Corticotropin-releasing factor (CRF) 1 receptor (CRF(1)) activation in the brain is a core pathway orchestrating the stress response. Anatomical data also support the existence of CRF signaling components within the colon. We investigated the colonic response to intraperitoneal (ip) injection of cortagine, a newly developed selective CRF(1) peptide agonist. Colonic motor function and visceral motor response (VMR) were monitored by using a modified miniaturized pressure transducer catheter in adult conscious male Sprague-Dawley rats and C57Bl/6 mice. Colonic permeability was monitored by the Evans blue method and myenteric neurons activation by Fos immunohistochemistry. Compared with vehicle, cortagine (10 microg/kg ip) significantly decreased the distal colonic transit time by 45% without affecting gastric transit, increased distal and transverse colonic contractility by 35.6 and 66.2%, respectively, and induced a 7.1-fold increase in defecation and watery diarrhea in 50% of rats during the first hour postinjection whereas intracerebroventricular (icv) cortagine (3 microg/rat) had lesser effects. Intraperitoneal (ip) cortagine also increased colonic permeability, activated proximal and distal colonic myenteric neurons, and induced visceral hypersensitivity to a second set of phasic colorectal distention (CRD). The CRF antagonist astressin (10 mug/kg ip) abolished ip cortagine-induced hyperalgesia whereas injected icv it had no effect. In mice, cortagine (30 microg/kg ip) stimulated defecation by 7.8-fold, induced 60% incidence of diarrhea, and increased VMR to CRD. Stresslike colonic alterations induced by ip cortagine in rats and mice through restricted activation of peripheral CRF(1) receptors support a role for peripheral CRF(1) signaling as the local arm of the colonic response to stress.

Selye’s pioneer the concept of biological stress in 1936 culminating to the identification of the corticotropin releasing factor (CRF) signaling pathways by Vale’s group in the last two decades. The characterization of the 41 amino-acid CRF and other peptide members of the mammalian CRF family, urocortin 1, urocortin 2 and urocortin 3, the cloning of CRF1 and CRF2 receptors, which display distinct affinity for CRF ligands, combined with the development of selective CRF receptor antagonists enable to unravel the importance of CRF1 receptor in the stress-related endocrine (activation of pituitary-adrenal axis), behavioral (anxiety/depression, altered feeding), autonomic (activation of sympathetic nervous system) and immune responses. The activation of CRF1 receptors is also part of key mechanisms through which various stressors impact the gut to stimulate colonic propulsive motor function and to induce hypersensitivity to colorectal distension as shown by the efficacy of the CRF1 receptor antagonists in blunting these stress-related components. The importance of CRF1 signaling pathways in the visceral response to stress in experimental animals provided new therapeutic approaches for treatment of functional bowel disorder such as irritable bowel syndrome, a multifactor functional disorder characterized by altered bowel habits and visceral pain for which stress has been implicated in the pathophysiology and is associated with anxiety-depression in subset of patients.

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Distress is an increasing public health problem. We aimed to investigate the effects of an Iyengar yoga program on perceived stress and psychological outcomes in distressed women and evaluated a potential dose-effect relationship. Seventy-two female distressed subjects were included into a 3-armed randomized controlled trial and allocated to yoga group 1 (n = 24) with twelve 90 min sessions over 3 months, yoga group 2 (n = 24) with 24 sessions over 3 months, or a waiting list control group (n = 24). The primary outcome was stress perception, measured by Cohen Stress Scale; secondary outcomes included state trait anxiety, depression, psychological and physical quality of life (QOL), profile of Mood States, well being, and bodily complaints. After three months, women in the yoga groups showed significant improvements in perceived stress (P = 0.003), state trait anxiety (P = 0.021 and P = 0.003), depression (P = 0.008), psychological QOL (P = 0.012), mood states being (P = 0.007), and bodily complaints well(P = 0.012) when compared to controls. Both yoga programs were similarly effective for these outcomes; however, compliance was better in the group with fewer sessions (yoga group 1). Dose effects were seen only in the analysis of group-independent effects for back pain, anxiety, and depression. These findings suggest that Iyengar yoga effectively reduces distress and improves related psychological and physical outcomes. Furthermore, attending twice-weekly yoga classes was not superior to once-weekly classes, as a result of limited compliance in the twice-weekly group.

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