摘要
目的探讨脊髓神经元型一氧化氮合酶（nNOS）在大鼠神经病理性痛中的作用。方法健康雄性SD大鼠40只，体重220-280g，采用结扎坐骨神经干的方法建立坐骨神经慢性压迫性损伤（CCI）模型。随机分为4组（n=10），Ⅰ组及Ⅱ组暴露坐骨神经干，分别于术后1d开始鞘内注射选择性nNOS抑制剂7-NI 60μg[溶于20％二甲基亚砜（DMSO）]10μl）、20％DMSO 10ul，1次／d，连续6d；Ⅲ组及Ⅳ组制备CCI模型，分别于术后1d开始鞘内注射7-NI60μg（溶于20％DMSO 10μl）、20％DMSO 10μl，1次／d，连续6d。分别于CCI前1d、CCI后1、3、5、7d时测定大鼠机械痛阈和热痛阈。于CCI后7d，各组分别取5只大鼠，取术侧L4-6背根神经节，分别采用实时定量PCR和Western blot法测定nNOS mRNA及蛋白的表达水平。结果与Ⅰ组和Ⅱ组比较，T1-4时Ⅲ组和Ⅳ组术侧后肢机械痛阈和热痛阈降低（P〈0．05），背根神经节nNOS蛋白及mRNA的表达上调（P〈0．05）；与Ⅲ组比较，T1-4时Ⅳ组机械痛阈和热痛阈降低，背根神经节nNOS蛋白及mRNA的表达上调（P〈0．05）。结论脊髓nNOS参与了大鼠神经病理性痛的形成。
Objective To investigate the role of spinal neuronal nitric oxide synthase （nNOS） in neuropathic pain in rats. Methods Male SD rats weighing 220-280 g were used in this study. The rats were implanted with chronic intrathecal （IT） catheters. Forty rats with normal motor function were randomly divided into 4 groups （ n = 10 each）： group Ⅰ sham operation ＋ 7-nitorindaxole （7-NI） ; group Ⅱ sham operation ＋ DMSO; group Ⅲ CCI ＋ 7-NI and group Ⅳ CCI ＋ DMSO. Neuropathic pain was induced by chronic constrictive injury （ CCI）. Right sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 chromic catgut. In sham operation groups right sciatic nerve was exposed but not ligated. In group Ⅰ and m 7-NI （a selective nNOS inhibitor） 60 μg in 20% DMSO 10 μl was injected IT once a day for 6 consecutive days while in group Ⅱ and Ⅳonly the solvent 20% DMSO 10 μl was injected IT instead of 7-NI. Paw withdrawal threshold （PWT） to mechanical stimulation with von Frey filaments and paw withdrawal latency （PWL） to radiant heat were measured before operation （baseline） and at 1, 3, 5, 7 d after operation. Five animals in each group were killed on the 7th day after operation after last pain threshold measurement. The dorsal root ganglions （DRGs） of the lumbar segment （L4-6 ） were removed for determination of the expression of nNOS mRNA （by RT-PCR） and protein （by Western blot）. Results CCI significantly decreased the mechanical and thermal pain thresholds and increased the expression of nNOS mRNA and protein in the ipsilateral DRGs. IT 7-NI administration significantly suppressed the expression of nNOS in the lumbar DRGs and significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia. Conclusion The spinal nNOS is involved in the formation of neuropathic pain.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2010年第2期170-173,共4页
Chinese Journal of Anesthesiology
基金
国家自然科学基金（30801072）
山东省自然科学基金（Q2007C14）
关键词
神经痛
注射
脊髓
一氧化氮合酶
Neuralgia
Injections, spinal
Nitric oxide synthase
