Effects of acupuncture on chemotherapy-induced pain

针灸对化疗引起的疼痛的影响

• 批准号: 7384803
• 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: 2008
• 资助国家: 美国
• 起止时间: 2008-02-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7384803
• 关键词: Acupuncture Points; Acupuncture procedure; Address; Affect; Aftercare; Agonist; Antineoplastic Agents; Bicuculline; Breast; Cancer Patient; Cancerous; Cells; Chinese People; Clinical Trials; Condition; Effectiveness; Electroacupuncture; GABA Receptor; Human; Hyperalgesia; Inflammatory; Injection of therapeutic agent; Interleukin-1; Interleukin-12; Interleukin-6; Investigation; Knowledge; Literature; Location; Lung Neoplasms; Maintenance; Mechanics; Mediating; Medical; Modality; Modeling; Nervous system structure; Neuroglia; Neurotransmitters; Nociception; Ovarian; Paclitaxel; Pain; Pain management; Patients; Peripheral Nervous System Diseases; Persistent pain; Posterior Horn Cells; Quality of life; Rattus; Spinal; Spinal Cord; Staging; Symptoms; TNF gene; Transcriptional Activation; Tumor Necrosis Factor-alpha; Up-Regulation; Week; Western Blotting; allodynia; base; cell type; chemotherapy; cytokine; day; dorsal horn; gamma-Aminobutyric Acid; neoplastic; nociceptive response; painful neuropathy; phaclofen; prevent; research study; success; transmission process; tumor

DESCRIPTION (provided by applicant): Chemotherapy-induced pain (CIP) is common in patients who receive anti-neoplastic agents. CIP is not yet adequately controlled, and it results in patient suffering, limits treatment with potentially useful anti-cancer drugs, and significantly affects the quality of life of cancer patients. Acupuncture, which has been used for millennia to treat pain, may alleviate CIP, but its effectiveness against this condition has not been studied and warrants investigation. Paclitaxel, an anti-neoplastic agent widely used to treat cancerous ovarian, breast and non-small cell lung tumors, produces neuropathic pain in humans and in rats. The objective of this study is to evaluate the effects and mechanisms of electroacupuncture (EA) on a paclitaxel-induced CIP rat model with persistent pain for 5 months. The hypothesis is that EA will alleviate the CIP at least in part by enhancing the activity of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, and consequently blocking pronociceptive cytokine expression in the spinal cord. The specific aims are: Aim 1: Evaluate EA's ability to inhibit CIP. After onset of allodynia on days 14-28 or before the paclitaxel injections and before onset of allodynia on days -2-12, EA treatment will be given at acupoint GB30 or ST30 every other day for two weeks to determine whether it alleviates and/or prevents CIP. We hypothesize that EA will relieve and prevent the CIP. Aim 2: Determine whether GABA affects EA alleviation of hyperalgesia/allodynia. The GABA receptor (A & B) antagonists bicuculline and phaclofen will be administered prior to EA treatment. We hypothesize that these antagonists will prevent EA-produced alleviation of CIP. Aim 3: Determine whether GABA affects EA inhibition of interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-1) and IL-6 in spinal cord. EA modulation of these cytokines, which are prototypical pro-inflammatory cytokines involved in pain maintenance, will be investigated in rats with and without GABA receptor antagonist pretreatment. Using western blot and immunostaining, we will examine IL-12, TNF-1 and IL-6 levels, the cell type that produces these cytokines, and the location of cytokine-immunoreactive cells in the spinal cord. We hypothesize that EA will significantly inhibit expression of these cytokines and that pretreatment with GABA receptor antagonists will block the EA effect. These studies will advance our knowledge of, and form the basis of a clinical trial of, the efficacy of EA in treating CIP. The success of the proposed study will greatly advance CIP management. Project Narrative: Chemotherapy-induced pain (CIP) occurs frequently in cancer patients who receive antineoplastic agents and, and has not been controlled adequately. Acupuncture has been used for millennia to treat pain. This study will evaluate the effects and mechanisms of electroacupuncture (EA) on such pain in a rat model. The success of the proposed study will greatly advance the management of CIP.

描述（由申请人提供）：化疗引起的疼痛（CIP）在接受抗肿瘤药物的患者中很常见。 CIP 尚未得到充分控制，它会导致患者痛苦，限制潜在有用的抗癌药物的治疗，并显着影响癌症患者的生活质量。针灸治疗疼痛已有数千年历史，可以缓解 CIP，但其针对这种情况的有效性尚未得到研究，值得进一步研究。紫杉醇是一种广泛用于治疗癌性卵巢癌、乳腺癌和非小细胞肺癌的抗肿瘤药物，可在人类和大鼠中产生神经性疼痛。本研究的目的是评估电针（EA）对紫杉醇诱导的持续疼痛5个月的CIP大鼠模型的作用和机制。假设认为，EA 至少可以部分通过增强主要抑制性神经递质 γ-氨基丁酸 (GABA) 的活性来缓解 CIP，从而阻断脊髓中促伤害细胞因子的表达。具体目标是： 目标 1：评估 EA 抑制 CIP 的能力。第14-28天异常性疼痛发作后或紫杉醇注射前和第-2-12天异常性疼痛发作前，每隔一天在GB30或ST30穴位进行电针治疗，持续两周，以确定是否减轻和/或防止 CIP。我们假设 EA 将缓解和预防 CIP。目标 2：确定 GABA 是否影响 EA 缓解痛觉过敏/异常性疼痛。 GABA 受体（A 和 B）拮抗剂荷包牡丹碱和法氯芬将在 EA 治疗前给药。我们假设这些拮抗剂将阻止 EA 产生的 CIP 缓解。目标 3：确定 GABA 是否影响脊髓中白细胞介素 12 (IL-12)、肿瘤坏死因子 α (TNF-1) 和 IL-6 的 EA 抑制。这些细胞因子是参与疼痛维持的典型促炎细胞因子，将在接受和不接受 GABA 受体拮抗剂预处理的大鼠中研究 EA 对这些细胞因子的调节。使用蛋白质印迹和免疫染色，我们将检查 IL-12、TNF-1 和 IL-6 水平、产生这些细胞因子的细胞类型以及细胞因子免疫反应细胞在脊髓中的位置。我们假设 EA 将显着抑制这些细胞因子的表达，并且用 GABA 受体拮抗剂进行预处理将阻断 EA 的作用。这些研究将增进我们对 EA 治疗 CIP 疗效的认识，并构成临床试验的基础。本研究的成功将极大地推进 CIP 管理。项目叙述：化疗引起的疼痛 (CIP) 经常发生在接受抗肿瘤药物治疗且未得到充分控制的癌症患者中。针灸治疗疼痛已有数千年历史。这项研究将在大鼠模型中评估电针（EA）对此类疼痛的影响和机制。本研究的成功将极大地推进 CIP 的管理。