曲马多对神经病理性痛大鼠中脑远位触液神经元5-HT1A受体表达的影响  

Effect of tramadol on expression of 5-HT1A receptor in distal cerebrospinal fluid contacting neurons in mid-brain in a rat model of neuropatlic pain

作　　者：蒋文旭[1] 尹宁[1] 王玲 张励才[3] 

机构地区：[1]南京医科大学附属南京儿童医院麻醉科,210000 [2]南京市浦口医院重症监护室 [3]徐州医学院江苏省麻醉学重点实验室

出　　处：《中华麻醉学杂志》2010年第6期708-711,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（30871307）

摘　　要：目的 探讨曲马多对神经病理性痛大鼠中脑远位触液神经元5-HT1A受体表达的影响.方法 SPF级雄性SD大鼠40只,体重220～280 g,采用坐骨神经慢性压迫法制备大鼠神经病理性痛模型,随机分为5组（n=8）：正常对照组（C组）、生理盐水组（NS组）、曲马多组（T组）、神经病理性痛＋生理盐水组（NP＋NS组）和神经病理性痛＋曲马多组（NP＋T组）.C组不行任何处理;NS组和T组仅暴露坐骨神经,分别腹腔注射生理盐水2 ml/kg或曲马多10 mg/kg;NP＋NS组和NP＋T组制备神经病理性痛模型,模型制备后第7天分别腹腔注射生理盐水2 ml/kg或曲马多10 mg/kg.除C组外,其余4组于腹腔注射曲马多或生理盐水前（T1）和注射后1 h（T2）时测定热痛阈和机械痛阈.于模型制备后第5天,左侧侧脑室注射30%霍乱毒素亚单位B与辣根过氧化物酶复合物（CB-HRP）3μl以标记远位触液神经元,并测定远位触液神经元5-HT1A表达水平.结果 与C组比较,NP＋NS组中脑远位触液神经元5-HT1A受体表达下调（P＜0.05）,其余组差异无统计学意义（P＞0.05）;与NS组和T组比较,NP＋NS组中脑远位触液神经元5-HT1A受体表达下调,热痛阈和机械痛阈降低,NP＋T组热痛阈和机械痛阈降低（P＜0.05）,中脑远位触液神经元5-HT1A受体表达差异无统计学意义（P＞0.05）;与NP＋NS组比较,NP＋T组中脑远位触液神经元5-HT1A受体表达上调,热痛阈和机械痛阈升高（P＜0.05）.结论 曲马多可下调中脑远位触液神经元5-HT1A受体的表达,该作用可能是其减轻大鼠神经病理性痛的机制之一.Objective To investigate the effect of tramadol on the expression of 5-HT1A receptor in the distal＇cerebrospinal fluid contacting neurons （CSF-CNs） in mid-brain in a rat model of neuropathic pain. Methods Forty male SPF SD rats weighing 220-280 g were randomly divided into 5 groups （n = 8 each）： group Ⅰ normal control （group C）; group Ⅱ normal saline （group NS）; group Ⅲ tramodol （group T）; group Ⅳ neuropathic pain ＋ normal saline （group NP＋ NS） and group Ⅴ neuropathic pain ＋ tramadol （group NP ＋ T）. Neuropathic pain was induced by chronic constrictive injury （CCI） in group Ⅳ and Ⅴ . Four silk ligatures were placed on the sciatic nerve at 1 mm intervals. In group Ⅱ （NS） and group Ⅲ （T） the sciatic nerve was exposed but not ligated and NS 2 ml/kg and tramadol 10 mg/kg were injected IP respectively, while in group Ⅳ and Ⅴ NS 2 ml/kg and tramadol 10 mg/kg were injected IP respectively on the 7th day after CCI. Paw withdrawal threshold （PWT） to von Frey filament stimulation and paw withdrawal latency （PWL） to noxious thermal stimuli were measured before （T1） and after IP NS or tramadol injection （T2） in group Ⅱ-Ⅴ. The distal CSF-CNs in the mid-brain was labelled with 30% cholera toxin subunit B and horseradish peroxidase compound （CB-HRP） 3 μl injected in left lateral cerebral ventricle. The expression of 5-HT1A receptors was measured by immuno-histochemistry. Results PWT and PWL were significantly decreased after CCI in group Ⅳ （NP ＋ NS） and tramadol significantly inhibited the mechanical and thermal hyperalgesia in group Ⅴ （NP ＋ T）. There was no significant difference in the number of distal CSF-CNs among the 5 groups. CCI significantly down-regulated the expression of 5-HT1A in distal CSF-CNs in group Ⅳ（NP＋ NS） as compared with group Ⅰ , Ⅱ and Ⅲ and tramadol significantly inhibited the CCI-induced downregulation of 5-HT1A receptor expression. Conclusion Tramadol can ease neuropathic pain

关 键 词：曲马朵 神经元 受体 血清素 5-HT1A 神经痛 

分 类 号：R96[医药卫生—药理学]