Effects Of Sinomemine On Neuronal Apoptosis In Spinal Dorsal Horn In A Rat Model Of Neuropathic Pain

Objective To evaluate the effects of sinomenine on the neuronal apoptosis in the spinal dorsal horn in a rat model of neuropathic pain. By means of determination of caspase-3 mRNA and p38MAPK mRNA expression,to explore the therapeutic effects and potential mechanism of sinomenine in the neuropathic pain.Methods One hundred and eight male Wistar rats whose weight is between 180-220g and age is 6-8 w were randomly distributed into group sham operation (group S), group the chronic constrictive injury (group NP) and group sinomenine (group SIN),36 rats in each group. In groups NP and SIN, chronic sciatic nerve constriction injury model was adopted to set up model of neuropathic pain, while in group S, the right sciatic nerves were only exposed well, but not ligated. In group SIN, sinomenine 40 mg·kg-1·d-1 was immediately injected intraperitoneally starting from the end of surgery until one day before the rats were condemned to death,14 consecutive days. In groups NP and S, the rats received the equal volume of normal saline in the same way. Twelve animals in each group were randomly chosen at lday before operation (To)and 3,7 and 14 days after operation (T1.3)to measure mechanical paw withdrawal threshold (MWT)and thermal paw withdrawal latency (TWL). At the same time, twelve rats in each group were condemned to death at T1-3 after measurement of pain threshold. Taking out the lumbar segment(L4-6) of the fresh spinal cord, which were prepared for detection of apoptosis in the spinal dorsal horn (by TUNEL) and the expression of caspase-3 mRNA and p38MAPK mRNA (by Real-time qPCR).Results Compared with group S, TWL and MWT were obviously reduced, while AR was significantly increased,the expression of p38MAPK mRNA and caspase-3 mRNA was markedly up-regulated at T1.3 in groups NP and SIN (P<0.05). Compared with group NP, TWL and MWT were increased, AR was decreased, the expression of p38MAPK mRNA and caspase-3 mRNA was down-regulated at T1-3 in group SIN (P<0.05). Compared with T1, TWL and MWT were obviously reduced, AR was significantly increased, the expression of p38MAPK mRNA and caspase-3 mRNA was markedly up-regulated at T2,3 in groups NP and SIN (P<0.05).Conclusion Intraperitoneal injection of sinomenine can attenuate neuropathic pain, potential mechanism is through inhibition of p38MAPK signaling pathway, thereby reducting neuronal apoptosis in spinal dorsal horn.