Peripheral mechanisms underlying electroacupuncture analgesia in a rat model of c

描述（由申请人提供）：肠易激综合征（IBS）仍然是临床医生常见且具有挑战性的综合征。该病的定义为反复出现腹痛或不适症状，伴有排便习惯的改变，但未见结肠结构或炎症改变。IBS引起的疼痛、不适和损伤常常导致医疗咨询和旷工，以及相关的经济成本。肠易激综合征的病因和治疗效果仍然难以捉摸。尽管阿片类药物仍然是治疗严重疼痛患者的首选药物，近年来也有一些受体调节剂用于治疗肠易激综合征，但人们一直担心这些药物的安全性。电针（EA）作为一种辅助疗法，已广泛用于治疗各种疼痛状况和胃肠道疾病。然而，针灸的机制还没有被很好地理解，阻碍这种理解的主要问题之一是缺乏适当的实验模型。最近，我们建立了一种ea诱导的慢性内脏痛觉过敏（CVH）大鼠镇痛模型。目的是评价EA内脏抗痛觉过敏在CVH大鼠模型中的作用及其机制。我们假设EA逆转了结肠特异性初级感觉神经元的兴奋性增强，这至少部分是由抑制内源性硫化氢信号介导的，从而减轻了CVH。为了验证这一假设，我们提出了以下具体目的：具体目的1是评估EA对CVH大鼠结肠膨胀伤害性反应的急性和短期影响；特异性目的2是确定ea介导的CVH大鼠初级感觉神经元脱敏的离子和分子基础；特异性目的3是确定H2S信号通路在ea介导的CVH大鼠镇痛中的作用。我们相信，我们对周围感觉神经元细胞活性、基因表达和酶活性的研究可能会为CVH中EA治疗的离子和分子理解开辟新的时代。这些增加的知识将使医生提高对功能性肠病患者EA的临床接受度。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.