Functional Bowel Disorders in Chinese Medicine

描述(申请人提供)：肠易激综合征(IBS)是一种常见的胃肠道疾病，以反复腹痛和肠道运动障碍为特征。IBS的确切机制尚不清楚，但越来越多的证据表明，内脏痛觉过敏和心理社会应激在其发病机制中起着重要作用。5-羟色胺(5-HT)在胃肠道中含量丰富，是IBS发病机制中的主要神经肽之一。在啮齿动物模型中，新生期应激源如新生儿母体分离和直肠气囊扩张可诱导成年期持续性内脏痛觉过敏。我们以前已经报道过，早期生活应激源可以导致肠道神经系统5-羟色胺能通路的反应性增强。从理论上讲，内脏痛觉过敏和肠易激综合征可以通过逆转或抑制增强的5-羟色胺能通路的活性来治疗。不幸的是，IBS的治疗一直令人失望。尽管近年来一些5-羟色胺受体调节剂被用于治疗IBS，但这些药物的安全性一直令人担忧。 另一方面，针灸在中医中被广泛用于治疗各种疼痛情况和胃肠道疾病。根据中医理论，IBS最常见的原因是肝气郁结攻脾，导致脾的运输和转化功能障碍。这是一种以反复腹痛、腹泻以及抑郁和焦虑等心理状况为特征的症状。根据中医的原理，正如最古老的中医著作《黄帝内经》中所说的那样，一个人应该“以药内治，针灸外治”。我们以前的研究表明，电针(EA)对完全弗氏佐剂(CFA)诱导的炎性痛敏大鼠具有持久的抗炎和抗痛敏作用。有报道称，电针诱导的抗炎和抗痛敏作用涉及神经内分泌系统包括5-羟色胺能系统的功能调节。因此，针灸可能是一种很有前途的治疗IBS的方法。本研究旨在探讨电针对内脏痛觉过敏大鼠的内脏抗痛敏作用及其机制。我们假设电针调节内脏伤害性通路的中枢处理和外周信号功能，从而减轻内脏痛觉过敏。这项研究的具体目的是： 1.观察电针对内脏痛觉过敏模型大鼠行为和内脏运动反应的影响。 2.电针对内脏损伤大鼠结肠黏膜5-羟色胺能信号转导的影响 痛觉过敏。 3.电针对内脏损伤大鼠脊髓水平5-羟色胺能活动的影响 痛觉过敏。 4.观察电针对内脏痛觉过敏大鼠中枢下行抑制通路的传递中枢--中缝背核和中缝大核5-羟色胺能活性的影响。

DESCRIPTION (provided by applicant): Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is characterized by recurrent abdominal pain and disturbance in bowel movements. The exact mechanism of IBS is poorly understood but mounting evidence suggests that visceral hyperalgesia and psychosocial stress play important roles in the pathogenesis. Serotonin (5-HT) is abundant in gastrointestinal tract and one of the major neuropeptides involved in pathogenesis of IBS. In rodent models, persistent visceral hyperalgesia in the adulthood can be induced by stressors during neonatal period such as neonatal maternal separation and rectal balloon distension. We have previously reported that early life stressors can lead to enhanced responsiveness of serotoninergic pathway in enteric nervous system. Theoretically, visceral hyperalgesia and irritable bowel syndrome may be treated by reversal or inhibition of enhanced activity of serotoninergic pathway. Unfortunately, medical treatment of IBS has been disappointing. Although a few 5-HT receptor modulators are marketed for treatment of IBS in recent years, there has been concern about the safety of these drugs. On the other hand, acupuncture has been used extensively for treatment of various painful conditions and gastrointestinal diseases in Traditional Chinese Medicine. According to Chinese medical theories, the most common cause of IBS is the "stagnation of liver energy attacking the spleen and resulting in dysfunction of the transportation and transformation function of the spleen". This is a condition characterized by a syndrome of recurrent abdominal pain, diarrhea and psychological conditions such as depression and anxiety. Based on the principle of TCM, as mentioned in the Yellow Emperor's Inner Classics, the most ancient TCM medical book, one should "use herbs to treat the illness internally and acupuncture to treat externally". Our previous studies have revealed that electroacupuncture (EA) produces prolonged anti-inflammatory and anti-hyperalgesic effects in rats with complete Freund's adjuvant (CFA)-induced inflammatory hyperalgesia. It has been reported that EA-induced anti-inflammation and anti-hyperalgesia involves modulation of functions in the neuroendocrine system including serotoninergic system. Thus, acupuncture may be a promising treatment for IBS. The objective of this study is to evaluate the visceral anti-hyperalgesic effect of EA and its mechanism in a rat model of visceral hyperalgesia. We hypothesize that EA modulates the central processing and peripheral signaling functions in visceral nociceptive pathways, and thereby alleviates visceral hyperalgesia. The specific aims of the study are: 1. To determine the effect of EA on behavioral and visceromotor response to visceral pain in rat model of visceral hyperalgesia. 2. To determine the effect of EA on colonic mucosal serotoninergic signaling in rats with visceral hyperalgesia. 3. To determine the effect of EA on serotoninergic activites at spinal cord level in rats with visceral hyperalgesia. 4. To determine the effect of EA on serotoninergic activites in dorsal raphe nucleus and raphe nucleus magnus, the relay centers of central descending inhibitory pathway, in rats with visceral hyperalgesia.