Project 2 - Mechanisms of Acupuncture's Effect on Inflammatory Pain

项目2——针灸治疗炎症性疼痛的机制

• 批准号: 7910397
• 负责人: BRIAN M BERMAN
• 金额: $ 33.96万
• 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
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7910397
• 关键词: Absence of pain sensation; Acupuncture Analgesia; Acupuncture procedure; Adrenal Cortex Hormones; Adrenal Glands; Adrenalectomy; Adverse effects; American; Animal Model; Anterior Pituitary Gland; Anti-Inflammatory Agents; Anti-inflammatory; Applications Grants; Arthritis; Arts; Attenuated; Bilateral; Biochemical; Blood - brain barrier anatomy; Chinese Herbs; Chinese Traditional Medicine; Chronic; Chronic inflammatory pain; Clinical Trials; Clinical Trials Design; Complement component C1s; Complementary and alternative medicine; Corticosterone; Corticotropin; Corticotropin-Releasing Hormone; Disease; Effectiveness; Electroacupuncture; Emotional; Freund' s Adjuvant; Grant; Herbal Medicine; Hormones; Hyperalgesia; Hypophysectomy; Hypothalamic structure; Inflammation; Inflammatory; Intervention; Knee Osteoarthritis; Laboratory Study; Laos; Leeches; Lidocaine; Measures; Mediating; Medical; Modality; Modeling; Neurobiology; Neuropeptides; Opioid; Pain; Pain management; Pan Genus; Pathogenesis; Patients; Peptides; Peripheral; Persistent pain; Pharmaceutical Preparations; Physiological; Pituitary Gland; Pituitary-Adrenal System; Plasma; Play; Principal Investigator; RU-486; Rattus; Reaction; Reporting; Risk; Role; Steroid Receptors; Stimulus; Symptoms; System; Technology; Testing; Therapeutic; Time; Traditional Medicine; addiction; astressin; cardiovascular risk factor; chronic pain; corticostatin; design; follow-up; gastrointestinal; inflammatory pain; injured; paraventricular nucleus; preclinical study; programs; research study

Millions of Americans suffer from moderate to severe persistent inflammatory pain, causing physical and emotional suffering. Non-steroidal anti-inflammatory drugs are commonly used for treating inflammatory pain. They are,however, associated with gastrointestinal disturbances and more recently cardiovascular risks. Opioids can be used to manage chronic pain, but their use is limited by adverse effects and the risk of addiction. It has been reported that about 50% of persistent pain sufferers lack effective pain control. Acupuncture, a therapeutic modality of traditional Chinese medicine (TCM), has been used for millenia to treat pain and a variety of other diseases and symptoms. 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, which mimics symptoms seen in patients with chronic inflammatory pain. This project is designed to define the underlying mechanisms of EA- produced anti-inflammation and anti-hyperalgesia. It has been well documented that the Hypothalamus- Pituitary-Adrenal axis (HPA)plays an important role in modulating inflammation and pain. EA'santi- inflammatory effect was attenuated in rats with adrenalectomy. Therefore, we hypothesize that EA activates the HPA axis to release corticosteroid (i.e.corticosterone in rats) that, at least in part, mediates the prolonged anti-inflammatory and anti-hyperalgesic effects. This hypothesis will be tested on the CFA-rat model. The specific aims are: Aim I: Determine ifEA regulates the plasma levels of HPA hormones in the rat model of peripheral inflammation and hyperalgesia. Following EAtreatment, the plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone in EA-treated and control rats will be measured and compared at various time points. Aim II: Characterize the role of the adrenal gland in EA-induced anti- inflammation and anti-hyperalgesia. The effects of EA will be evaluated in rats with bilateral adrenalectomy and those given a steroid receptor antagonist, RU486. Aim III:Characterize the role of the pituitary gland in EA-induced anti-inflammation and anti-hyperalgesia. The effects of EA will be evaluated in rats with hypophysectomy and those given an anti-ACTH-peptide, corticostatin-l. Aim IV: Characterize the role of the paraventricular nuclei (PVN) of hypothalamus in EA-induced anti-inflammation and anti-hyperalgesia. The effects of EA will be evaluated in rats with lidocaine-inactivated PVN and those given a corticotropin- releasing factor (CRF) antagonist, astressin. Along with other projects in the Center grant application, the findings will advance our understanding of the mechanisms of acupuncture and TCM and will provide valuable information for designing clinical trials for treating patients with chronic inflammatory pain.

数以百万计的美国人患有中度至重度持续性炎症疼痛，导致身体和 情感上的痛苦。非甾体类抗炎药通常用于治疗炎症 疼痛。然而，它们与胃肠道紊乱以及最近的心血管疾病有关。 风险。阿片类药物可用于治疗慢性疼痛，但其使用受到不良反应和风险的限制。 瘾。据报道，约50%的持续性疼痛患者缺乏有效的疼痛控制。 针灸是一种传统中医治疗方法，已有数千年的历史。 治疗疼痛和各种其他疾病和症状。先前的研究表明 电针（EA）对大鼠产生持久的抗炎和抗痛觉过敏作用 完全弗氏佐剂 (CFA) 诱导的炎症性痛觉过敏，类似于在 慢性炎症性疼痛患者。该项目旨在定义 EA 的底层机制 产生抗炎和抗痛觉过敏作用。有充分证据表明，下丘脑 - 垂体-肾上腺轴 (HPA) 在调节炎症和疼痛方面发挥着重要作用。 EA的反 肾上腺切除术的大鼠的炎症效应减弱。因此，我们假设 EA 激活 HPA 轴释放皮质类固醇（即大鼠中的皮质酮），至少部分介导 长效抗炎和抗痛觉过敏作用。该假设将在 CFA 大鼠上进行测试 模型。 具体目标是： 目标 I：确定 EA 是否调节大鼠模型中 HPA 激素的血浆水平 外周炎症和痛觉过敏。 EA 处理后，血浆水平 将测量经 EA 治疗的大鼠和对照大鼠的促肾上腺皮质激素 (ACTH) 和皮质酮，并 不同时间点进行比较。目标 II：表征肾上腺在 EA 诱导的抗- 炎症和抗痛觉过敏。将在双侧肾上腺切除的大鼠中评估 EA 的效果 以及那些给予类固醇受体拮抗剂 RU486 的患者。目标 III：描述脑下垂体在 EA 诱导的抗炎和抗痛觉过敏。将在大鼠中评估 EA 的效果 垂体切除术和给予抗 ACTH 肽、皮质抑素-l 的患者。目标 IV：描述 下丘脑室旁核（PVN）在电针诱导的抗炎和抗痛觉过敏中的作用。这 将在利多卡因灭活 PVN 的大鼠和给予促肾上腺皮质激素的大鼠中评估 EA 的效果 释放因子（CRF）拮抗剂，astressin。与中心拨款申请中的其他项目一起， 研究结果将增进我们对针灸和中医机制的理解，并将提供 为设计治疗慢性炎性疼痛患者的临床试验提供有价值的信息。