Influence of neuropathic pain on nicotinic acetylcholine receptor plasticity and behavioral responses to nicotine in rats.
Influence of neuropathic pain on nicotinic acetylcholine receptor plasticity and behavioral responses to nicotine in rats.
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DOI：
10.1097/j.pain.0000000000001318
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发表时间：
2018-11
期刊：
影响因子：
7.4
通讯作者：
Cippitelli A
中科院分区：
文献类型：
--
作者：
Brunori G;Schoch J;Mercatelli D;Ozawa A;Toll L;Cippitelli A
在经历慢性疼痛的个人中，吸烟尤其明显。这种复杂的关系在分子和行为水平上都知之甚少。在这里，我们描述了旨在了解慢性疼痛状态是否诱导神经适应进入涉及尼古丁乙酰胆碱受体（nachr）的大脑或周围神经，以及这些神经适应是否直接导致尼古丁成瘾易感性增加或发展应对策略以缓解疼痛症状的实验。我们发现大鼠L5脊神经（SNL）结扎导致背根神经节中所有nAChR亚基mRNA表达水平的显著下调，以及扣带皮层和杏仁核中离散亚基的时间依赖性下调。SNL和假手术大鼠在获取模式和尼古丁摄取动机方面表现出轻微或没有变化。SNL大鼠在尼古丁相关线索诱导下恢复时也表现出与假动物相似的尼古丁寻求脆弱性，但在尼古丁启动诱导下复发时未能恢复杠杆压。SNL大鼠和假大鼠对尼古丁诱导的焦虑样行为和抗感觉反应同样敏感；然而，尼古丁在SNL大鼠中产生了有效而持久的抗异动作用。这些结果表明，慢性疼痛导致nachr的可塑性，但不直接促进尼古丁成瘾行为。相反，尼古丁有效地减少了异位性疼痛，这种效果可能导致慢性疼痛受试者尼古丁摄入量增加。
Tobacco smoking is particularly evident in individuals experiencing chronic pain. This complex relationship is poorly understood at both molecular and behavioral levels. Here we describe experiments aimed at understanding whether a chronic pain state induces neuroadaptations into the brain or peripheral nerves that involve nicotinic acetylcholine receptors (nAChRs) and whether these neuroadaptations directly lead to increased vulnerability to nicotine addiction or to the development of coping strategies to relieve pain symptoms. We found that ligation of the rat L5 spinal nerve (SNL) led to a dramatic downregulation in the mRNA expression levels of all nAChR subunits examined in dorsal root ganglia and a time-dependent downregulation of discrete subunits particularly in the cingulate cortex and the amygdala. SNL and sham-operated rats showed minor or no changes in patterns of acquisition and motivation for nicotine taking. SNL rats also showed similar vulnerability to nicotine seeking as sham animals when reinstatement was induced by nicotine-associated cues but failed to reinstate lever pressing when relapse was induced by nicotine priming. SNL and sham rats were equally sensitive to nicotine-induced anxiety-like behavior and antinociception; however, nicotine produced a potent and long-lasting antiallodynic effect in SNL rats. These results demonstrate that chronic pain leads to plasticity of nAChRs that does not directly facilitate nicotine addictive behaviors. Instead, nicotine potently decreases allodynia, an effect that could lead to increased nicotine consumption in chronic pain subjects.
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影响因子：
3.4
作者：
Cippitelli, Andrea;Ayanwuyi, Lydia O.;Ciccocioppo, Roberto
通讯作者：
Ciccocioppo, Roberto
DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
11.1
作者：
George, Olivier;Ghozland, Sandy;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
10.6
作者：
Alba-Delgado, Cristina;Llorca-Torralba, Meritxell;Berrocoso, Esther
通讯作者：
Berrocoso, Esther
影响因子：
22.4
作者：
Kassel, JD;Stroud, LR;Paronis, CA
通讯作者：
Paronis, CA
影响因子：
4.1
作者：
Gonzalez-Sepulveda, Marta;Pozo, Oscar J.;Valverde, Olga
通讯作者：
Valverde, Olga