拉科酰胺对神经病理性痛大鼠背根神经节Nav1.8表达的影响

Effect of lacosamide on expression of Nav1.8 in dorsal root ganglia in a rat model of chronic neuropathic pain

目的 探讨拉科酰胺对神经病理性痛大鼠背根神经节（DRG）Nav1.8表达的影响.方法 SPF级雌性SD大鼠36只,体重120～130 g,采用随机数字表法,将其随机分为3组（n=12）：假手术组（S组）、模型组（M组）、拉科酰胺组（L组）.M组和L组将钢棒插入椎间孔压迫L5DRG制备神经病理性痛模型.于术前2 d、术后2,4、6、7、8、9、10 d（T0-7）时测定机械痛阈.于T4时,S组和L组腹腔注射拉科酰胺20 mg/kg（生理盐水溶解至0.5 ml）,M组注射生理盐水0.5 ml,2次/d,连续4 d.每天末次给药后测定痛阈.于T7时痛阈测定后取术侧L5DRG,采用RT-PCR法和免疫组织化学法测定Nav1.8mRNA和蛋白表达水平.结果 与S组比较,M组和L组T1～7时机械痛阚降低,Nav1.8 mRNA和蛋白表达上调（P〈0.05）;与M组比较,L组T4～7时机械痛阈升高,Nav1.8 mRNA和蛋白表达下调（P〈0.05）.结论 拉科酰胺减轻大鼠慢性神经病理性痛的机制与下调损伤DRG的Nav1.8表达有关.

Objective To investigate the effect of lacosamide on expression of Nav1 .8 in dorsal root ganglia （DRG） in a rat model of chronic neuropathic pain.Methods Thirty-six female specific-pathogen-free （SPF）SD rats were randomly assigned into 3 groups （ n = 12 each）： sham operation group （group S）, model group （group M） and lacosamide group （group L） . Chronic neuropathic pain was produced by insertion of a small stainless steel rod （4.00 mm in length and 0.63 mm in diameter） into the L, intervertebral foramen in the rat, producing a chronic steady compression of the DRG in M and L groups. The mechanical threshold was measured 2 days before operation and on the 2, 4, 6, 7, 8, 9 and 10 days after operation （T0-7 ） . Intraperitoneal lacosamide 20mg/kg （in normal saline 0.5 ml） was injected at T4-7, twice a day in S and L groups. In group M, normal saline 0.5 ml was injected at T4-7 twice a day and the mechanical threshold was measured after the last administration everyday . The L, DRG on the operated side was removed after measurement of pain threshold to detect the expression of Na, 1.8 mRNA and protein by RT-PCR and immuno-histochemistry respectively. Results Compared with group S, the mechanical pain threshold was significantly decreased at T1-7 and the expression of Navl .8 mRNA and protein was up-regulated in M and L groups （ P 〈 0.05） . Compared with group M, the mechanical pain threshold was significantly increased at T4-7 and the expression of Nav 1.8 mRNA and protein was down-regulated in group L （ P 〈 0.05） . Conclusion The mechanism by which lacosamide reduces chronic neuropathic pain is related to the down-regulation of the expression of Nav 1.8 in rat DRG.