Neural responses to stress and alcohol cues in individuals with pain with and without alcohol use disorder

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.