Effects of acupuncture on pain-induced affective response

针灸对疼痛引起的情感反应的影响

• 批准号: 7773357
• 负责人: RUIXIN ZHANG
• 金额: $ 22.5万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7773357
• 关键词: Acupuncture Points; Acupuncture procedure; Adverse effects; Affective; Animal Model; Anterior; Behavior; CTOP; Clinical Trials; Dimensions; Disease; Electroacupuncture; Emotional; Formalin; Freund' s Adjuvant; Hydrochloride Salt; Hyperalgesia; Inflammation; Injection of therapeutic agent; Knowledge; Mechanical Stimulation; Mediating; Mental disorders; Microinjections; Modality; Modeling; Morphine; N-Methyl-D-Aspartate Receptors; NR1 gene; Naloxone; Nerve; Opioid; Opioid Receptor; Pain; Pain management; Patients; Peripheral; Persistent pain; Pharmaceutical Preparations; Phosphorylation; Process; Rat-1; Rattus; Reporting; Sensory; Staging; Testing; Therapeutic; Western Blotting; cingulate cortex; cysteinyltyrosine; endogenous opioids; experience; injured; kappa opioid receptors; mu opioid receptors; naltrindole; norbinaltorphimine; prevent; public health relevance; receptor function; research study; response; success

DESCRIPTION (provided by applicant): Pain experience has both sensory and affective dimensions. Current drugs for pain and pain-induced negative psychological disorders have limited efficacy and unwanted side effects. An ideal therapeutic modality should treat sensory and affective pain simultaneously with few side effects. Studies have demonstrated that electroacupuncture (EA), which has few or no adverse effects, significantly inhibits hyperalgesia, the sensory discriminative dimension of pain, but its effects on the affective dimension have not been tested. Previous studies show that opioids and NMDA receptors in the anterior cingulate cortex (ACC) are involved in affective responses. The objective of this study is to evaluate the effects and mechanisms of EA on pain-induced affective behavior. The hypothesis is that EA inhibits affective response by activating endogenous opioids and inhibiting NR1 phosphorylation in the ACC. We will use an animal model of peripheral CFA (complete Freund adjuvant)-induced affective response, assessed with a conditioned place avoidance (CPA) test, recently established in our lab to mimic the emotional responses of patients with pain. The aims are: Aim I: Evaluate the effects of EA on pain-induced affective response. EA at 10 or 100 Hz, 20 min and 3 mA, the maximum current intensity tolerated by rats, will be used at acupoint GB30 (Huan Tiao) to study how EA influences a rat model of affective response. We hypothesize that EA will significantly inhibit this response. Aim II: Determine whether opioids mediate EA inhibition of affective response. The involvement of opioids in EA action will be determined by administering selective mu, delta and kappa opioid receptor antagonists to the ACC. We hypothesize that these antagonists will prevent EA inhibition of affective response. Aim III: Determine whether EA inhibits phosphorylation of NR1, the essential subunit of NMDA receptor, and its modulation by opioids in the ACC. Rats with and without opioid receptor antagonist pretreatment will be treated with EA. We will examine NR1 phosphorylation levels using western blot. We hypothesize that EA will significantly inhibit NR1 phosphorylation, and that opioid receptor antagonist pretreatment will block this effect. The findings of this study will advance our understanding of the influence of EA treatment on the affective dimension of pain. The success of the study will provide important information for a clinical trial on the affective dimension of pain and has the potential of greatly advancing pain management. PUBLIC HEALTH RELEVANCE: Pain procession is consisted of sensory and affective dimensions. Inadequate control and management of pain remain serious problems. Previous studies have demonstrated that electroacupuncture (EA) significantly inhibits hyperalgesia, the sensory dimension. Whether EA modulate the affective dimension has not been investigated. This study will evaluate the effects and mechanisms of EA on affective dimension. The findings will advance our knowledge of EA treatment on affective dimensions of pain. The success of this study will provide important information for a clinical trial and finally greatly advance the management of pain.

描述（由申请人提供）：疼痛体验有感官和情感两个维度。目前治疗疼痛和疼痛引起的消极心理障碍的药物疗效有限，并且有不良副作用。理想的治疗方式应该同时治疗感觉疼痛和情感疼痛，并且副作用很少。研究表明，电针（EA）几乎没有或没有副作用，可以显着抑制痛觉过敏（疼痛的感觉辨别维度），但其对情感维度的影响尚未得到测试。先前的研究表明，前扣带皮层 (ACC) 中的阿片类药物和 NMDA 受体参与情感反应。本研究的目的是评估电针对疼痛引起的情感行为的影响和机制。假设认为 EA 通过激活内源性阿片类药物并抑制 ACC 中的 NR1 磷酸化来抑制情感反应。我们将使用外周 CFA（完全弗氏佐剂）诱导的情感反应动物模型，并通过条件性位置回避 (CPA) 测试进行评估，该测试是我们实验室最近建立的，用于模拟疼痛患者的情绪反应。目标是： 目标 I：评估 EA 对疼痛引起的情感反应的影响。将在 10 或 100 Hz、20 分钟和 3 mA（大鼠可耐受的最大电流强度）下对 GB30 穴位（还条）进行 EA，以研究 EA 如何影响大鼠模型的情感反应。我们假设 EA 将显着抑制这种反应。目标 II：确定阿片类药物是否介导 EA 对情感反应的抑制。阿片类药物在 EA 作用中的参与将通过向 ACC 施用选择性 mu、δ 和 kappa 阿片类受体拮抗剂来确定。我们假设这些拮抗剂将阻止 EA 对情感反应的抑制。目标 III：确定 EA 是否抑制 NR1（NMDA 受体的重要亚基）的磷酸化及其 ACC 中阿片类药物的调节。接受或不接受阿片受体拮抗剂预处理的大鼠均将接受 EA 治疗。我们将使用蛋白质印迹检查 NR1 磷酸化水平。我们假设 EA 将显着抑制 NR1 磷酸化，而阿片受体拮抗剂预处理将阻断这种作用。这项研究的结果将加深我们对电针治疗对疼痛情感维度影响的理解。该研究的成功将为疼痛情感维度的临床试验提供重要信息，并有可能极大地推进疼痛管理。 公共卫生相关性：疼痛过程由感觉和情感维度组成。对疼痛的控制和管理不足仍然是严重的问题。先前的研究表明，电针（EA）可显着抑制痛觉过敏（感觉维度）。 EA 是否调节情感维度尚未被研究。本研究将评估 EA 对情感维度的影响和机制。这些发现将增进我们对电针治疗疼痛情感维度的了解。这项研究的成功将为临床试验提供重要信息，并最终极大地推进疼痛的管理。