Kappa opioid receptor blockade in the nucleus accumbens shell prevents sex-dependent alcohol deprivation effect induced by inflammatory pain. Issue 1 (January 2022)

• Record Type: Journal Article
• Authors: Lorente, Jesús D.; Cuitavi, Javier; Campos-Jurado, Yolanda; Montón-Molina, Raquel; González-Romero, Jose L.; Hipólito, Lucía
• Is Part Of: Pain. Volume 163:Issue 1(2022)
• Publication Date: 2022-01
• Subjects: Norbinaltorphimine -- Kappa opioid receptor -- Nucleus accumbens shell -- Inflammatory pain -- AUD -- Alcohol deprivation effect -- Sex; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000002332
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: 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. Abstract : Only female rats injected with complete Freund adjuvant during a forced abstinence period showed increased alcohol consumption during the reintroduction phase accompanied by increased anxiety-like behaviour. Norbinaltorphimine-microinjected intranucleus accumbens shell impaired inflammatory pain relapse-like behaviour showed by complete Freund adjuvant-injected female rats.