Role of endogenous melatoninergic system in development of hyperalgesia and tolerance induced by chronic morphine administration in rats
Role of endogenous melatoninergic system in development of hyperalgesia and tolerance induced by chronic morphine administration in rats
复制标题
内源性褪黑素能系统在大鼠慢性吗啡引起的痛觉过敏和耐受性发展中的作用
DOI：
10.1016/j.brainresbull.2017.10.005
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发表时间：
2017-10-01
影响因子：
3.8
通讯作者：
Song, Li
中科院分区：
文献类型：
--
作者：
Fan, Yuchao;Liang, Xiao;Song, Li
吗啡是一种广泛用于各种疼痛的止痛药。然而，其功效受到痛觉过敏和耐受性的发展的阻碍。褪黑激素具有抗伤害性感受作用，并参与吗啡引起的痛敏和耐受，但其机制尚不清楚。本研究建立了吗啡诱导的大鼠痛敏和耐受模型。本实验观察了吗啡诱导的痛敏和耐受大鼠血清褪黑素水平及脊髓背角μ阿片受体（莫尔）、褪黑素受体（MT 1、MT 2）和蛋白激酶C γ（PKC γ）的表达。与对照组（n = 6）相比，吗啡诱导痛敏耐受组（n = 6）大鼠血清褪黑素水平显著降低，脊髓背角MT 1表达减少，而PKC γ表达上调。这些结果将有助于揭示阿片类药物引起痛敏和耐受的机制，并为疼痛治疗探索新的药物。
Morphine is a widely used analgesic for various types of pain. However, its efficacy is impeded by development of hyperalgesia and tolerance. Melatonin has antinociceptive effect and is involved in morphine-induced hyperalgesia and tolerance but the mechanism of its involvement remains to be defined. In this study, we established a rat model of morphine-induced hyperalgesia and tolerance. We determined the serum level of melatonin and expression of mu-opioid receptor (MOR), melatonin receptor (MT1, MT2) and protein kinase C gamma(PKC gamma) in the spinal dorsal horn of the rats with morphine-induced hyperalgesia and tolerance. Comparing with control group (n = 6), the group (n = 6) of rats with morphine-induced hyperalgesia and tolerance exhibited a significant lower serum melatonin level, reduction in expression of the MT1, but up-regulation of the PKC gamma in the spinal dorsal horn. These results may facilitate revealing the mechanism of opioid-induced hyperalgesia and tolerance and exploring new therapeutic remedy for pain management.