Pain-induced negative affect reduces life quality of patients by increasing psychiatric comorbidities, including
alcohol use disorders (AUDs). Indeed, clinical data suggest
pain as a risk factor to suffer AUDs, predicting relapse drinking in abstinent patients. Here, we analyse the impact of
pain on alcohol relapse and the role of
kappa opioid receptor (KOR) activation in mediating these
pain-induced effects because KORs play an important role in
pain-driven negative affect and AUD. Female and male Sprague-Dawley rats underwent 2 alcohol intermittent access periods separated by a forced abstinence period. The complete
Freund adjuvant model of inflammatory
pain was introduced during abstinence, and alcohol intake before and after alcohol reintroduction was assessed. In addition, we used behavioural approaches to measure stress and memory impairment and biochemical assays to measure KOR expression in abstinence and reintroduction periods. Only female CFA-treated rats increased alcohol intake during the reintroduction period. Concomitantly, this group showed enhanced anxiety-like behaviour and increased KOR expression in the nucleus accumbens shell that was developed during abstinence and remained during the reintroduction period. Finally, KOR antagonist
norbinaltorphimine was administered in the nucleus accumbens shell during abstinence to prevent a
pain-induced alcohol deprivation effect, a phenomenon observed in CFA-female rats. The administration of
norbinaltorphimine effectively blocked a
pain-induced alcohol deprivation effect in female rats. Our data evidenced that inflammatory
pain constitutes a risk factor to increase alcohol consumption during a reintroduction phase only in female rats by the rise and maintenance of stress probably mediated by KOR signalling in the nucleus accumbens.