Water avoidance stress induces visceral hyposensitivity through peripheral corticotropin releasing factor receptor type 2 and central dopamine D2 receptor in rats

Background Water avoidance stress (WAS) is reported to induce functional changes in visceral sensory function in rodents, but the results which have been demonstrated so far are not consistent, i.e., hypersensitivity or hyposensitivity. We determined the effect of WAS on visceral sensation and evaluated the mechanisms of the action. Methods Visceral sensation was assessed by abdominal muscle contractions induced by colonic balloon distention, i.e., visceromotor response (VMR), measured electrophysiologically in conscious rats. The electromyogram electrodes were acutely implanted under anesthesia on the day of the experiment. The threshold of VMR was measured before and after WAS for 1 h. To explore the mechanisms of WAS‐induced response, drugs were administered 10 min prior to the initiation of WAS. Key Results WAS significantly increased the threshold of VMR, and this effect was no longer detected at 24 h after. Intraperitoneal injection of astressin2‐B (200 μg/kg), a corticotropin releasing factor (CRF) receptor type 2 antagonist abolished the response by WAS. Subcutaneous (sc) injection of sulpiride (200 mg/kg), a dopamine D2 receptor antagonist blocked the response, while sc domperidone (10 mg/kg), a peripheral dopamine D2 receptor antagonist did not alter it. Naloxone (1 mg/kg, sc), an opioid antagonist did not modify it either. Conclusions & Inferences WAS induced visceral hyposensitivity through peripheral CRF receptor type 2 and central dopamine D2 receptor, but not through opioid pathways. As altered pain inhibitory system was reported to be observed in the patients with irritable bowel syndrome, CRF and dopamine signaling might contribute to the pathophysiology. Water avoidance stress‐induced visceral hyposensitivity in rats and this response was mediated through peripheral corticotropin releasing factor receptor type 2 and central dopamine D2 receptor.