Functional Bowel Disorders in Chinese Medicine

肠易激综合征（IBS）是一种常见的胃肠道疾病，其特征是反复腹痛和排便障碍。肠易激综合征的确切发病机制尚不清楚，但越来越多的证据表明内脏痛觉过敏和心理社会应激在发病机制中起重要作用。5-羟色胺（5-HT）在胃肠道中含量丰富，是参与IBS发病的主要神经肽之一。在啮齿类动物模型中，新生儿期的应激源如新生儿母亲分离和直肠球囊扩张可诱导成年期持续性内脏痛觉过敏。我们以前曾报道过早期生活应激可导致肠神经系统胆碱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胆碱能通路的增强活性来治疗。不幸的是，IBS的医学治疗一直令人失望。尽管近年来有几种5-HT受体调节剂上市用于治疗IBS，但人们一直担心这些药物的安全性。 另一方面，针灸已被广泛用于治疗各种疼痛的条件和胃肠道疾病的传统中医。根据中医理论，IBS最常见的病因是“肝郁脾虚，脾运化功能失调”。这是一种以反复腹痛、腹泻和心理状况如抑郁和焦虑综合征为特征的疾病。根据中医的原则，正如最古老的中医书《黄帝内经》所述，应该“内用药物治疗疾病，外用针灸治疗”。 我们以前的研究表明，电针对完全弗氏佐剂（CFA）诱导的炎性痛觉过敏大鼠产生持久的抗炎和抗痛觉过敏作用。已有研究表明，EA诱导的抗炎和抗痛觉过敏作用涉及神经内分泌系统的功能调节，包括肾上腺素能系统。因此，针灸可能是一种有前途的治疗IBS的方法。 本研究旨在观察电针对内脏痛敏大鼠的抗内脏痛敏作用及其机制。我们推测，电针调节内脏伤害性通路的中枢处理和外周信号功能，从而加重内脏痛觉过敏。这项研究的具体目标是： 1.目的：观察电针对内脏痛敏大鼠行为学和内脏神经反应的影响。 2.研究电针对内脏大出血大鼠结肠粘膜胆碱能信号的影响， 痛觉过敏 3.目的：观察电针对内脏大痛大鼠脊髓水平胆碱能活动的影响， 痛觉过敏 4.目的：观察电针对内脏痛觉过敏大鼠中缝背核和中缝大核中枢下行抑制通路的中继中枢胆碱能活动的影响。

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.