Torrey Pines Institute for Molecular Studies, Port St. Lucie, FL, United States. Dr. Mercatelli is now with the University of Ferrara, Italy. Drs. Brunori, Schoch, Ozawa, Toll, and Cippitelli are now with the Florida Atlantic University, Boca Raton, FL, United States.
Pain. 2018 Nov;159(11):2179-2191. doi: 10.1097/j.pain.0000000000001318.
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 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. Spinal nerve ligation and sham-operated rats showed minor or no changes in patterns of acquisition and motivation for nicotine taking. Spinal nerve ligation 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. Spinal nerve ligation 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 spinal nerve ligation rats. These results demonstrate that chronic pain leads to plasticity of nAChRs that do not directly facilitate nicotine addictive behaviors. Instead, nicotine potently decreases allodynia, an effect that could lead to increased nicotine consumption in chronic pain subjects.
吸烟在经历慢性疼痛的个体中尤为明显。这种复杂的关系在分子和行为水平上都理解得很差。在这里，我们描述了旨在了解慢性疼痛状态是否会引起大脑或外周神经的神经适应，这些神经适应是否直接导致对尼古丁成瘾的易感性增加或发展缓解疼痛症状的应对策略的实验。我们发现，结扎大鼠 L5 脊神经导致背根神经节中所有 nAChR 亚基的 mRNA 表达水平显著下调，并且离散亚基的下调具有时间依赖性，尤其是在扣带皮层和杏仁核中。结扎脊神经和假手术大鼠在尼古丁摄取的获取和动机模式上表现出较小或没有变化。当通过与尼古丁相关的线索诱导复用时，结扎脊神经的大鼠也表现出与假动物相似的对尼古丁寻求的易感性，但当通过尼古丁引发引起复用时，它们未能恢复杠杆按压。结扎脊神经和假手术大鼠对尼古丁引起的焦虑样行为和镇痛作用同样敏感；然而，尼古丁在结扎脊神经的大鼠中产生了强烈而持久的抗痛觉过敏作用。这些结果表明，慢性疼痛导致 nAChR 的可塑性，而不会直接促进尼古丁成瘾行为。相反，尼古丁强烈地减轻痛觉过敏，这一作用可能导致慢性疼痛患者尼古丁消费的增加。
