Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and altered bowel function (diarrhea and/or constipation). IBS is estimated to effect 20% of the United States population. Although the pathophysiology of IBS is unknown, visceral hypersensitivity (i.e., decreased pain thresholds in response to gut distension) is a clinical marker of the disorder present in the majority of patients with IBS. The mechanisms that lead to chronic visceral hypersensitivity, however, are currently unknown. Our laboratory has acquired evidence that patients with IBS also display somatic hypersensitivity in response to experimental thermal pain stimuli. These new findings differ from previous investigations that indicated IBS-associated hypersensitivity is limited to the gut. In contrast, our data suggest that IBS is characterized by more widespread alterations in central pain processing. Based on our preliminary data, we propose the novel, mechanistic hypothesis that IBS patients have a generalized but graded hypersensitivity to somatic nociceptive stimuli. We anticipate that this somatic hypersensitivity is somatotopically organized such that the lower dermatomes that share viscerosomatic convergence with the colon demonstrate the greatest hypersensitivity. Moreover, we propose that the hypersensitivity will be greater for deep, tonic stimuli than for superficial, brief stimuli. Importantly, no investigator to date has attempted to systematically characterize perceptual and physiological responses to multiple somatic pain stimuli among patients with IBS. Therefore, we propose the following specific aims.
Specific Aim 1 : To test for differences in somatic hypersensitivity between patients with IBS compared to controls across spatial areas that provide spinal input at differing levels. In order to accomplish this aim, we will assess perceptual responses to four well-validated experimental somatic pain stimuli (thermal pain, pressure pain, cold pressor pain, ischemic pain) across three body sites (forearm, abdomen, leg).
Specific Aim 2 : To test for differences between patients with IBS compared to controls as a function of the characteristics of the pain stimuli (deep vs. superficial, spatial area stimulated).
Specific Aim 3 : To characterize differences in physiological responses to experimental pain stimuli between IBS patients and controls and to examine contributions of physiological responses to pain perception. In order to accomplish this aim, we will assess cardiovascular and neuroendocrine responses to thermal, mechanical, cold pressor, and ischemic pain stimuli.
Specific Aim 4 : To establish the clinical relevance of somatic pain responses among IBS patients by determining whether responses to experimental pain stimuli predict variability in IBS patients' scores on the Functional Bowel Disorder Severity Index.
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