Department of Physiology, Louisiana State University Health Sciences Center School of Medicine, New Orleans, Louisiana.
Department of Physiology, Louisiana State University Health Sciences Center School of Medicine, New Orleans, Louisiana; Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center School of Medicine, New Orleans, Louisiana.
Biol Psychiatry. 2024 Feb 1;95(3):207-219. doi: 10.1016/j.biopsych.2023.09.006. Epub 2023 Sep 16.
Exposure to alcohol during adolescence produces many effects that last well into adulthood. Acute alcohol use is analgesic, and people living with pain report drinking alcohol to reduce pain, but chronic alcohol use produces increases in pain sensitivity.
We tested the acute and lasting effects of chronic adolescent intermittent ethanol (AIE) exposure on pain-related behavioral and brain changes in male and female rats. We also tested the long-term effects of AIE on synaptic transmission in midbrain (ventrolateral periaqueductal gray [vlPAG])-projecting central amygdala (CeA) neurons using whole-cell electrophysiology. Finally, we used circuit-based approaches (DREADDs [designer receptors exclusively activated by designer drugs]) to test the role of vlPAG-projecting CeA neurons in mediating AIE effects on pain-related outcomes.
AIE produced long-lasting hyperalgesia in male, but not female, rats. Similarly, AIE led to a reduction in synaptic strength of medial CeA cells that project to the vlPAG in male, but not female, rats. Challenge with an acute painful stimulus (i.e., formalin) in adulthood produced expected increases in pain reactivity, and this effect was exaggerated in male rats with a history of AIE. Finally, CeA-vlPAG circuit activation rescued AIE-induced hypersensitivity in male rats.
Our findings are the first, to our knowledge, to show long-lasting sex-dependent effects of adolescent alcohol exposure on pain-related behaviors and brain circuits in adult animals. This work has implications for understanding the long-term effects of underage alcohol drinking on pain-related behaviors in humans.
青春期接触酒精会产生许多持续到成年期的影响。急性酒精使用具有镇痛作用，有疼痛的人报告说饮酒可以减轻疼痛，但慢性酒精使用会增加疼痛敏感性。
我们测试了慢性青少年间歇性乙醇（AIE）暴露对雄性和雌性大鼠疼痛相关行为和大脑变化的急性和持久影响。我们还使用全细胞电生理学测试了 AIE 对中脑（腹外侧导水管周围灰质[vlPAG]）投射到中央杏仁核（CeA）神经元的突触传递的长期影响。最后，我们使用基于电路的方法（DREADDs [专门由设计药物激活的设计受体]）来测试 vlPAG 投射 CeA 神经元在介导 AIE 对疼痛相关结果的影响中的作用。
AIE 在雄性大鼠中产生了持久的痛觉过敏，但在雌性大鼠中没有。同样，AIE 导致投射到 vlPAG 的中脑 CeA 细胞的突触强度降低，这种情况仅在雄性大鼠中发生，而在雌性大鼠中则没有。成年后接受急性疼痛刺激（即福尔马林）会导致疼痛反应性增加，而有 AIE 病史的雄性大鼠的这种效应更为明显。最后，CeA-vlPAG 电路的激活挽救了雄性大鼠的 AIE 诱导的超敏反应。
我们的研究结果是首次表明，青少年期酒精暴露对成年动物的疼痛相关行为和大脑回路具有持久的性别依赖性影响。这项工作对理解未成年人饮酒对人类疼痛相关行为的长期影响具有重要意义。
