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

Abstract

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 μg/rat) or saline and a second CRD, 5 minutes later. Receptor antagonists against CRF1/CRF2 (astressin‐B, 30 μg/rat), CRF2 (astressin2‐B, 10 μg/rat), oxytocin (tocinoic acid, 20 μg/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 µg/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 astressin2‐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.

Activation of CRF1 receptors expressed in brainstem autonomic nuclei stimulates colonic enteric neurons and secreto‐motor function in male rats

“…The 4V chronically cannulated rats were divided into 7 groups ( 4 showing maximal efficiency to influence gastrointestinal function and prevent CRF action. [30][31][32] Fecal pellets and diarrhea were monitored for 1 h after the last injection, then rats were euthanized by decapitation, the colon was harvested for whole-mount preparation of pC and dC enteric plexus followed by immunohistochemistry.…”

Epigenetic Mechanisms in Irritable Bowel Syndrome

“…Many studies support an important role for stress in the IBS pathophysiology and symptoms ( 8 ). The stress-induced activation or augmentation of the CRF and HPA axis systems has been associated with visceral hypersensitivity, an important feature of IBS, in animal models ( 55 – 58 ). IBS patients have a greater reactivity to stress compared to healthy subjects, as manifested by a dysregulated HPA axis response, enhanced visceral perception and gut motility, among other findings ( 59 – 61 ).…”

Functional and Anatomical Characterization of Corticotropin-Releasing Factor Receptor Subtypes of the Rat Spinal Cord Involved in Somatic Pain Relief

“…In addition to somatic pain, CRF seems to intervene in the regulation of visceral pain [ 8 ]. Indeed, intracerebroventricular administration of CRF resulted in a significant inhibition of the nociceptive visceromotor response to colorectal distension [ 9 ]. Moreover, systemic application of a CRF-R2 agonist inhibited an increase in the spinal activity marker ERK1/2 and prevented a nociceptive visceromotor response to colorectal distension [ 10 ].…”