Chronic pain and alcohol use disorder (AUD) are highly comorbid, and patients with chronic pain are more likely to meet the criteria for AUD. Evidence suggests that both conditions alter similar brain pathways, yet this relationship remains poorly understood. Prior work shows that the anterior insular cortex (AIC) is involved in both chronic pain and AUD. However, circuit-specific changes elicited by the combination of pain and alcohol use remain understudied. The goal of this work was to elucidate the converging effects of binge alcohol consumption and chronic pain on AIC neurons that send projections to the dorsolateral striatum (DLS). Here, we used the Drinking-in-the-Dark (DID) paradigm to model binge-like alcohol drinking in mice that underwent spared nerve injury (SNI), after which whole-cell patch-clamp electrophysiological recordings were performed in acute brain slices to measure intrinsic and synaptic properties of AIC->DLS neurons. In male, but not female, mice, we found that SNI mice with no prior alcohol exposure consumed less alcohol compared with sham mice. Electrophysiological analyses showed that AIC->DLS neurons from SNI–alcohol male mice displayed increased neuronal excitability and increased frequency of miniature excitatory postsynaptic currents. However, mice exposed to alcohol prior to SNI consumed similar amounts of alcohol compared with sham mice following SNI. Together, our data suggest that the interaction of chronic pain and alcohol drinking have a direct effect on both intrinsic excitability and synaptic transmission onto AIC->DLS neurons in mice, which may be critical in understanding how chronic pain alters motivated behaviors associated with alcohol.

慢性疼痛和酒精使用障碍 (AUD) 具有高度共病性，慢性疼痛患者更有可能符合 AUD 标准。有证据表明，这两种情况都会改变相似的大脑通路，但人们对这种关系仍然知之甚少。先前的研究表明，前岛叶皮质 (AIC) 与慢性疼痛和 AUD 都有关系。然而，疼痛和饮酒相结合引起的特定回路的变化仍未得到充分研究。这项工作的目标是阐明酗酒和慢性疼痛对向背外侧纹状体 (DLS) 发送投射的 AIC 神经元的共同影响。在这里，我们使用黑暗中饮酒（DID）范例来模拟遭受神经损伤（SNI）的小鼠的暴饮暴食，然后在急性脑切片中进行全细胞膜片钳电生理记录测量 AIC->DLS 神经元的内在和突触特性。在雄性小鼠（而非雌性小鼠）中，我们发现与假小鼠相比，之前没有接触过酒精的 SNI 小鼠消耗的酒精较少。电生理学分析表明，SNI-酒精雄性小鼠的 AIC->DLS 神经元表现出神经元兴奋性增加和微型兴奋性突触后电流频率增加。然而，在 SNI 之前接触酒精的小鼠与 SNI 之后的假小鼠消耗的酒精量相似。总之，我们的数据表明，慢性疼痛和饮酒的相互作用对小鼠 AIC->DLS 神经元的内在兴奋性和突触传递有直接影响，这对于理解慢性疼痛如何改变与酒精相关的动机行为可能至关重要。