Effects Of Tetramethylpyrazine On Neuronal Apoptosis In The Superficial Dorsal Horn Of The Rats With Neuropathic Pain

Objective:The aims of this article are to observe the effects of tetramethylpyrazine (TMP) on the neuronal apoptosis in the superficial dorsal horn caused by chronic constrictive injury of sciatic nerve and the expressions of caspase-3and bcl-2which are the two genes closely related with apoptosis, and to explore the therapeutic effects and potential mechanism of tetramethylpyrazine n the neuropathic pain, which may provide theoretical basis for treatment.Methods:Fifty-four male SD rats weighing180-220g were randomly divided into3groups (n=18each):sham operation group (group S), model group (group M) and tetramethylpyrazine group (group T). Neuropathic pain was induced by chronic constriction injury (CCI) in group M and T. The animals were anesthetized with intraperitoneal chloral hydrate300mg/kg. In group S, the right sciatic nerve was exposed but not ligated, and in group M and T, four ligatures were placed on the right sciatic nerve at lmm interval with4-0silk suture. In group T, tetramethylpyrazine100mg/kg was administered intraperitoneally once a day for14consecutive days after operation, while equal volume of normal saline was used to instead of tetramethylpyrazine in group S and M.Mechanical withdrawl threshold (MWT) and thermal withdrawl latency (TWL) was measured at1day before (baseline) and3,7and14day after operation. Six animals in each group were sacrificed after pain threshold measurement on the3rd,7th, and14th days after operation and the lumbar segment L4～6of the spinal cord was removed for determination of bcl-2and caspase-3expression (by immuno-histochemistry) and 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 with1day before operation and group S, MWT and TWL was reduced, the expression of bcl-2and caspase-3and AR was increased in the spinal dorsal horn at3,7and14day after operation in group M and T (P<0.05). MWT and TWL and the expression of bcl-2was increased, the expression of caspase-3and AR was decreased at3,7and14day after operation in group T as compared with group M (P<0.05). Conclusion:Tetramethylpyrazine can attenuate neuropathic pain via inhibiting the neuronal apoptosis in spinal dorsal horn in a rat model of neuropathic pain.