降钙素基因相关肽在慢性吗啡耐受及相关痛觉过敏中的作用

Function of calcitonin gene-related peptides in chronic morphine tolerance and hyperalgesia

疼痛是晚期恶性肿瘤患者的常见症状,是影响患者生存质量的主要因素,阿片类药物吗啡是治疗急慢性疼痛的常用药物,但长时间应用会导致吗啡耐受及其相关痛觉过敏现象的发生,制约其临床应用。本文总结分析近年相关文献,从伤害性感受角度探讨慢性吗啡耐受及其相关痛觉过敏的形成原因,重点阐述降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在其中的作用,从CGRP的分子生物学特征与分布、长期吗啡应用与CGRP的关系、CGRP与痛觉过敏等方面详细分析了慢性吗啡给药所致的神经系统可塑性变化与CGRP表达上调之间的关系,并对CGRP表达上调对机体伤害性感受系统的影响进行分析,阐述了CGRP表达上调与痛觉过敏形成之间的关系。从机制上论述了CGRP表达上调所致的伤害性感受增强对吗啡耐受及其相关痛觉过敏的促进作用,为治疗吗啡耐受和进一步研究吗啡耐受机理提供了一个靶点和思路。

Pain is a common symptom in patients with terminal cancer and is the main factor that affects their quality of life. Morphine is commonly used for the treatment of acute and chronic pain, but the long-time application of morphine results in morphine tolerance and hyperalgesia, which restrict the clinical applications of the anesthetic. In this review, pertinent studies on morphine over recent years were summarized and analyzed, and the mechanism of morphine tolerance and hyperalgesia were discussed, specifically on the function of calcitonin gene-related peptide （CGRP） in clinical practice. The authors analyzed the relationship between the plastic changes in the nervous system and chronic morphine application in terms of CGRP up-regulation based on its molecular biology charac- teristics and distribution, the relationship between CGRP and chronic application of morphine, and between CGRP and hyperalgesia. The effect of CGRP up-regulation on the nociceptive system and the relationship between CGRP up-regulation and the formation of hy- peralgesia were also analyzed. We discussed the sensitized effect of CGRP up-regulation on the nociceptive system, which promotes morphine tolerance and hyperalgesia. This study provides a framework for treating morphine tolerance and can be used as a guide for further research on the topic.