Analgesic Effect Of Corydalis Decumbens In Mouse Model Of Neuropathic Pain And Its Mechanism

Objective : postherpetic neuralgia(PHN)model were established by intraperitoneal injection of resiniferatoxin(RTX),and to investigate the analgesic effect of injection of Corydalis Decumbens(ICD)on the neuropathic pain and its mechanism,to discuss the potential value of ICD in the treatment of NeP.Methods:48 healthy Kunming mice,male,18~22 g,were randomly divided into three groups: control,PHN and CD,and 16 mice in each group.The PHN model was established by intraperitoneal injection of RTX in group PHN and group CD,and the group control was injected with the same volume of normal saline.After successful modeling,group CD was treated with 120 ug/kg ICD,and the group PHN was received with the same volume of normal saline for 2weeks.The paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL)were assessed on the 1st day(T0)before RTX injection and the 1st(T1),3rd(T2),5th(T3)and 7th day(T4)after RTX operation and the1st(T5),3rd(T6),5th(T7),7th(T8)and 14 th day(T9)after CD injection treatment.The mice were sacrificed and lumbar spinal tissues were sampled before treatment and after last test of pain threshold,the expression of Iba1 and GFAP in the spinal cord was detected by immunofluorescence staining,andphosphorylation of p38 mitogen? activated protein kinase(p-p38MAPK)and c-Jun N-terminal kinase(p-JNK)were detected by immunofluorescence staining and Western blot,ELISA assay was used to detect the concentrations ofβ-endorphin(β-EP)and substance P(SP)in the homogenate of L4-L6 spinal cord.Result:1.PWMT: after intraperitoneal injection of RTX,compared with T0,PWMT in group PHN and group CD was decreased(P<0.05).After ICD treatment,PWMT in group CD was significantly increased compared with T4,but it was still lower than that in T0(P<0.05).2.PWTL: when PHN model was established successfully,compared with T0,PWTL in group PHN and group CD was significantly increased at T4(P<0.05).After ICD treatment,PWTL in group CD was significantly decreased compared with that in T4,but it was still higher than that inT0.3.Immunofluorescence: the expression of Iba1,GFAP,p-p38 MAPK and p-JNK in group PHN and group CD was significantly higher than group C at T4(P<0.05),but there was no significant difference between group PHN and CD group(P>0.05).At T9,the expression of Iba1,GFAP,phospho-p38 MAPK and phospho-JNK in group CD significantly lower than in group PHN,but still higher than group control(P<0.05).4.WB: after injection of RTX,the expression level of p-p38 MAPK and p-JNK in group PHN and group CD was increased,compared with group control(P<0.05),but there was no significant difference between group PHN and group CD(P>0.05);At T9,the phosphorylation level of p38 MAPK and JNK in group CD was significantly lower than in group PHN(P<0.05).5.ELISA: at T4,the concentration of β-endorphin(β-EP)and substance P(SP)of spinal cord in group PHN and group CD significantly higher than group control(P<0.05),there was no significant differences between the group PHN and group CD(P>0.05);at T9,compared with group PHN,expression of β-EP was increased while SP was decreased in group CD(P<0.05).Conclusion:1.Systemic treatment with RTX generates long-lasting paradoxical changes in thermal and mechanical sensitivities,can replicate the unique clinical symptoms of patients with PHN;2.The activation of microglial and astrocytes in the spinal cord was induced by intraperitoneal injection of RTX,and the expression of p-p38 MAPK and p-JNK increased,the concentrations of β-EP and SP was raised.3.ICD significantly ameliorate the hyperalgesia of PHN model mice,attenuated mechanical hypersensitivity and improved thermal sensitivity induced by RTX,The mechanism may be associated with the reduction of the activation of glial cells and the phosphorylation of the MAPK pathway.