Effects of sinomenine on neuronal apoptosis in spinal dorsal horns in a rat model of neuropathic pain

Objective To evaluate the effects of sinomenine on neuronal apoptosis in the spinal dorsal horns in a rat model of neuropathic pain (NP).Methods One hundred and eight male Wistar rats,weighing 180-220 g,were randomly divided into 3 groups with 36 animals in each group:sham operation group (group S),NP group and sinomenine group (group SIN).The animals were anesthetized with intraperitoneal chloral hydrate.In groups NP and SIN,NP was induced by chronic constrictive injury.The sciatic nerve was exposed and four ligatures were placed on the right sciatic nerve at 1 mm intervals with 4-0 chromic catgut.In group S,the right sciatic nerves were exposed,but not ligated.In group SIN,sinomenine 40 mg/kg was injected intraperitoneally once a day starting from the end of operation until one day before the rats were sacrificed.In groups NP and S,the rats received the equal volume of normal saline instead of sinomenine.Twelve animals in each group were randomly chosen at 1 day before operation (T0) and 3,7 and 14 days after operation (T1-33) to measure mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL).The rats in each group were sacrificed at T1-3 after measurement of pain threshold and the lumbar segments (L4-6) of the spinal cord were removed for determination of caspase-3 mRNA and p38MAPK mRNA expression (by real-time fluorescent quantitative PCR) and cell apoptosis (by TUNEL) in the spinal dorsal horn.Apoptosis rate (AR =the number of apoptotic cells/the total number of cells examined) was calculated.Results Compared with group S,MWT and TWL were significantly decreased,the expression of caspase-3 mRNA and p38MAPK mRNA was up-regulated,and AR was increased at T1-3 in NP and SIN groups (P ＜ 0.05).Compared with group NP,MWT and TWL were significantly increased,the expression of caspase-3 mRNA and p38MAPK mRNA was down-regulated,and AR was decreased at T1-3 in group SIN (P ＜ 0.05).MWT and TWL were significantly lower,and the expression of caspase-3 mRNA and p38MAPK mRNA and AR were higher at T2,3 than at T1 in groups NP and SIN (P ＜ 0.05).Conclusion Sinomenine can attenuate NP through inhibiting the expression of p38MAPK signal transduction pathway and reducing neuronal apoptosis in the spinal dorsal horn of rats. Key words: Sinomenine;  Neuralgia;  Apoptosis;  Spinal cord