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内源性褪黑素系统在慢性吗啡给药诱导的痛觉过敏和耐受发展中的作用。

Role of endogenous melatoninergic system in development of hyperalgesia and tolerance induced by chronic morphine administration in rats.

机构信息

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

Department of Pain Management, West China Hospital, Sichuan University, #37, Guo Xue Xiang, Chengdu 610041, Sichuan Province, China.

出版信息

Brain Res Bull. 2017 Oct;135:105-112. doi: 10.1016/j.brainresbull.2017.10.005. Epub 2017 Oct 6.

DOI:10.1016/j.brainresbull.2017.10.005
PMID:28988976
Abstract

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 μ-opioid receptor (MOR), melatonin receptor (MT1, MT2) and protein kinase C γ(PKCγ) 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 PKCγ 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.

摘要

吗啡是一种广泛用于各种类型疼痛的镇痛剂。然而,其疗效受到痛觉过敏和耐受的发展的阻碍。褪黑素具有镇痛作用,并且参与吗啡引起的痛觉过敏和耐受,但参与的机制仍有待确定。在这项研究中,我们建立了吗啡诱导的痛觉过敏和耐受的大鼠模型。我们测定了吗啡诱导的痛觉过敏和耐受大鼠血清褪黑素水平以及脊髓背角中μ-阿片受体(MOR)、褪黑素受体(MT1、MT2)和蛋白激酶 C γ(PKCγ)的表达。与对照组(n=6)相比,吗啡诱导的痛觉过敏和耐受大鼠组(n=6)血清褪黑素水平显著降低,脊髓背角 MT1 表达减少,而 PKCγ 表达上调。这些结果可能有助于揭示阿片类药物引起的痛觉过敏和耐受的机制,并探索疼痛管理的新治疗方法。

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