Corticotropin-releasing factor induces rectal hypersensitivity after repetitive painful rectal distention in healthy humans

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Abstract
Rectal hypersensitivity induced by repetitive rectal distention (RRD) is reported to be a response specific to patients with irritable bowel syndrome (IBS), and is not observed in healthy controls. We evaluated the rectal pain threshold (PT) and determined whether intravenous corticotropin-releasing factor (CRF) induces rectal hypersensitivity after RRD in healthy humans, that is, whether it mimics the response observed in IBS patients. A double-blind placebo-controlled study design (CRF or vehicle) was used. In the first experiment, PT (mmHg) induced by ramp distention was measured by a barostat. Then CRF (100 µg, n = 5) or vehicle (n = 6) was injected intravenously (iv) followed by RRD, consisting of phasic distentions with sensory tracking, which lasted until the subjects had complained of pain six times. After RRD, PT was measured again. In another experiment, PT was measured, and then CRF (n = 5) or vehicle (n = 5) was injected iv. After 45 min, ramp distention was again induced to determine PT. In the placebo group, PT was not modified by RRD (before RRD, 33.0 ± 6.8; after RRD, 33.4 ± 4.5), while it was significantly reduced in the CRF-treated group (before RRD, 32.9 ± 9.0; after RRD, 26.1 ± 7.9, P < 0.05). On the other hand, CRF or vehicle without RRD did not alter PT (before iv-CRF, 35.2 ± 4.2; after iv-CRF, 35.3 ± 4.9; before iv-vehicle, 34.5 ± 7; after iv-vehicle, 35.5 ± 6.8). These results indicate that CRF modifies rectal sensation in healthy humans and mimics an IBS-specific visceral response, suggesting the possible contribution of CRF to the pathogenesis of IBS.