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椎管内注射牛肾上腺髓质22肽差异性翻转吗啡耐受作用

江剑平, 陈雅娟, 洪炎国

福建师范大学生命科学学院人体解剖生理教研室,福建省发育和神经生物学重点实验室.福建,福州 350007

摘要

牛肾上腺髓质22肽（bovine adrenal medulla22，BAM22）是脑啡肽原A的一种降解产物，与阿片受体和感觉神经元特异性受体（sensory neuron--specific receptor，SNSR）均有亲合力。该研究的目的是探讨BAM22对吗啡耐受的影响。连续7d对大鼠椎管内注射20#mu#g吗啡形成吗啡耐受后，分为吗啡组、盐水组和BAM22组，d8三组大鼠椎管内分别注射吗啡、生理盐水和BAM22，d9三组大鼠椎管内均注射吗啡后，运用撤足反射、福尔马林实验和免疫组织化学等方法观察吗啡的作用效果。结果显示：在撤足反射实验中，BAM22组的吗啡能延长撤足反射潜伏期最大可能作用的48.5％，并持续约1h：在福尔马林实验中，BAM22组的吗啡能分别缩短福尔马林引起的第一期和第二期疼痛行为变化3.2min和24min，比盐水组分别减少45％和82％（{sl P}<0.05，{sl P}<0.001）；此外，在免疫组织化学实验中，BAM22组的吗啡能显著减少热刺激引起的脊髓背角c--Fos蛋白表达，其Ⅰ--Ⅱ层、Ⅲ--Ⅳ层和Ⅴ--Ⅵ层均减少约80％（{sl P}<0.001）。该研究从整体和细胞水平表明，BAM22能翻转吗啡的耐受，这种作用在持续性疼痛模型中的表现要比急性痛中更为明显，显示BAM22对吗啡耐受的差异性调制；同时也提示感觉神经元特异性受体可能参与吗啡耐受的调制。

关键词： 牛肾上腺髓质22肽; 吗啡耐受; 伤害性感受; 脊髓背角; c-Fos蛋白

Differential reversal effect of intrathecal bovine adrenal medulla peptide 22 on morphine tolerance in rats

Jiang Jianping, Chen Yajuan, Hong Yanguo

Department of Anatomy and Physiology, College of Life Sciences, Fujian Normal University, Key Laboratory of Developmental and Neurological Biology of Fufian Province.Fuzhou 350007,Fujian

Abstract

Bovine adrenal medulla 22 （BAM22）, an endogenous opioid peptide, is one of the cleavage products of proenkephalin A. It potently activates opioid receptors and sensory neuron-specific receptor （SNSR）. The present study was aimed at investigating the effect of BAM22 on morphine tolerance. Intrathecal （i.t.） administration of morphine for 7 d produced-morphine tolerance in rats. Then the rats were divided into three groups in which morphine, saline or BAM22 were administered i.t., respectively, on day 8, and morphine was given to all of the animals on day 9. It was found that morphine administered on day 9 resumed antinociceptive effects in BAM22 group, but not in saline or morphine group. The potency of morphine in BAM22 group was 48.5% of the maximal possible effect （MPE） detected by paw withdrawal test and the antinociception persisted for approximately 1 h. Following the similar treatment, morphine administered on day 9 reduced nocifensive behaviors by 3.2 rain and 24 rain in BAM22 group in the first and second phases, in the formalin test, respectively. The decreases were 45% and 82% of the corresponding values observed in saline group. Furthermore, following the treatment with BAM22 （10 nmol） on day 8 in morphine-tolerance rats, morphine administered on day 9 decreased the expressions of the heat-evoked c-Fos-like immunoreactivity （FLI） protein by approximately 80% in laminae Ⅰ-Ⅱ, Ⅲ-Ⅳ and Ⅴ-Ⅵ in the spinal cord at L4-L5 compared with that in saline or morphine group. The present study provided evidence at behavioral and cellular levels showing that BAM22 resumed antinociception of morphine. The results that the reversal effect of BAM22 on morphine tolerance was more efficient in persistent pain model than in acute pain may indicate that BAM22 differentially modulates morphine tolerance. The present study suggests that SNSR is involved in the modulation of morphine tolerance.

Key words: bovine adrenal medulla 22;Morphine tolerance;nociception;Spinal dorsal horn;c-Fos protein

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引用本文：

江剑平, 陈雅娟, 洪炎国. 椎管内注射牛肾上腺髓质22肽差异性翻转吗啡耐受作用[J]. 生理学报 2006; 58 (6): .

Jiang Jianping, Chen Yajuan, Hong Yanguo. Differential reversal effect of intrathecal bovine adrenal medulla peptide 22 on morphine tolerance in rats. Acta Physiol Sin 2006; 58 (6): (in Chinese with English abstract).