Antinociceptive Mechanisms of Spinal Manipulative Therapy for Neuropathic Pain

脊柱手法治疗神经性疼痛的镇痛机制

• 批准号: 9377578
• 负责人: Stephen M. Onifer
• 金额: $ 45.15万
• 依托单位: PALMER COLLEGE OF CHIROPRACTIC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-05 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9377578
• 关键词: AM630; Absence of pain sensation; Academic Research Enhancement Awards; Acute Pain; Address; Agonist; Analgesics; Anesthesia procedures; Animal Model; Astrocytes; Behavior; Behavioral; Biomedical Research; Brain; CNR1 gene; CNR2 gene; Cannabinoids; Chronic; Chronic low back pain; Clinical; Custom; Data; Devices; Doctor of Chiropractic; Dose; Effectiveness; Endocannabinoids; Environment; Enzymes; Epidemic; Fifth lumbar vertebra; Goals; Hypersensitivity; Individual; Integrative Medicine; Interdisciplinary Study; Intervention; Isoflurane; Knowledge; Learning; Lumbar spinal cord structure; Measurement; Measures; Mechanics; Mediating; Mentors; Microglia; Mind-Body Intervention; Mission; Modeling; Molecular; Neuroglia; Neurons; Neuropathy; Neurotransmitters; Nociception; Opiate Addiction; Opioid; Osteopathic Medicine; Overdose; Pain; Pain in lower limb; Pain management; Periodicity; Peripheral; Peripheral Nervous System Diseases; Pharmacology; Physicians; Posterior Horn Cells; Postoperative Pain; Procedures; Rattus; Receptor Activation; Recruitment Activity; Research; Rodent; Site; Spinal; Spinal Manipulation; Spinal cord posterior horn; Stimulus; Students; System; Techniques; Testing; Traction; Translating; Vertebral column; addiction; adverse outcome; allodynia; ankle joint; base; cannabinoid receptor; cell type; chiropracty; chronic neuropathic pain; chronic pain; clinical efficacy; college; design; dorsal horn; endogenous cannabinoid system; evidence base; fatty acid amide hydrolase; improved; inhibitor/antagonist; innovation; interdisciplinary approach; interest; joint mobilization; mechanical allodynia; mouse model; multidisciplinary; multimodality; nerve injury; neurobiological mechanism; novel; painful neuropathy; physical therapist; prevent; receptor; socioeconomics; spared nerve; symptom management; transmission process

PROJECT SUMMARY Spinal manipulative therapy (SMT) is a non-pharmacologic, complementary and integrative health mind and body intervention that is widely used to treat chronic pain. However, the mechanism of analgesic action of SMT is not understood. Information is particularly sparse with respect to neuropathic pain, which exerts devastating personal and socioeconomic burdens. Pharmacological agents are the mainstay of symptoms management for neuropathic pain, but relief is weak and temporary, often associated with major adverse outcomes. For example, there is an epidemic of opiate addiction, abuse, and overdose. To begin to fill this knowledge gap, we have developed an innovative rat model of a frequently used non-thrust SMT technique, low velocity variable amplitude spinal manipulation (LVVA-SM). Our preliminary data in a well-characterized rat model of chronic peripheral neuropathic pain (spared nerve injury) indicate that LVVA-SM (10 min, 0.16Hz, 20° flexion, at the L5 vertebra) administered with our custom-made motorized device decreases behavioral signs of chronic pain (hindpaw mechanical allodynia). Our long-term goal is to determine the neurobiological mechanisms underlying this anti-allodynic effect of LVVA-SM. This R15 application proposes to leverage a multidisciplinary collaboration to characterize LVVA-SM-induced anti-allodynia (Aim 1) and then to determine whether this is mediated by endogenous activation of cannabinoid receptors in the spinal cord dorsal horn (Aim 2), an important site of nociceptive transmission. The project is directly relevant to the chiropractic profession's interest in taking an evidence-based approach to treating chronic pain and strengthening Palmer College of Chiropractic's research environment. The goals of the R15 program are strongly aligned with Palmer's research mission, namely to conduct meritorious research on SMT and provide an opportunity for students to learn about biomedical research through mentored hands-on participation. If successful, this project will provide clinicians with potentially translatable data that will improve the rationale for and the efficacy of SMT.

项目概要 脊柱手法治疗（SMT）是一种非药物性、补充性、综合性的身心健康疗法 广泛用于治疗慢性疼痛的身体干预然而，SMT的镇痛作用机制。 关于神经性疼痛的信息尤其匮乏，这种疼痛具有毁灭性。 个人和社会经济负担。药物是症状管理的支柱。 神经性疼痛，但缓解效果较弱且短暂，通常与严重不良后果相关。 例如，鸦片成瘾、滥用和过量流行，为了开始填补这一知识空白。 开发了一种创新的大鼠模型，该模型采用常用的非推力 SMT 技术、低速变量 我们在慢性大鼠模型中得到的初步数据。 周围神经性疼痛（神经损伤）表明 LVVA-SM（10 分钟，0.16Hz，20° 屈曲，在 L5 使用我们定制的机动装置进行管理可减少慢性疼痛的行为症状 （后爪机械异常性疼痛）。我们的长期目标是确定神经生物学机制。 LVVA-SM 的抗异常疼痛作用的基础是该 R15 应用建议利用多学科。 合作来表征 LVVA-SM 诱导的抗异常性疼痛（目标 1），然后确定这是否是 由脊髓背角大麻素受体的内源性激活介导（目标 2）， 该项目与脊椎按摩治疗行业直接相关。 有兴趣采取循证方法来治疗慢性疼痛并加强帕尔默学院的实力 R15 计划的目标与 Palmer 的研究环境高度一致。 研究任务，即对 SMT 进行有价值的研究，并为学生提供机会 通过指导实践参与了解生物医学研究如果成功，该项目将。 为前沿提供潜在的可翻译数据，这将提高 SMT 的基本原理和效率。