尼古丁戒断诱发疼痛敏感性升高的中枢神经机制
钟嘉慧¹, 毕研芝^2,3,*, 孔亚卓^3,4, 陆智杰⁵, 胡理^2,3
1辽宁师范大学脑与认知神经科学研究中心，大连 116029；²中国科学院心理健康重点实验室(中国科学院心理研究所)，北京 100101；³中国科学院大学心理学系，北京 100049；⁴中国科学院行为科学重点实验室(中国科学院心理研究所)，北京 100101；⁵第二军医大学附属东方肝胆外科医院，上海 200433
摘要
尼古丁作为香烟中的主要成瘾物质，它可以通过调节吸烟者体内多种神经递质的释放及其受体的激活，使吸烟者对香烟产生依赖，难以戒断。临床研究发现尼古丁戒断患者的痛阈降低，疼痛敏感性升高。接受手术治疗的尼古丁戒断患者对阿片类镇痛药物需求大大增加，造成了恶心、呕吐、呼吸抑制等副作用，阻碍了患者的身心康复。然而，尼古丁戒断诱发疼痛敏感性升高的神经机制尚不清楚。本文首先综述了尼古丁成瘾及戒断后疼痛敏感性的变化趋势及疼痛刺激类型对此变化趋势的影响，然后系统总结了尼古丁戒断后脑内血清素、去甲肾上腺素、内源性阿片、多巴胺、γ-氨基丁酸等神经递质的释放及其受体激活的变化对疼痛敏感性的影响。最后，本文提出未来研究应关注人类研究，尤其是慢性疼痛患者，使用功能磁共振成像技术可为揭示尼古丁戒断诱发疼痛敏感性升高的人脑神经机制提供帮助。此外，在制定疼痛治疗方案时，应充分考虑到尼古丁戒断方式和戒断时间对疼痛敏感性的影响以及患者性别、慢性疼痛史等个体间差异对戒断后疼痛敏感性的影响。总体来说，本文既能加深我们对于尼古丁戒断后疼痛敏感性变化趋势及其机制的认识，也能为医护人员进行临床疼痛诊断和治疗提供有效的科学理论指导，具有一定的临床应用价值。
关键词： 尼古丁戒断; 疼痛敏感性; 神经递质; 受体; 机制
分类号：Q426

Central neural mechanism of increased pain sensitivity induced by nicotine abstinence
ZHONG Jia-Hui¹, BI Yan-Zhi^2,3,*, KONG Ya-Zhuo^3,4, LU Zhi-Jie⁵, HU Li^2,3
1Research Center of Brain and Cognitive Neuroscience, Liaoning Normal University, Dalian 116029, China；²The Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China；³Department of Psychology, University of Chinese Academy of Sciences, Beijing 100049, China；⁴The Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China；⁵Department of Anesthesiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200433, China
Abstract
Nicotine is the main addictive component in cigarettes that motivates dependence on tobacco use for smokers and makes it difficult to quit through regulating a variety of neurotransmitter release and receptor activations in the brain. Even though nicotine has an analgesic effect, clinical studies demonstrated that nicotine abstinence reduces pain threshold and increases pain sensitivity in smoking individuals. The demand for opioid analgesics in nicotine abstinent patients undergoing surgery has greatly increased, which results in many side effects, such as nausea, vomiting, and respiratory depression, etc. In addition, these side effects would hinder patients’ physical and psychological recovery. Therefore, identifying the neural mechanism of the increase of pain sensitivity induced by nicotine abstinence and deriving a way to cope with the increased demand for postoperative analgesics would have enormous basic and clinical implications. In this review, we first discussed different experimental pain stimuli (e.g., cold, heat, and mechanical pain)-induced pain sensitivity changes after a period of nicotine dependence/abstinence from both animal and human studies. Then, we summarized the effects of the brain neurotransmitter release (e.g., serotonin, norepinephrine, endogenous opioids, dopamine, and γ-aminobutyric acid) and their corresponding receptor activation changes after nicotine abstinence on pain sensitivity. Finally, we discussed the limits in recent studies. We proposed that more attention should be paid to human studies, especially studies among chronic pain patients, and functional magnetic resonance imaging might be a useful tool to reveal the mechanisms of abstinence- induced pain sensitivity changes. Besides, considering the influence of duration of nicotine dependence/abstinence and gender on pain sensitivity, we proposed that the effects of nicotine abstinence and individual differences (e.g., duration of abstinence from smoking, chronic/acute abstinence, and gender) on abstinence-induced pain sensitivity should be fully considered in formulating pain treatment protocols. In summary, this paper could deepen our understanding of nicotine abstinence-induced pain sensitivity changes and its underlying neural mechanism, and could also provide effective scientific theories to guide clinical pain diagnosis and treatment, which has important clinical significance.


Key words: nicotine abstinence; pain sensitivity; neurotransmitter; receptor; mechanism

收稿日期：2020-12-05　　录用日期：2021-03-12
通讯作者：毕研芝　　E-mail: biyz@psych.ac.cn
引用本文：
钟嘉慧, 毕研芝, 孔亚卓, 陆智杰, 胡理. 尼古丁戒断诱发疼痛敏感性升高的中枢神经机制[J]. 生理学报 2021; 73 (6): 953-962.
ZHONG Jia-Hui, BI Yan-Zhi, KONG Ya-Zhuo, LU Zhi-Jie, HU Li. Central neural mechanism of increased pain sensitivity induced by nicotine abstinence. Acta Physiol Sin 2021; 73 (6): 953-962 (in Chinese with English abstract).



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