Proopiomelanocortin (POMC)–β‐Endorphin System in the Rat Colon: Expression, Up Regulation by Stress, and Correlation With Stress‐Induced Visceral Analgesia

Abstract

ABSTRACT Background The pituitary proopiomelanocortin (POMC)–β‐endorphin (β‐END) system is activated by hypothalamic corticotropin‐releasing factor (CRF) signaling and stress. We investigated whether this pathway is also expressed in the rat colon, regulated by peripheral CRF and stress, and correlated with stress‐induced visceral analgesia. Methods POMC and the prohormone convertases PC1/3 and PC2 transcripts were assessed by RT‐PCR, and POMC and β‐END localization was examined by immunohistochemistry in the proximal and distal colon of naïve adult male Sprague–Dawley rats. Proximal colonic POMC mRNA was quantified by real‐time quantitative PCR 1 h after intraperitoneal injection of CRF (10 μg/kg) or saline and on day 11 after assessing visceromotor responses (VMRs) to colorectal distension (CRD) using a non‐invasive method in rats subjected to repeated water avoidance stress (rWAS) (1 h/day for 10 days) or control handling. The correlation between POMC gene expression and VMRs was evaluated. Results POMC, PC1/3, and PC2 transcripts were detected in the proximal and distal colon. POMC‐ and β‐END‐immunoreactive cells are localized in the lamina propria and enteric plexuses. CRF increased POMC mRNA expression by 2.5‐fold. rWAS decreased VMRs to CRD in a pressure‐dependent manner, with a reduction of up to 52% at 60 mmHg, and increased POMC expression 10‐fold compared with controls; POMC expression was inversely correlated with cumulative VMRs (r = −0.655, p = 0.034). Conclusions POMC‐β‐END system expression in the rat colonic enteric plexus, together with CRF/stress‐induced upregulation of POMC and its correlation with analgesic responses to CRD, suggests a possible relevance in modulating visceral pain.