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NEUROREGULATION AND MOTILITY

Corticotropin-releasing factor receptor 1 mediates acute and delayed stress-induced visceral hyperalgesia in maternally separated Long-Evans rats

¹Corticotropin Releasing Factor Research Program, Center for Neurovisceral Sciences and Women's Health, and Digestive Diseases Research Center, Department of Medicine, ²Center for Ulcer Research and Education/Department of Physiology, Psychiatry and Biobehavioral Sciences, and ³Center for Ulcer Research and Education/Department of Psychology, David Geffen School of Medicine, University of California-Los Angeles, and ⁴Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California; and ⁵Stress Neurobiology Laboratory, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia

Submitted 5 November 2004 ; accepted in final form 26 April 2005

In rodents, maternal pup interactions play an important role in programming the stress responsiveness of the adult organism. The aims of this study were 1) to determine the effect of different neonatal rearing conditions on acute and delayed stress-induced visceral sensitivity as well as on other measures of stress sensitivity of the adult animal; and 2) to determine the role of corticotropin-releasing factor receptor (CRF-R) subtype 1 (CRF₁R) in mediating visceral hypersensitivity. Three groups of male Long-Evans rat pups were used: separation from their dam for 180 min daily from postnatal days 2–14 (MS180), daily separation (handling) for 15 min (H), or no handling. The visceromotor responses (VMR) to colorectal distension, stress-induced colonic motility, and anxiety-like behavior were assessed in the adult rats. The VMR was assessed at baseline, immediately after a 1-h water avoidance (WA) stress, and 24 h poststress. Astressin B, a nonselective CRF-R antagonist, or CP-154,526, a selective CRF₁R antagonist, was administered before the stressor and/or before the 24-h measurement. MS rats developed acute and delayed stress-induced visceral hyperalgesia. In contrast, H rats showed hypoalgesia immediately after WA and no change in VMR on day 2. MS rats with visceral hyperalgesia also exhibited enhanced stress-induced colonic motility and increased anxiety-like behavior. In MS rats, both CRF-R antagonists abolished acute and delayed increases in VMR. Rearing conditions have a significant effect on adult stress responsiveness including immediate and delayed visceral pain responses to an acute stressor. Both acute and delayed stress-induced visceral hypersensitivity in MS rats are mediated by the CRF/CRF₁R system.

maternal separation; visceral hypersensitivity; corticotropin-releasing factor receptor antagonists

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