Reversal Effect Of Koumine On Neuropathic Pain

Neuropathic pain is defined as pain "initiated or caused by a primary lesion or dysfunction in the nervours system", which is characterized by spontaneous pain, allodynia, hyperalgesia. It is complicated in terms of its diagnosis and management and it is one of the great challenges in medical treatment. Neuropathic pain with complicated mechanisms is severe and the treatment of neuropathic pain is very difficult. Therefore, it became one of the new drugs exploiture's hotspots more and more.Gelsemium elegans Benth. (G. Benth.) which is indigenous in China, belongs to the genus Gelsemium of Loganiaceae. G. Benth. is abundant in Fujian, Guangdong and Guangxi provinces and so on. The resource of G. Benth. is affluent in Fuzhou. The locals there for a long time used its original plant to cure kinds of pain, especially neuropathic and cancer pain. The indole alkaloids are the main effective ingredients in G. Benth. The clinical and basic researches indicated that, the total alkaloid of G. Benth. have distinct abirritation; its mechanism might be quite different to opioid analgesics and asprin; with the high efficiency which is next to morphine, it brings no drug resistance and addiction as side effects; but, despite of no cumulated toxicity, the therapeutic dosage was close to the toxic dosage which handicapped the application. There were no reports about antalgic activities and cure indexes of any monomeric alkaloids of G. Benth.It must be researched further more. High-speed Countercurrent Chromatography had used for the isolation and purification of koumine. Then,the effects of koumine were explored on CCI (chronic constriction injury) rats and SNL (spinal nerve ligation) rats. To investigate the effect of koumine on neuropathic pain. The study is helpful for appling pre-clinical pharmaceutic data. This research contains two sections as follows:1,The effect of koumine on neuropathic pain caused by chronic constriction injury.The paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT) of left and right was tested respectively, represented as L and R, the data is evaluated by R(injured). The testing were repeated on preoperative day0, postoperative day 3, day5, day7, day9, day10, day11, day13. Each rat received an s.c injection of the appropriate randomly assigned treatment from day3 to day 9, seven successive days, twice a day. The research indicated that koumine produced a dose-dependent improvement in thermal hyperalgesia and mechanical hyperalgesia. High-dose group began to cause a significant improvement when comparing with CCI group after the treatment of two days. The effect was long lasting until 42 hours after treatment withdrawl. On day 9 postopratively, the ED50 of koumine is 0.86 mg/kg(PWL) and 1.13mg/kg(MWT). Low-dose group began to cause a significant improvement when comparing with CCI group after the treatment of four days. The effect was long lasting until 36 hours in PWL and 18 hours in MWT after treatment withdrawl.2,The effect of koumine on neuropathic pain caused by spinal nerve ligation.The paw withdrawal latency (PWL) and mechanical withdrawal threshold (MWT) of left and right was tested respectively, represented as L and R, the data is evaluated by R(injured). The testing were repeated on preoperative day0, postoperative day 3, day5, day7, day9, day10, day11, day13. Each rat received an s.c injection of the appropriate randomly assigned treatment from day3 to day 9, seven successive days, twice a day. The research indicated that koumine produced a dose-dependent improvement in thermal hyperalgesia and mechanical hyperalgesia. High-dose group began to cause a significant improvement when comparing with SNL group after the treatment of two days. The effect was long lasting until 42 hours after treatment withdrawl. On day 9 postopratively, the ED50 of koumine is 0.79 mg/kg(PWL) and 1.58 mg/kg(MWT). Low-dose group began to cause a significant improvement when comparing with CCI group after the treatment of four days. The effect was long lasting until 36 hours in PWL and 18 hours in MWT after treatment withdrawl.It's the first time to report that koumine had the remarkable analgesic effects on neuropathic pain. They got high safety because their effective dosages were far away from their LD50. The high-effective and low-toxic koumine might be filtrated to become new-type analgesic drugs by more researches in the future.