Colorectal distension (CRD) is a well-characterized model of visceral nociception, which we adapted to the mouse. CRD reproducibly evoked contractions of the abdominal musculature [visceromotor response (VMR)], which was graded to stimulus intensity. The magnitude of VMR was greater in male C57BL6 and female 129S6 mice than in male 129S6 and B6.129 mice. In 129S6, C57BL6, and B6.129 mice strains, VMR was reduced dose dependently by morphine (1-10 mg/kg) and by the -opioid agonist U-69593 (0.2-2 mg/kg), although U-69593 was significantly less potent in C57BL6 mice. In additional experiments, the VMR was recorded from adult male 129S6 mice before and after intracolonic administration of various irritants. Only 30% ethanol significantly enhanced responses to CRD. The colon hyperalgesia persisted for 14 days and was associated with a significant shift of the morphine doseresponse function to the left. We believe this will be a useful model for study of visceral nociception and hyperalgesia, including studies of transgenic mice with mutations relevant to pain. colon; visceral pain; knockout mice; strain; gender; -opioid PAIN IS THE MOST COMMON REASON patients seek care from a physician, and the majority of visits are for pain of visceral origin. Current knowledge about mechanisms of pain has been derived from studies of somatic, principally cutaneous pain. Visceral pain has been less well studied, in part, because of more difficult access to visceral structures. Additionally, stimuli that are painful when applied to the skin, such as burning, crushing, and cutting, evoke no pain when applied to most visceral structures. Furthermore, there is growing evidence that the mechanisms of visceral and cutaneous pain are different (8,19). Certainly, the characteristics of these pains are different; visceral pain is diffuse, poorly localized, and referred to overlying structures (see Refs. 7 and 46 for reviews).Balloon distension of hollow organs, such as the colon, stomach, or urinary bladder produces pain in humans and quantifiable behavioral and autonomic responses in nonhuman animals. These responses have been most extensively characterized for colorectal distension (CRD) in the rat. When applied to rats at pressures comparable to those that produce pain in humans, CRD is aversive and produces tachycardia, pressor effects, contraction of the abdominal musculature, activation of afferent (sensory) fibers in the pelvic nerve, and activation of second-order neurons in the dorsal horn of the spinal cord (45,46,52).The availability of genetically modified mice has increased interest in the mouse as a nonhuman experimental animal. Numerous mice have been generated with mutations relevant to the study of pain; most have been tested in cutaneous models of nociception only. Some transgenic mice have been tested using the intraperitoneal acetic acid model of visceral nociception (writhing test); however, a limited understanding of the underlying structures and sensory neurons activated in this model confounds interpretation of resul...

No abstract