Antagonistic Effects Of Koumine On Type â…  And Type â…¡ Diabetic Neuropathic Pain In Rats

Diabetic neuropathic pain is an important type of neuropathic pain. The number of people who attacked by this kind of disease is very large. The basis of the treatment of diabetic neuropathic pain is in control of blood glucose. However, So far, it is still a lack of satisfactory clinical analgesic drugs, the treatment satisfaction rate is less than thirty percent or less. The exploration of DNP mechanism, and searching for effective prevention and control of new drugs, as one of the hot research topic at present.Gelsemium elegans Benth, a small genus of the family Loganiaceae. The indole alkaloids are the main effective ingredients in G. Benth. Koumine is the most ingredient and low toxicity effective ingredients in the indole alkaloids of G. Benth. Our large number of previous work showed that koumine has a significant advantages of high-efficiency, resistance to chronic pain. However, what is the effect of koumine for diabetic neuropathic pain? These feature need to be explored.As a result,the paper is in type I and type II diabetic neuropathy pain model, With mechenical withdrawal threshold, sciatic nerve morphology, nerve conduction velocity as observation indexes,further defined the effect of koumine resistance of DNP and its characteristics. In order to put forward the possible effect of koumine on DNP and its theoretical basis,for it may provide a scientific basis for the development and utilization. The main research content is as follows:1. Antagonistic effects of koumine on type I diabetic neuropathic pain rats.In typeⅠdiabetic neuropathy pain(large dose of intraperitoneal injection of STZ) rats model, SD rats were randomly divided into control group, model group, koumine group (7mg/kg,1.4mg/kg,0.28mg/kg,0.056mg/kg), gabapentin100mg/kg group. Since modeling22days subcutaneous injection corresponding drugs,1times a day,for7days,The mechenical withdrawal threshold were tested （on day7、14、21and60min after administration）to know the effect of koumine toward Mechanical hyperalgesia on PDN rats. After the final determination of mechanical pain threshold to determine the sciatic nerve conduction velocity, determination after sciatic nerve morphology analysis, observation effects of koumine on typeIdiabetic neuropathic pain.1.1Continuous subcutaneous injection koumine effects on typeⅠdiabetic neuropathy pain rats blood glucose and body weight.Diabetic rats after modeling showed different degrees of drinking, eating, urinary symptoms and weight loss, color yellow, depression. koumine had no effect on the blood glucose and body weight of diabetic neuropathy pain rats.1.2Koumine can significantly improve typeⅠdiabetic neuropathy pain rats mechanical pain hypersensitivity.It was shown that koumine have significantly effect on mechanical allodynia of DNP rats. Each dose group of koumine(7mg/kg,1.4mg/kg,0.28mg/kg,0.056mg/kg) in rats which takes effect after the treatment, along with the extension of time, the strongest effect appears on day7after the treatment,it remind that koumine have the effect of mechanical hyperalgesia on DNP rats.1.3Koumine can improve nerve conduction velocity of rat sciatic nerve on typeⅠdiabetic neuropathy pain rats.The results showed that subcutaneously give koumine for7days, the koumine group rats(7mg/kg,1.4mg/kg) sciatic nerve conduction velocity compared with model group is on the rise, there are significant differences.It was shown that koumine can improve type Ⅰ diabetic neuropathy pain nerve conduction velocity of rat sciatic nerve.1.4Koumine can improve the changes of sciatic nerve morphology on typeⅠdiabetic neuropathy pain rats.It was showed that at a dose of0.28,1.4and7mg/kg, but not0.056mg/kg koumine alleviated the damage to myelin structure and vacuolar defects and significantly mitigated the lamellar separation Sciatic nerve morphology were tested.It was shown that koumine can improve sciatic nerve morphology on typeⅠdiabetic neuropathy pain rats. 2. Antagonistic effects of koumine on typeⅡdiabetic neuropathic pain ZDF rats.In typeⅡdiabetic neuropathy pain(ZDF rats) rats model, ZDF rats were randomly divided into control group, model group, koumine group (15mg/kg,1.5mg/kg,0.15mg/kg), gabapentin100mg/kg group. Since the rats was born75days intragastric administration corresponding drugs,1times a day,for10days,The mechenical withdrawal threshold were tested（on birth day56、60、63、67、70、74and60min after administration）to know the effect of koumine toward Mechanical hyperalgesia on PDN rats. After the final determination of mechanical pain threshold to determine the sciatic nerve morphology analysis, observation effects of koumine on typeⅡZDF diabetic neuropathic pain.2.1Continuous intragastric administration koumine effects on typeⅡdiabetic neuropathy pain ZDF rats body weight.Diabetic rats after modeling showed different degrees of drinking, eating, urinary symptoms.koumine had no effect on body weight of diabetic neuropathy pain rats.2.2Koumine can significantly improve mechanical pain hypersensitivity caused by diabetes.In order to further clarify the effect on single-dose intragastric infusion of koumine on typeⅡdiabetic neuropathy pain.The mechenical withdrawal threshold were tested （on birth day56、60、63、67、70、74and60min after administration）to know the effect of koumine toward Mechanical hyperalgesia on DNP ZDF rats.It was shown that koumine have significantly effect on mechanical allodynia of DNP rats. Each dose group of koumine(15mg/kg,1.5mg/kg,0.15mg/kg) in rats which takes effect after the treatment, along with the extension of time, the strongest effect appears on day10after the treatment,it remind that koumine have the effect of mechanical hyperalgesia on DNP ZDF rats.2.3Koumine can improve the changes of sciatic nerve morphology on typeⅡdiabetic neuropathy pain ZDF rats.It was showed that koumine is still visible myelin sheaths nerve fibers degeneration, but the degree of myelin lesions compared with model group have different degrees of improvement, basic normal schwann cell structure. It was shown that koumine can improve sciatic nerve morphology on typeⅡdiabetic neuropathy pain ZDF rats.These results suggest that koumine has a therapeutic effect on type Ⅰand type Ⅱ diabetic neuropathy pain.