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

项目 1 - 电针对大鼠模型内脏感觉的影响

• 批准号: 7688106
• 负责人: BRIAN M BERMAN
• 金额: $ 10.07万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7688106
• 关键词: Abdomen; Abdominal Pain; Acupuncture procedure; Anti-Inflammatory Agents; Anti-inflammatory; Anxiety; Behavioral; Biological Markers; Books; Brain Stem; Carrier Proteins; China; Chinese People; Chinese Traditional Medicine; Colon; Colorectal; Condition; Defecation; Diarrhea; Electroacupuncture; Enteric Nervous System; Enterochromaffin Cells; Enzyme-Linked Immunosorbent Assay; Enzymes; Equilibrium; Esthesia; Evaluation; FOS Protein; FOS gene; Freund' s Adjuvant; Functional disorder; Gastrointestinal Diseases; Gastrointestinal tract structure; Genus Cola; Hand; Herb; Hyperalgesia; Immunohistochemistry; Inflammation; Inflammatory; Irritable Bowel Syndrome; Lead; Life; Liver; Marketing; Mediating; Medical; Mental Depression; Messenger RNA; Modality; Modeling; Neonatal; Nerve; Neuraxis; Neurons; Neuropeptides; Neurosecretory Systems; Nociception; Pain; Pain Threshold; Pathogenesis; Pathway interactions; Peripheral; Pharmaceutical Preparations; Play; Process; Protein Biosynthesis; Proteins; Proto-Oncogene Proteins c-fos; Psychosocial Stress; Rate; Rattus; Recurrence; Reporting; Reverse Transcriptase Polymerase Chain Reaction; Rodent Model; Role; Safety; Serotonin; Serotonin Receptors 5-HT-3; Signal Transduction; Spinal Cord; Spleen; Surrogate Markers; Synapses; Syndrome; System; Transportation; Tryptophan 5-monooxygenase; Visceral; Visceral pain; Western Blotting; base; dorsal horn; dorsal raphe nucleus; ilium; mRNA Expression; maternal separation; protein expression; psychologic; raphe nucleus magnus; receptor; receptor expression; rectal; response; reuptake; serotonin receptor; sham-controlled study; stressor; theories; transmission process

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.

肠易激综合征（IBS）是一种常见的胃肠道疾病，其特征在于反复发作， 腹痛和排便障碍。IBS的确切机制知之甚少， 越来越多的证据表明，内脏痛觉过敏和心理社会应激发挥重要作用， 发病机制5-羟色胺（5-HT）在胃肠道中含量丰富，是胃肠道内主要的神经肽之一 参与IBS的发病机制。在啮齿类动物模型中，成年期持续的内脏痛觉过敏可以是 新生儿期应激源诱发，如新生儿母婴分离和直肠球囊扩张 膨胀我们以前曾报道过，早期生活压力源可以导致增强的反应， 肠神经系统的胆碱能通路。理论上内脏痛觉过敏和肠易激 综合征可通过逆转或抑制肾上腺素能途径的增强活性来治疗。 不幸的是，IBS的医学治疗一直令人失望。尽管一些5-HT受体调节剂 近年来，市场上销售的用于治疗IBS的药物中，存在对这些药物的安全性的关注。 另一方面，针灸已被广泛用于治疗各种疼痛状况， 中医胃肠道疾病根据中医理论， 肠易激综合征的常见病因是“肝气郁结攻脾， 脾的运化功能”。这是一种症状， 经常性腹痛、腹泻以及抑郁和焦虑等心理状况。基于 根据中医学的原理，正如《黄帝内经》中所提到的，最古老的中医药 书中说，应该“内用草药，外用针灸”。 我们以前的研究表明，电针（EA）产生长期的抗炎作用， 在完全弗氏佐剂（CFA）诱导的炎性痛觉过敏大鼠中的抗痛觉过敏作用。它 已经报道EA诱导的抗炎和抗痛觉过敏涉及功能的调节 在神经内分泌系统，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。 本研究旨在探讨电针对内脏痛敏的抑制作用及其机制 内脏痛觉过敏模型。我们假设，EA调节中枢处理和外周 在内脏伤害性通路中起信号传导作用，从而加重内脏痛觉过敏。具体 这项研究的目的是： 1.目的：观察电针对内脏痛模型大鼠行为反应和内脏反应的影响， 内脏痛觉过敏 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.观察电针对中缝背核和中缝核胆碱能活动的影响 内脏痛觉过敏大鼠中枢下行抑制通路的中继中枢magnus。