Role of C-Jun N-terminal kinase signal transduction pathway in spinal neurotoxicity induced by lidocaine in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of C-Jun N-terminal kinase (JNK) signal transduction pathway in spinal neurotoxicity induced by lidocaine in rats.Methods Seventy-two adult male Sprague-Dawley rats,weighing 220-260 g,were randomly divided into 6 groups (n =12 each)control group (group Ⅰ),sham operation group (group Ⅱ),JNK inhibitor group (group Ⅲ),dimethyl sulfoxide (DMSO) group (group Ⅳ),lidocaine group (group Ⅴ),and JNK inhibitor and lidocaine group (group Ⅵ).Group Ⅰ received no treatment.Intrathecal catheter was placed in the subarachnoid space in group Ⅱ.SP600125 25 μg and DMSO 20 μl were injected intrathecally in Ⅲ and Ⅳ groups,respectively.In group Ⅴ,10％ lidocaine 20 μl was intrathecally injected.SP600125 25 μg was injected intrathecally and 30 min later 10％ lidocaine 20 μl was injected intrathecally in group Ⅵ.Paw withdrawal threshold to yon Frey filament stimulation (PWT) and paw withdrawal latency to nociceptive thermal stimulation (PWL) were measured before intrathecal catheter was implanted (T0),before intrathecal administration (T1) and at 4,8 and 12 h and on 1,2,3,4,5 and 6 days after intrathecal administration (T2-10).At 24 h after intrathecal administration,4 rats were randomly chosen from each group and sacrificed.Their lumbar enlargements were removed for determination of phosphorylated JNK (p-JNK) expression (using Western blot) and neuronal apoptosis (by TUNEL).The apoptotic index was calculated.Results Compared with group Ⅰ,no significant difference was found in MWT and TWL in Ⅱ,Ⅲ groups and expression of p-JNK in Ⅱ and Ⅳ groups (P ＞ 0.05),MWT at T2-4,6-8 and TWL at T2-4,7 in group Ⅴ and MWT at T2-6 and TWL at T2-5 in group Ⅵ were significantly increased,the expression of p-JNK was down-regulated and the apoptotic index was decreased in group Ⅲ (P ＜ 0.05),and the expression of p-JNK was up-regulated and the apoptotic index was increased in Ⅴ and Ⅵ groups (P ＜ 0.05).Compared with group Ⅴ,MWT and TWL were significantly decreased,the expression of pJNK was down-regulated and the apoptotic index was decreased in group Ⅵ (P ＜ 0.05).Conclusion Activation of JNK signal transduction pathway is involved in spinal neurotoxicity induced by lidocaine in rats possibly through promoting neuronal apoptosis in the spinal cord.