Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and altered bowel function (diarrhea and/or constipation) that effects up to 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 biological marker of the disorder. The mechanisms that lead to visceral hypersensitivity, however, are currently unknown. As a consequence of our current VA-supported studies, our laboratory has acquired evidence that patients with IBS and visceral hypersensitivity also have cutaneous 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. Rather, our data suggest that patients with IBS have alterations in central pain processing mechanisms that may represent the underlying pathophysiological basis for visceral and cutaneous hypersensitivity. Based on our preliminary data, we propose that alterations in spinal processing mechanisms are similar in patients with IBS to those that have been described for patients with other chronic pain disorders. Cutaneous hypersensitivity is also seen in other chronic pain conditions such as fibromyalgia where altered central pain processing mechanisms have been shown to be responsible for maintaining hypersensitivity. In our current proposal, we hypothesize that IBS patients have increased peripheral and central afferent processing of nociceptive cutaneous and visceral stimuli.
Our objectives are as follows:
- Specific Objective #1. To determine if lidocaine applied to the rectum decreases visceral hyperalgesia, as tested by nociceptive rectal distension.
- Specific Objective #2. To determine if lidocaine applied to the rectum decreases cutaneous heat hyperalgesia to test for the presence or absence of central hyperalgesia in IBS patients.
- Specific Objective #3. To determine the relationships between doses of IV lidocaine, serum levels of IV lidocaine, and their anti-hyperalgesic effects, as tested by rectal distension and cutaneous heat stimulation.
Specific Objective #4. To determine the effect of rectal lidocaine on clinical pain and clinical symptoms of IBS.
The proposed studies will test the central hypothesis using well-controlled sensory stimuli designed to separately evaluate central and peripheral mechanisms. The objectives will be accomplished by systematically applying and comparing pharmacological and psychophysical studies to IBS patients and controls. This application is an extension of the principal investigator’s current VA Advanced Career Development Award that examines the neurobiology of visceral hypersensitivity in Persian Gulf veterans who returned home with chronic abdominal pain. The proposed Clinical Research Program will study afferent mechanisms of visceral and cutaneous hypersensitivity in veterans with IBS. Our laboratory is uniquely positioned to use our expertise in psychophysical and pharmacologic evaluation of patients with fibromyalgia to study patients with IBS. The results of this current proposal will lead to larger clinical trials with sodium-channel blockers (i.e., lidocaine, mexiletine) as potential therapeutic agents for veterans with IBS.
Purpose
