加巴喷丁对神经病理性痛大鼠背根神经节Cav3．2通道的影响

Effect of gabapentin on Cav3.2 channels in dorsal root ganglia of rats with neuropathic pain

目的评价加巴喷丁对神经病理性痛大鼠背根神经节Cav3.2通道的影响。方法雄性SD大鼠30只，6～7周龄，体重225～275 g，采用随机数字表法分为3组（n＝10）：假手术组（S组）、神经病理性痛组（NP组）和加巴喷丁组（G组）。NP组和G组采用坐骨神经慢性缩窄损伤法制备大鼠神经病理痛模型。术后第7天，G组腹腔注射加巴喷丁100 mg/kg，溶于1 ml生理盐水中，S组和NP组腹腔注射等容量生理盐水，2次/d，连续7 d。分别于术前3 d和术后3、7、14 d时测定机械缩足反应阈（MWT）和热缩足潜伏期（TWL）。于术后14 d痛阈测定结束后分别处死4只大鼠，取术侧L4-6背根神经节，采用RT-PCR法测定Cav3.2 mRNA的表达水平，采用Western blot法测定Cav3.2的表达水平。结果与S组比较，NP组术后3、7和14 d时MWT下降，TWL缩短，背根神经节Cav3.2及其mRNA表达上调，G组术后3和7 d时MWT下降，TWL缩短（P〈0.05），背根神经节Cav3.2及其mRNA表达差异无统计学意义（P〉0.05）；与NP组比较，G组术后14 d时MWT升高，TWL延长，背根神经节Cav3.2及其mRNA表达下调（P〈0.05）。结论加巴喷丁减轻大鼠神经病理性痛的机制可能与抑制背根神经节Cav3.2通道的功能有关。

ObjectiveTo evaluate the effect of gabapentin on Cav3.2 channels in the dorsal root ganglia （DRG） of rats with neuropathic pain.MethodsThirty male Sprague-Dawley rats, aged 6-7 weeks, weighing 225-275 g, were divided into 3 groups （n=10 each） using a random number table： sham operation group （S group）, neuropathic pain group （NP group） and gabapentin group （G group）. In NP and G groups, neuropathic pain was induced by chronic constriction injury to the left sciatic nerve.Starting from 7th day after operation, gabapentin 100 mg/kg in 1 ml of normal saline was injected intraperitoneally twice a day for 7 consecutive days in group G, and the equal volume of normal saline was given twice a day for 7 consecutive days in S and NP groups.The mechanical paw withdrawal threshold （MWT） and thermal paw withdrawal latency （TWL） were measured on day 3 before operation and on postoperative days 3, 7 and 14.After the last measurement of pain thresholds on the postoperative day 14, 4 rats were sacrificed for determination of Cav3.2 mRNA expression （by real-time polymerase chain reaction） and Cav3.2 protein expression （by Western blot） in the DRG.ResultsCompared with S group, the MWT was significantly decreased, and TWL was significantly shortened on postoperative days 3, 7 and 14, and the expression of Cav3.2 protein and mRNA in the DRG was significantly up-regulated in group NP, and the MWT was significantly decreased, and TWL was significantly shortened on postoperative days 3 and 7 （P〈0.05）, and no significant change was found in the expression of Cav3.2 protein and mRNA in the DRG in group G （P〉0.05）. Compared with NP group, the MWT was significantly increased, and TWL was significantly prolonged on the postoperative day 14, and the expression of Cav3.2 protein and mRNA in the DRG was significantly down-regulated in group G （P〈0.05）.ConclusionThe mechanism by which gabapentin attenuates neuropathic pain may be related to inhibition of the function of Cav3.2 channels in the DRG of rats.