连续小剂量吗啡腹腔注射对CCI大鼠抗伤害效应的实验研究  

Effect of Low Dose Morphine Continually Administered Intraperitoneally on Antinociception in CCI Rats

作　　者：万丽[1] 罗爱林[1] 田玉科[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院麻醉学教研室,武汉430030

出　　处：《华中科技大学学报（医学版）》2005年第2期232-235,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省自然科学基金资助项目 (No. 2002AA301D09)

摘　　要：目的观察坐骨神经慢性收缩损伤(CCI)后小剂量吗啡连续腹腔注射对大鼠痛敏的影响,以及脊髓背角c-fos基因及TrkA受体表达,探讨吗啡耐受的可能机制.方法选择雌性SD大鼠40只,随机分为4组,A组:假手术组,B组:CCI组,C组:CCI+生理盐水组,D组:CCI+吗啡组[5 mg/(kg·d)],分别于术前2 d,术后7、14 d进行热痛阈测试,免疫组织化学方法检测术后7、14 d c-fos基因及TrkA受体的表达.结果 A组术后术侧热痛阈轻度下降,与术前相比差异无显著性意义.B、C、D组术后术侧呈现不同程度热痛阈下降,以术后14 d为著,B、C组与A组相比,差异均有极显著性意义(均P<0.01),D组与A组相比,差异有显著性意义(P<0.05).CCI术后14 d脊髓c-fos基因、TrkA受体的表达较术后7 d明显增加,c-fos基因的表达主要集中于脊髓背角表层Ⅰ～Ⅱ、Ⅲ～Ⅳ层的中间内侧部,TrkA受体分布于Ⅱ～Ⅴ层.c-fos基因、TrkA受体的表达在B、C、D 3组与A组相比,差异具有显著性意义(P<0.05);D组与B组相比,差异无显著性意义(P>0.05).结论小剂量吗啡连续腹腔注射不能有效抑制坐骨神经损伤后热痛觉过敏及脊髓背角c-fos基因、TrkA受体的表达,可能与长时间使用吗啡导致脊髓背角神经元兴奋性进一步升高,发生中枢可塑性改变,以及脊髓背角神经元μ-阿片受体脱敏感有关.Objective To explore the underlying mechanisms of morphine tolerance in spinal cord by studying the effect of low dose morphine continually administered intraperitoneally after chronic stricture injury (CCI) on the hyperalgesia and the expression of c-fos and TrkA receptor in spinal dorsal horn in rats. Methods Forty female Sprague-Dawley rats were randomly divided into 4 groups: A,sham-operation group; B,CCI group; C: CCI+saline group and D,CCI+morphine group. Thermal pain threshold was assessed on the second day before operation and on the 7th,14th day postoperatively in each group. Immunohistochemistry was performed to detect the expression of the c-fos gene and TrkA receptor.Results The radiant thermal pain threshold was slightly decreased in the ipsilateral hindpaw after operation in group A,but there was no significant difference as compared to the pre-operative value (P>0.05). The radiant thermal pain threshold was decreased to varying degrees in groups B,C and D,especially on the postoperative day 14. There was very significant difference between groups B or C and group A (P<0.01),but significant difference between group D and A (P<0.05). The expression of c-fos and TrkA receptor was significantly increased on 14th day as compared with that on 7th day postoperatively. c-fos was mainly expressed in the dorsomedian in superficial laminae Ⅰ-Ⅱ and Ⅲ-Ⅳ in spinal dorsal horn,while the TrkA receptor in laminae Ⅱ-Ⅴ. There was significant difference in the expression of c-fos and TrkA receptor between groups B,C,D and group A,respectively (P<0.05). Conclusion Low dose morphine (5 mg/kg) continually administered intraperitonealy could not effectively reduce the hyperalgesia in radiant thermal stimulus and the expression of c-fos and TrkA receptor in spinal cord after CCI of the sciatic nerve in rats,which may be related to the dissensitization of the μ-opioid receptor after long-term use of morphine and the plasticity changes of the neurons in spinal dorsal horn.

关 键 词：慢性收缩损伤 痛觉过敏 吗啡 脊髓背角 c—fos基因 TRKA受体 

分 类 号：R971.2[医药卫生—药品]