Effects of modified Xuanfuhua Decoction on pain behavior and p38MAPK signaling pathway-mediated spinal cord neuroinflammation in rats with sciatic nerve injury
Objective To observe the effects of modified Xuanfuhua Decoction on pain behaviour and spinal cord neuroinflammation mediated by phosphorylated mitogen-activated protein kinase p38(p38MAPK)signaling pathway in rats with sciatic nerve injury;To analyse the mechanism of its effects.Methods Totally 108 SD rats were randomly divided into sham-operation group,model group,pregabalin group,decoction low-,medium-and high-dosage groups,with 18 rats in each group.The CCI model was established by ligation of sciatic nerve in other groups except sham-operation group.On the postoperative day,the decoction low-,medium-,high-dosage groups were gavaged with 2.5,5.0 and 10.0 g/kg of modified Xuanfuhua Decoction concentrate,respectively.The pregabalin group was gavaged with 15 mg/kg of pregabalin.The sham-operation group and the model group were gavaged with equal amounts of saline once/d for 15 days.Pain behavioural assays were performed before,on the 3rd,7th,11th and 15th day of administration respectively.The levels of interleukin(IL)-1β,tumour necrosis factor-α(TNF-α),IL-10 were detected by ELISA method.The expressions of Toll-like receptor 4(TLR4),nuclear factor-κB p65(NF-κB p65)were detected by immunohistochemistry staining.The phosphorylated p38MAPK(p-p38MAPK)were measured in the spinal cord by Western blot.Results Compared with the model group,the scores of spontaneous pain in decoction high-dosage group decreased(P＜0.05),the thermal foot shrinkage latency(TWL)was prolonged(P＜0.05),and the mechanical foot shrinkage reflex threshold(MWT)increased(P＜0.05);the levels of IL-1β and TNF-α in spinal cord tissue of decoction low-,medium-and high-dosage groups decreased(P＜0.05),the level of IL-10 increased(P＜0.05),the average gray values of TLR4 and NF-κB p65 in spinal cord decreased(P＜0.05),and the expression of P-P38MAPK protein decreased(P＜0.05).Conclusion Modified Xuanfuhua Decoction can effectively improve neurogenic pain in CCI rats,and the mechanism may be related to inhibition of p38MAPK-TLR4 signaling pathway activation-mediated spinal cord neuroinflammation.
PainNeuroinflammatory diseasesModified Xuanfuhua DecoctionPain behaviourp38 Mitogen-activated protein kinasesRats
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