Acute-to-Chronic Transition in Ergonomic Muscle Pain: Nociceptor Mechanisms

符合人体工程学的肌肉疼痛从急性到慢性的转变：伤害感受器机制

• 批准号: 10338064
• 负责人: JON DAVID LEVINE
• 金额: $ 61.69万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-05 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10338064
• 关键词: Absence of pain sensation; Acute; Adult; Affect; Age; Anti-Inflammatory Agents; Attenuated; Autoimmune; Chronic; Clinical; Cutaneous; Development; Diagnosis; Drops; Economic Burden; Economics; Elements; Endocrine; Event; Exposure to; Failure; Financial compensation; Foundations; Functional disorder; Goals; Health; Immune; Inflammatory; Injury; Interleukin-10; Intervention; Knowledge; Life; Medical; Molecular; Muscle; Musculoskeletal Pain; Myalgia; Myopathy; Natural regeneration; Neuropathy; Nociception; Nociceptors; Outcome; Pain; Pain Research; Pain Threshold; Patients; Peripheral; Persistent pain; Persons; Phenotype; Physical activity; Physiological Adaptation; Population; Pre-Clinical Model; Productivity; Psychological Factors; Psychological Stress; Quality of life; Recovery; Regenerative capacity; Regenerative response; Research; Resistance; Role; Scanning; Signal Pathway; Site; Sodium Channel; Stimulus; Strenuous Exercise; Stress; Syndrome; Therapeutic Intervention; Time; Tissues; Translating; Voltage-Gated Potassium Channel; Woman; Work; adaptive immune response; base; biological adaptation to stress; chronic musculoskeletal pain; chronic pain; cytokine; effective therapy; hypothalamic-pituitary-adrenal axis; macrophage; novel strategies; pain inhibition; payment; physically handicapped; prevent; programs; psychologic; recruit; relating to nervous system; repaired; resilience; response; sensor; sex; side effect; voltage

Abstract Chronic musculoskeletal pain is a very common and frequently disabling condition that affects up to 50% of the adult population worldwide, having a huge impact on quality of life and economic burden, loses related to medical expenses, lower labor productivity and increased compensation claims. Unfortunately, our lack of understanding of the mechanisms underlying this condition has precluded the development of rationale, safe and effective therapies. While some people display resilience to chronic musculoskeletal pain, research has only focused on the psychological aspects involved in such resilience. However, growing evidence suggests that, in addition to psychological factors, a physical component is critical to achieve resilience to chronic pain and that failure to display adequate reparative and/or regenerative responses is associated with persistent pain. The phenomenon of repeated bout effect (RBE) is a common and natural example of the involvement of an endogenous reparative response (i.e., physical resilience) to muscle injury and persistent pain. Initial exposure to strenuous muscle activity produces significant pain, loss of force and tissue damage, which over time resolves without any external intervention. Re-exposure to the same activity, will however, produce much less pain, dysfunction and tissue damage, suggesting that physical resilience is enhanced by the muscle activity. Although recent research has underlined the importance of immune, endocrine and neural responses in muscle repair and regeneration, whether they also contribute to recovery from persistent musculoskeletal pain is unknown. Furthermore, whether exposure to stress or repetitive ergonomic tasks interferes with physical resilience, leading to chronic musculoskeletal pain, remains unknown. We plan to combine our expertise in several experimental approaches and our new preclinical model of RBE to study physical resilience, to achieve the three major goals of this proposal: (1) elucidate the role of muscle activity in physical resilience, with emphasis on mechanisms of ergonomic injury-induced chronic muscle pain; (2) evaluate the interaction between stress and physical resilience on chronic musculoskeletal pain, especially in regard to the role of early-life interventions on physical resilience and muscle nociceptor hyperexcitability; and, (3) assess the effect of physical resilience on neuropathic muscle pain, with emphasis on cellular and molecular mechanisms of muscle nociceptor dysfunction. !

