Sharfman Nathan, Gilpin Nicholas W
Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, United States.
Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, United States.
Front Psychiatry. 2021 Nov 4;12:764720. doi: 10.3389/fpsyt.2021.764720. eCollection 2021.
The global COVID-19 pandemic has shone a light on the rates and dangers of alcohol misuse in adults and adolescents in the US and globally. Alcohol exposure during adolescence causes persistent molecular, cellular, and behavioral changes that increase the risk of alcohol use disorder (AUD) into adulthood. It is established that alcohol abuse in adulthood increases the likelihood of pain hypersensitivity and the genesis of chronic pain, and humans report drinking alcohol to relieve pain symptoms. However, the longitudinal effects of alcohol exposure on pain and the underlying CNS signaling that mediates it are understudied. Specific brain regions mediate pain effects, alcohol effects, and pain-alcohol interactions, and neural signaling in those brain regions is modulated by neuropeptides. The CNS melanocortin system is sensitive to alcohol and modulates pain sensitivity, but this system is understudied in the context of pain-alcohol interactions. In this review, we focus on the role of melanocortin signaling in brain regions sensitive to alcohol and pain, in particular the amygdala. We also discuss interactions of melanocortins with other peptide systems, including the opioid system, as potential mediators of pain-alcohol interactions. Therapeutic strategies that target the melanocortin system may mitigate the negative consequences of alcohol misuse during adolescence and/or adulthood, including effects on pain-related outcomes.
全球新冠疫情让美国乃至全球成年人和青少年酒精滥用的发生率及危害暴露无遗。青春期接触酒精会导致持续的分子、细胞和行为变化，增加成年后患酒精使用障碍（AUD）的风险。已证实成年期酗酒会增加痛觉过敏的可能性以及慢性疼痛的发生，而且人们报告称饮酒是为了缓解疼痛症状。然而，酒精接触对疼痛的纵向影响以及介导这种影响的潜在中枢神经系统信号传导尚未得到充分研究。特定脑区介导疼痛效应、酒精效应以及疼痛 - 酒精相互作用，这些脑区的神经信号传导受神经肽调节。中枢神经系统黑皮质素系统对酒精敏感并调节疼痛敏感性，但在疼痛 - 酒精相互作用的背景下，该系统尚未得到充分研究。在本综述中，我们重点关注黑皮质素信号传导在对酒精和疼痛敏感的脑区，尤其是杏仁核中的作用。我们还讨论黑皮质素与其他肽系统（包括阿片系统）的相互作用，将其作为疼痛 - 酒精相互作用的潜在介质。针对黑皮质素系统的治疗策略可能会减轻青春期和/或成年期酒精滥用的负面后果，包括对疼痛相关结局的影响。
