Brain corticotropin-releasing factor signaling: Involvement in acute stress-induced visceral analgesia in male rats

Background Water avoidance stress (WAS) induces a naloxone-independent visceral analgesia in male rats under non-invasive conditions of monitoring. The objective of the study was to examine the role of brain CRF signaling in acute stress-induced visceral analgesia (SIVA). Methods Adult male Sprague-Dawley rats were chronically implanted with an intracerebroventricular (ICV) cannula. The visceromotor response (VMR) to graded phasic colorectal distension (CRD: 10, 20, 40, 60 mm Hg, 20 seconds, 4 minutes intervals) was monitored using manometry. The VMR to a first CRD (baseline) was recorded 5 minutes after an ICV saline injection, followed 1 hour later by ICV injection of either CRF (30, 100, or 300 ng and 1, 3, or 5 mu g/rat) or saline and a second CRD, 5 minutes later. Receptor antagonists against CRF1/CRF2 (astressin-B, 30 mu g/rat), CRF2 (astressin(2)-B, 10 mu g/rat), oxytocin (tocinoic acid, 20 mu g/rat), or vehicle were injected ICV 5 minutes before CRF (300 ng/rat, ICV) or 15 minutes before WAS (1 hour). Key Results ICV CRF (100 and 300 ng) reduced the VMR to CRD at 60 mm Hg by -36.6% +/- 6.8% and -48.7% +/- 11.7%, respectively, vs baseline (P < 0.001), while other doses had no effect and IP CRF (10 mu g/kg) induced visceral hyperalgesia. Astressin-B and tocinoic acid injected ICV induced hyperalgesia and prevented the analgesic effect of ICV CRF (300 ng/rat) and WAS, while astressin(2)-B only blocked WAS-induced SIVA. Conclusions & Inferences These data support a role for brain CRF signaling via CRF2 in SIVA in a model of WAS and CRD likely mediated by the activation of brain oxytocin pathway.