Nicotine dependence produces hyperalgesia: role of corticotropin-releasing factor-1 receptors (CRF1Rs) in the central amygdala (CeA).
Nicotine dependence produces hyperalgesia: role of corticotropin-releasing factor-1 receptors (CRF1Rs) in the central amygdala (CeA).
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DOI：
10.1016/j.neuropharm.2013.09.025
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发表时间：
2014-02
影响因子：
4.7
通讯作者：
Gilpin NW
中科院分区：
文献类型：
--
作者：
Baiamonte BA;Valenza M;Roltsch EA;Whitaker AM;Baynes BB;Sabino V;Gilpin NW
由于烟草使用对社会产生巨大的负面健康和经济影响，因此找出导致过度使用烟草的因素至关重要。这些因素包括戒烟后出现的厌恶性戒断症状，并可能包括伤害性加工的增加。中央杏仁核 (CeA) 中的促肾上腺皮质激素释放因子 (CRF) 信号在以下方面发挥重要作用：(1) 疼痛的中枢处理；(2) 过量使用尼古丁导致尼古丁依赖；(3) 调节停止烟草暴露后出现的厌恶症状。在这里，我们描述了三个实验，其中主要假设是 CeA 中的 CRF/CRF1 受体 (CRF1R) 信号传导介导尼古丁戒断引起的依赖尼古丁的大鼠伤害感受敏感性的增加。在实验 1 中，从慢性间歇性（14 小时/天）尼古丁蒸气中撤出的尼古丁依赖大鼠在哈格里夫斯试验中表现出对疼痛热刺激的后爪撤回潜伏期缩短，并且通过全身施用 CRF1R 拮抗剂 R121919 减弱了这种效应。在实验 2 中，从尼古丁蒸气中撤出的尼古丁依赖大鼠表现出 CeA 中 CRF 和 CRF1R mRNA 的强劲增加。在实验 3 中，CeA 内施用 R121919 仅减少尼古丁依赖性大鼠的热伤害感受。总的来说，这些结果表明尼古丁依赖会增加 CeA 中的 CRF/CRF1R 信号传导，从而介导戒断引起的对疼痛刺激的敏感性增加。未来的研究将基于这些发现，探索尼古丁戒断引起的疼痛阈值降低通过 CRF/CRF1R 信号通路驱动尼古丁过量使用的假设。
Because tobacco use has a large negative health and financial impact on society, it is critical to identify the factors that drive excessive use. These factors include the aversive withdrawal symptoms that manifest upon cessation of tobacco use, and may include increases in nociceptive processing. Corticotropin-releasing factor (CRF) signalling in the central amygdala (CeA) has been attributed an important role in: (1) central processing of pain, (2) excessive nicotine use that results in nicotine dependence, and (3) in mediating the aversive symptoms that manifest following cessation of tobacco exposure. Here, we describe three experiments in which the main hypothesis was that CRF/CRF1 receptor (CRF1R) signalling in the CeA mediates nicotine withdrawal-induced increases in nociceptive sensitivity in rats that are dependent on nicotine. In Experiment 1, nicotine-dependent rats withdrawn from chronic intermittent (14-h/day) nicotine vapor exhibited decreased hindpaw withdrawal latencies in response to a painful thermal stimulus in the Hargreaves test, and this effect was attenuated by systemic administration of the CRF1R antagonist, R121919. In Experiment 2, nicotine-dependent rats withdrawn from nicotine vapor exhibited robust increases in mRNA for CRF and CRF1Rs in CeA. In Experiment 3, intra-CeA administration of R121919 reduced thermal nociception only in nicotine-dependent rats. Collectively, these results suggest that nicotine dependence increases CRF/CRF1R signalling in the CeA that mediates withdrawal-induced increases in sensitivity to a painful stimulus. Future studies will build on these findings by exploring the hypothesis that nicotine withdrawal-induced reduction in pain thresholds drive excessive nicotine use via CRF/CRF1R signalling pathways.
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影响因子：
3.3
作者：
Ji, Guangchen;Fu, Yu;Ruppert, Katherine A.;Neugebauer, Volker
通讯作者：
Neugebauer, Volker
DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
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作者：
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影响因子：
2.5
作者：
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影响因子：
6
作者：
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