Abstract
BACKGROUND: Alcohol analgesia (AA) is a well-established phenomenon and important motivator of pain self-medication with alcohol. Alcohol intoxication produces widespread alterations in many brain areas involved in pain processing. Sex and family history (FH) of problematic alcohol use both influence AA. Investigation of neural response to experimental pain during alcohol intoxication, and potential interactive effects of sex and FH, may clarify important pathways of risk for pain chronicity and alcohol use disorder. METHODS: Subjects (N = 97, Mean age = 26.23, SD = 4.97, 52.26% female, 41.23% FH +) completed two laboratory sessions in which they consumed alcohol (breath alcohol concentration, BrAC = 0.08 g/dL) or placebo (BrAC = 0.00 g/dL) beverages and completed functional magnetic resonance imaging (fMRI) scanning while experiencing painful, thermal sensations. Blood-oxygenation-level-dependent (BOLD) activation during painful stimuli was assessed with a general linear model (GLM; factors: condition, sex, FH). Generalized psychophysical interaction (gPPI) investigated alterations in functional connectivity during heat pain with seed regions with altered BOLD activation in GLM analyses. Potential alcohol-induced cerebrovascular effects were examined using arterial spin labeling. RESULTS: Subjective report of pain during scanning was not found to differ between beverage conditions. No effects of alcohol on cerebral blood flow were detected. Across conditions, we noted widespread activation during noxious stimuli within regions canonically associated with pain processing. Male subjects exhibited significantly less BOLD activation during the alcohol than placebo session in the right dorsolateral prefrontal cortex. No FH effects were identified. Pain-related connectivity with this region was altered with aspects of the frontal, occipital, insular, and supramarginal gyri. CONCLUSION: Alcohol may subtly influence neural processes involved in pain perception, particularly among regions involved in top-down pain modulation uniquely between sexes. These effects may be more visible in interregional indices of brain function. Future investigations of multidimensional neural metrics and at various alcohol doses are needed to further explore mechanisms of AA.