＊国家自然科学基金（30470565）和福建省教育厅（JB04230）资助项目
鞘内注射BAM22差异性翻转吗啡耐受作用的研究
江剑平，陈雅娟，洪炎国*
摘 要：牛肾上腺髓质22肽(bovine
adrenal medulla 22, BAM22)是脑啡肽原A的一种降解产物，它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。本研究的目的是探讨BAM22对吗啡耐受的作用。连续7天鞘内注射吗啡形成吗啡耐受，经第8天BAM22作用后，第9天鞘内注射吗啡能延长撤足反射潜伏期最大可能作用(maximal possible effect, MPE)的48.5 %，并持续约1 h。同样的处理后，第9天鞘内给予吗啡能分别缩短福尔马林试验第一期和第二期疼痛行为变化3.2 min和24 min，比盐水组分别减少45 %和82 %；此外，先期给予BAM22，能使第9天鞘内注射吗啡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层减少均约为80 %。本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(BAM22)；吗啡耐受；伤害性感受；脊髓背角；c-Fos蛋白
Differential reversal effect of intrathecal BAM22
on morphine tolerance in
rats
Department of Anatomy and Physiology,
Key Laboratory of Developmental and Neurological
Biology of
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 on days 1-7 produced morphine tolerance. However, after BAM22 (10 nmol, i.t.), but not saline, was administered
on day 8, i.t. administration of morphine on day 9 resumed
antinociception with potency of 48.5
% maximal possible effect
(MPE), and this effect persisted for approximately 1 h. Following the similar treatment, morphine
administered on day 9 reduced nocifensive behaviors by
3.2 min and 24 min in the first and second phases, in the formalin test, respectively.
In comparison with saline group, 45 and 82 % of decreases were observed.
Furthermore, following the treatment with BAM22 (10 nmol)
on day
Key words: bovine adrenal medulla 22 (BAM22);
morphine tolerance; nociception; spinal
dorsal horn; c-Fos protein