摘要 慢性肌肉骨骼疼痛是一种非常常见且经常致残的疾病，影响多达50%的 世界各地的成年人口对生活质量和经济负担产生了巨大的影响，失去了与 医疗费用，较低的劳动生产率和增加的赔偿要求。不幸的是，我们缺乏 对这种情况背后的机制的理解阻碍了SAFE的理论基础的发展 以及有效的治疗方法。虽然有些人对慢性肌肉骨骼疼痛表现出韧性，但研究发现 只关注这种韧性所涉及的心理方面。然而，越来越多的证据表明 除了心理因素外，身体因素对获得对慢性疼痛的弹性至关重要 而不能显示足够的修复性和/或再生反应与持续性 疼痛。重复回合效应(RBE)现象是一个常见的、自然的例子 对肌肉损伤和持续性疼痛的内源性修复反应(即身体弹性)。首字母 暴露在剧烈的肌肉活动中会产生显著的疼痛、力量丧失和组织损伤， 时间在没有任何外部干预的情况下解决。然而，重新接触同样的活动会产生很大的影响 较少的疼痛、功能障碍和组织损伤，表明肌肉增强了身体的弹性 活动。尽管最近的研究强调了免疫、内分泌和神经反应的重要性 在肌肉修复和再生方面，它们是否也有助于从持续性肌肉骨骼中恢复 疼痛是未知的。此外，无论是暴露在压力下还是重复的人体工程学任务都会干扰 导致慢性肌肉骨骼疼痛的身体弹性仍然未知。我们计划将我们的 几种实验方法的专业知识和我们用于研究物理的RBE新的临床前模型 复原力，以实现本提案的三个主要目标：(1)阐明肌肉活动在身体活动中的作用 恢复力，强调人体工学损伤导致慢性肌肉疼痛的机制；(2)评估 慢性肌肉骨骼疼痛的应激和身体弹性之间的相互作用，特别是关于 早期生活干预对身体复原力和肌肉伤害性感受器过度兴奋的作用；以及，(3)评估 身体弹性对神经病理性肌肉疼痛的影响，重点是细胞和分子方面的影响 肌肉伤害性感受器功能障碍的机制。 好了！

项目成果

Screening the role of pronociceptive molecules in a rodent model of endometriosis pain.

• DOI: 10.1016/j.jpain.2014.04.002
• 发表时间: 2014-07
• 期刊: JOURNAL OF PAIN
• 影响因子: 4
• 作者: Alvarez, Pedro;Levine, Jon D.
• 通讯作者: Levine, Jon D.

Ectopic endometrium-derived leptin produces estrogen-dependent chronic pain in a rat model of endometriosis.

• DOI: 10.1016/j.neuroscience.2013.11.008
• 发表时间: 2014-01-31
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Alvarez P;Bogen O;Chen X;Giudice LC;Levine JD
• 通讯作者: Levine JD

Impact of surgical excision of lesions on pain in a rat model of endometriosis.

• DOI: 10.1002/ejp.527
• 发表时间: 2015-01
• 期刊: EUROPEAN JOURNAL OF PAIN
• 影响因子: 3.6
• 作者: Alvarez, P.;Giudice, L. C.;Levine, J. D.
• 通讯作者: Levine, J. D.

Generation of a pain memory in the primary afferent nociceptor triggered by PKCε activation of CPEB.

• DOI: 10.1523/jneurosci.5138-11.2012
• 发表时间: 2012-02-08
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Bogen O;Alessandri-Haber N;Chu C;Gear RW;Levine JD
• 通讯作者: Levine JD

In vivo and in vitro comparison of female and male nociceptors.

体内和男性伤害感受器的体外比较。

• DOI: 10.1016/j.jpain.2012.09.009
• 发表时间: 2012-12
• 期刊: JOURNAL OF PAIN
• 影响因子: 4
• 作者: Hendrich, Jan;Alvarez, Pedro;Joseph, Elizabeth K.;Ferrari, Luiz F.;Chen, Xiaojie;Levine, Jon D.
• 通讯作者: Levine, Jon D.