Project 1 - Effect of Electroacupuncture on Visceral Sensation in a Rat Model

肠易激综合征(IBS)是一种常见的胃肠道疾病，以反复发作为特征。 腹痛和排便障碍。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 发病机制。5-羟色胺(5-羟色胺)在胃肠道中含量丰富，是主要的神经肽之一。 参与IBS的发病机制。在啮齿动物模型中，成年期持续性内脏痛觉过敏 新生儿期应激源引起的，如新生儿母体分离和直肠气囊 膨胀。我们之前已经报道过，早期生活应激源可以导致对 肠道神经系统中的5-羟色胺能通路。理论上，内脏痛觉过敏和肠易激 证候可通过逆转或抑制增强的5-羟色胺能通路活性来治疗。 不幸的是，IBS的治疗一直令人失望。尽管一些5-羟色胺受体调节剂 近年来，这些药物被用于治疗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状况和 中医胃肠病。根据中医理论，最多的是 肠易激综合征的常见病因是肝郁攻脾，导致胃肠功能障碍 脾的运化功能。这是一种以证候为特征的状态 反复腹痛、腹泻以及抑郁和焦虑等心理状况。基座 论中医原理--《黄帝内经》是最古老的中医 书中提到，应“内治本病，外治针灸”。 我们以前的研究表明，电针(EA)产生长时间的抗炎和 完全弗氏佐剂(CFA)诱导的炎性痛敏大鼠的抗痛敏作用。它 已有报道称，电针诱导的抗炎和抗痛觉过敏涉及功能调节 在神经内分泌系统中，包括5-羟色胺能系统。因此，针灸可能是一种很有前途的 治疗肠易激综合征。 本研究旨在探讨电针的内脏抗痛觉过敏作用及其机制。 内脏痛觉过敏模型。我们假设电针调节中央处理和外周 信号在内脏伤害性通路中发挥作用，从而减轻内脏痛觉过敏。具体的 这项研究的目的是： 1.观察电针对内脏痛大鼠行为及内脏运动反应的影响。 内脏痛觉过敏。 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.电针对中缝背核和中缝核内5-羟色胺能活动的影响 内脏痛觉过敏大鼠中枢下行抑制通路的中继性中枢--大脑皮层。

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.