Radoman Milena, McGowan Colleen, Heilner Emily, Lacadie Cheryl, Sinha Rajita
Yale Stress Center, Department of Psychiatry, Yale University School of Medicine, Yale Stress Center, New Haven, Connecticut, USA.
Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut, USA.
Addict Biol. 2024 Dec;29(12):e70010. doi: 10.1111/adb.70010.
Pain and alcohol use disorder (AUD) frequently co-occur, but the underlying neurobiology is not well-understood. Although many studies have reported disruptions in stress and reward cue-elicited neural reactivity and heightened alcohol craving in individuals with AUD, little is known about these constructs among patients who experience pain. Here, individuals with pain (Pain+, n = 31) and without pain (Pain-, n = 37) completed a well-validated functional magnetic resonance imaging (fMRI) paradigm involving stress (S), alcohol (A) and neutral (N) cue exposure with repeated alcohol craving assessments. Using whole-brain, voxel-based analyses (p < 0.001, whole-brain cluster correction at α < .05), the Pain+ versus Pain- group evidenced greater dorsal anterior cingulate cortex and left amygdala hyperactivation during N, but hypoactivation during the S-N contrast. Additionally, Pain+ exhibited blunted right anterior insular cortex (AIC) during S-N and blunted anteromedial thalamus and left AIC with hyperactive orbitofrontal cortex (OFC) during A-N. Exploratory analyses further revealed that individuals with pain and AUD (n = 17) relative to pain alone (n = 14) showed hyperactive bilateral AIC and hypoactive right dorsal caudate during A-N. Alcohol cue-induced craving, significantly higher in Pain+ (p = 0.03), correlated with blunted right AIC and OFC responses during A-N. In sum, these results provide first evidence of heightened alcohol cue-elicited craving and disrupted stress- and alcohol cue-reactivity within corticostriatal-limbic regions implicated in negative affect and preoccupation/anticipation stages of AUD in those with pain and with comorbid pain and AUD. Future investigations of pain-AUD interaction are needed that include systematic pain assessment and longitudinal designs with larger sample sizes.
疼痛与酒精使用障碍（AUD）经常同时出现，但其潜在的神经生物学机制尚未完全明确。尽管许多研究报告了AUD患者在应激和奖励线索引发的神经反应方面存在紊乱，且对酒精的渴望增强，但对于经历疼痛的患者中这些结构的了解却很少。在此，有疼痛的个体（疼痛组，n = 31）和无疼痛的个体（非疼痛组，n = 37）完成了一项经过充分验证的功能磁共振成像（fMRI）范式，该范式包括应激（S）、酒精（A）和中性（N）线索暴露以及重复的酒精渴望评估。使用基于体素的全脑分析（p < 0.001，α < 0.05的全脑簇校正），疼痛组与非疼痛组相比，在暴露于N线索期间，背侧前扣带回皮质和左侧杏仁核表现出更强的激活，但在S - N对比期间表现为激活不足。此外，在S - N期间，疼痛组右侧前岛叶皮质（AIC）反应迟钝，在A - N期间，前内侧丘脑和左侧AIC反应迟钝，而眶额皮质（OFC）过度活跃。探索性分析进一步显示，与单纯疼痛个体（n = 14）相比，患有疼痛和AUD的个体（n = 17）在A - N期间双侧AIC过度活跃，右侧背侧尾状核激活不足。酒精线索诱发的渴望在疼痛组中显著更高（p = 0.03），与A - N期间右侧AIC和OFC反应迟钝相关。总之，这些结果首次证明了在患有疼痛以及同时患有疼痛和AUD的个体中，酒精线索诱发的渴望增强，且在与AUD的负面影响以及专注/预期阶段相关的皮质纹状体 - 边缘区域内，应激和酒精线索反应受到破坏。未来需要对疼痛 - AUD相互作用进行研究，包括系统的疼痛评估和更大样本量的纵向设计。
