signaling pathway,and reduce the release of pro-inflammatory cytokines(IL-1β and TNF-α),thus exerting the effect of relieving acute postoperative pain The effect is to relieve acute postoperative pain.