Visceral pain, particularly visceral hyperalgesia such as is associated with the functional bowel disorders like irritable bowel syndrome, is poorly understood. Because functional bowel disorders are characterized by increased sensitivity to gastrointestinal stimulation, pain and discomfort, they represent a visceral hyperalgesia. Increasing interest over the past decade or more has contributed significant knowledge about visceral pain mechanisms. The current application proposes to build on this base of knowledge to develop and characterize models of visceral hyperalgesia that relate closely to clinical conditions typified by irritable bowel syndrome. Specifically, this proposal will focus on examination and characterization of peripheral contributions to the development and maintenance of visceral hyperalgesia.
The first aim will be to develop appropriate models of irritable bowel syndrome and contrast those models with a model of colonic inflammation/colitis. It is hypothesized that changes in the excitability of visceral sensory fibers contribute significantly to development of visceral hyperalgesia and the second aim of this proposal will be in vivo electrophysiological examination of pelvic nerve afferent fiber excitability. Because increases in excitability of pelvic nerve sensory fibers must arise from changes in the function of ion channels or receptors in their cell bodies and terminals, the third aim of this proposal is to study the excitability of identified colon sensory neurons.
These aims are a logical extension of the current project and will continue important investigations into the mechanisms of visceral hyperalgesia. The proposed experiments comprise a quantitative study of visceral hyperalgesia, pelvic nerve sensory afferent fibers and colon sensory neurons that will lead to better understanding of the mechanisms responsible for visceral hyperalgesia.
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