Irritable Bowel Syndrome (IBS) remains a common and challenging syndrome for clinicians. It is defined by recurrent symptoms of abdominal pain or discomfort associated with alterations in bowel habits, in the absence of a detectable structural or inflammatory change in the colon. The pain, discomfort, and impairment from IBS often lead to healthcare medical consultation and workplace absenteeism, and associated economic costs. The causes of IBS and effectiveness of treatment have remained elusive. Although opiates have remained to be the drugs of choice for treating patients with severe pain and a few receptor modulators are marketed for treatment of IBS in recent years, there has been concern about the safety of these drugs. Electroacupuncture (EA), a complementary modality, has been used extensively for treatment of various painful conditions and gastrointestinal diseases. The mechanisms of acupuncture are not well understood, however, and one of the major problems impeding this understanding is a lack of proper experimental models. Recently, we have developed a model of EA-induced analgesia in rats with chronic visceral hyperalgesia (CVH). The objective of this application is to evaluate the effect of EA visceral anti- hyperalgesia and its mechanism in a rat model of CVH. We hypothesize that EA reverses the enhanced excitability of colon specific primary sensory neurons which is at least in part mediated by inhibition of endogenous hydrogen sulfide signaling, thus alleviates CVH. To test this hypothesis, we propose the following specific aims:
Specific Aim 1 is to evaluate the acute and short-term effects of EA on nociceptive responses to colorectal distention in rats with CVH;
Specific Aim 2 is to determine ionic and molecular basis for EA-mediated desensitization of primary sensory neurons in rats with CVH;
and Specific Aim 3 is to determine the role of H2S signaling pathway in EA-mediated analgesia in rats with CVH. We believe that our studies on cellular activity, gene expression, and enzymatic activity in peripheral sensory neurons may open new era towards ionic and molecular understanding of EA treatment in CVH. This added knowledge will provide physicians with an increased clinical acceptance of EA in patients with functional bowel diseases.
Chronic visceral hyperalgesia occurs frequently in patients with functional bowel diseases and has not been controlled adequately. Electroacupuncture has been used for millennia to treat pain. This study will evaluate the effects and mechanisms of electroacupuncture on such pain in a rat model of chronic visceral hypersensitivity and the success of the proposed study will greatly advance the management of chronic visceral pain.
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