Endogenous Mechanisms of Electroacupuncture

电针的内源性机制

• 批准号: 8528481
• 负责人: Carolyn A Fairbanks
• 金额: $ 18.31万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8528481
• 关键词: Absence of pain sensation; Acupuncture Analgesia; Acupuncture procedure; Address; Adopted; Affinity; Agmatine; Analgesics; Area; Arginine; China; Complement; Consensus; Data; Dependence; Development; Drug Addiction; Effectiveness; Electroacupuncture; Endorphins; Genetic; Glutamates; Goals; Hypersensitivity; Immunoglobulin G; Inflammatory; Intrathecal Injections; Japan; Knowledge; Learning; Long-Term Effects; Mediating; Memory; Microdialysis; Molecular; N-Methyl-D-Aspartate Receptors; N-Methylaspartate; Nerve; Neuraxis; Neuronal Plasticity; Neurotransmitters; Nitric Oxide Synthase; North America; Opioid; Outcome; Pain; Pain management; Pharmacological Treatment; Pharmacotherapy; Physiological; Play; Positioning Attribute; Publishing; Regulation; Research; Rodent Model; Role; Site; Spinal; Spinal Cord; Spinal cord posterior horn; Synaptic Vesicles; System; Techniques; Testing; Therapeutic; Translating; United States; United States National Institutes of Health; Work; addiction; allodynia; base; chronic pain; chronic stroke; effective therapy; expectation; improved; in vivo; inhibitor/antagonist; innovation; mechanical allodynia; nerve injury; neuroadaptation; novel; novel therapeutic intervention; preclinical study; prevent; programs; receptor; relating to nervous system

DESCRIPTION (provided by applicant): Acupuncture and electroacupuncture have been increasingly adopted in North America as a complement to pharmacotherapy for chronic pain over the last twenty years (1997 NIH Consensus Statement on Acupuncture). At least thirty years of research indicate a role for opioidergic systems in the mechanisms underlying acupuncture-evoked analgesia. However, the mechanism(s) underlying the effectiveness of acupuncture for pain management remains only partially understood. In recent years a role for NMDA receptor antagonists to enhance opioid analgesia by inhibition of the development of analgesic tolerance has been clearly defined. However, the contribution of endogenous modulators of the NMDA receptor system to analgesia induced by acupuncture has been minimally explored. Agmatine (decarboxylated arginine) is an endogenous substance that antagonizes the NMDA receptor and inhibits nitric oxide synthase. Like synthetic NMDA receptor antagonists, agmatine also inhibits development of opioid tolerance and dependence. Since agmatine is expressed in the CNS, strategies could be used to optimize its activity in CNS regions where electroacupuncture exerts therapeutic benefit. The objective of this application is to determine the mechanism by which agmatine contributes to electroacupuncture-evoked analgesia. The central hypothesis is that endogenous agmatine exerts its effects through inhibition of the NMDA receptor at the NR2B receptor subunit. The rationale for the proposed research is that, with demonstration of endogenous agmatine participation in electroacupuncture-evoked analgesia and identification of the mechanism, endogenous agmatine could be regulated in site-specifically to optimize electroacupuncture therapy. Two specific aims are proposed: #1: Determine the extent to which and the mechanism by which endogenous agmatine contributes to electroacupuncture-induced pain control. #2: Determine the ability of electroacupuncture to release endogenous agmatine. This contribution will be significant because understanding how agmatine manifests its effects is an important step toward optimizing its therapeutic application in both non-pharmacological and pharmacological pain management approaches. The research proposed in this application is innovative because it represents a new mechanism to explain analgesia evoked by electroacupuncture, a commonly applied non-pharmacological pain management therapy that is not well understood. The successful completion of this research is expected to position both electroacupuncture and agmatine as complementary approaches to improve pain management and therapy that may translate to other therapeutic indications arising from maladaptive neuroplasticity.

描述（由申请人提供）：北美越来越多地采用针灸和电针，作为对过去二十年（1997年NIH关于针灸的共识声明）的药物治疗的补充。至少三十年的研究表明阿片类系统在针灸诱发的镇痛的基础机制中的作用。但是，针灸对疼痛管理的有效性的基础机制仍然仅部分理解。近年来，已经明确定义了NMDA受体拮抗剂通过抑制镇痛耐受性发展来增强阿片类镇痛的作用。然而，已经最少探索了NMDA受体系统的内源调节因子对由针灸诱导的镇痛的贡献。琼脂氨酸（脱羧精氨酸）是一种内源性物质，可拮抗NMDA受体并抑制一氧化氮合酶。像合成的NMDA受体拮抗剂一样，琼脂氨酸也抑制阿片类药物耐受性和依赖性的发展。由于Agmatine在中枢神经系统中表达，因此可以使用策略来优化其在CNS区域的活动，而CNS区域具有具有治疗益处的CNS区域。该应用的目的是确定琼脂氨酸对电针诱发的镇痛作用的机制。中心假设是，内源性邻玛汀通过在NR2B受体亚基上抑制NMDA受体来发挥其作用。拟议的研究的理由是，通过表明内源性琼脂碱参与电针诱发的镇痛和机制的鉴定，内源性agmatine可以在特定于特定于特定于现场的调节，以优化电针治疗。提出了两个具体的目标：＃1：确定内源性邻玛汀在多大程度上以及在多大程度上有助于电针诱导的疼痛控制。 ＃2：确定电针的能力释放内源性邻玛汀。这项贡献将是重要的，因为了解琼脂氨酸如何表现其影响是优化其在非药物和药理疼痛管理方法中的治疗应用的重要步骤。该应用中提出的研究具有创新性，因为它代表了一种新的机制来解释由电针仪引起的镇痛，这是一种常用的非药物疼痛管理疗法，尚未得到充分理解。预计这项研究的成功完成将定位电针和琼脂碱作为改善疼痛管理和治疗方法的补充方法，这可能转化为因不良适应性神经可塑性引起的其他治疗迹象。