Muscle Nociceptor Encoding of Noxious Mechanical Stimuli

有害机械刺激的肌肉伤害感受器编码

• 批准号: 6512227
• 负责人: Partap Singh Khalsa
• 金额: $ 7.53万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6512227
• 关键词: compression; laboratory rat; mechanical pressure; mechanoreceptors; muscle; nociceptors; pain; somatic afferent nerve; tendons

Muscle pain, due to mechanical causes, is pervasive in our lives. Acutely, it is initiated by mechanical stimulation, at tissue threatening (i.e., noxious) magnitudes, of specialized neurons innervating muscle called 'nociceptors'. The treatment of painful muscle conditions results in enormous expenditure of financial resources in the United States. Yet, our understanding of the underlying, peripheral, neural mechanisms that give rise to muscle pain due to mechanical causes if very limited. There are no quantitative biochemical studies of the neurophysiology of muscle or tendon nociceptors that encode noxious, mechanical stimuli. The relevant state of the mechanical stimulus at the level of the receptor has not been studied experimentally. Further, there are no robust mechanical models of how these sensory receptors are activated in situ. Hence, we are currently able to quantitatively predict the types of amounts of physical activity that will result in muscle pain in healthy individuals, much less those already injured or diseased. Nor can we predict the neurophysiological response to specific injuries. The aims of this research project will elucidate neural mechanisms that encode noxious, mechanical stimuli in muscle and that ultimately result in muscle pain. A first-order model will be developed to describe the activation of a nociceptor population in skeletal muscle. The 2 Specific Aims of this project are to determine 1) the relevant mechanical state that activates muscle and tendon nociceptors during stretch and passive compression; (2) how populations of muscle nociceptors encode noxious indentation. To accomplish these aims, the neural responses of single, nociceptors innervating tendon and muscle will be recording while simultaneously measuring the mechanical state that stimulates those neurons. The rat gracilis muscle will be used as a model system. Nociceptors innervating muscle or its tendons, do not experience the externally applied force or displacement during a noxious mechanical load. Rather, they experience the internally developed local stress (related to force) and/or local strain (related to displacement). In these experiments, the local stress and strain will be independently measured at the receptor endings of identified nociceptors. Nociceptors will be stimulated with noxious magnitudes of passive stretch and/or compression. A biomechanical model of single nociceptors and a nociceptor population response to noxious mechanical stimuli will be created.

由于机械原因引起的肌肉疼痛在我们的生活中普遍存在。急性地，它是由支配肌肉（称为“伤害感受器”）的特殊神经元以威胁组织（即有害）的机械刺激引发的。在美国，肌肉疼痛病症的治疗需要花费大量的财政资源。然而，我们对由于机械原因引起肌肉疼痛的潜在外周神经机制的理解非常有限。目前还没有对编码有害机械刺激的肌肉或肌腱伤害感受器的神经生理学进行定量生化研究。受体水平上机械刺激的相关状态尚未经过实验研究。此外，还没有关于这些感觉受体如何原位激活的可靠的机械模型。因此，我们目前能够定量预测会导致健康个体肌肉疼痛的体力活动量类型，更不用说那些已经受伤或患病的人了。我们也无法预测对特定损伤的神经生理反应。该研究项目的目的将阐明编码肌肉中有害机械刺激并最终导致肌肉疼痛的神经机制。将开发一阶模型来描述骨骼肌中伤害感受器群的激活。该项目的 2 个具体目标是确定 1）在拉伸和被动压缩过程中激活肌肉和肌腱伤害感受器的相关机械状态； (2) 肌肉伤害感受器群体如何编码有害压痕。为了实现这些目标，将记录支配肌腱和肌肉的单个伤害感受器的神经反应，同时测量刺激这些神经元的机械状态。大鼠股薄肌将用作模型系统。支配肌肉或其肌腱的伤害感受器在有害机械负载期间不会受到外部施加的力或位移。相反，它们会经历内部产生的局部应力（与力相关）和/或局部应变（与位移相关）。在这些实验中，将在已识别的伤害感受器的受体末端独立测量局部应力和应变。伤害感受器将受到有害程度的被动拉伸和/或压缩的刺激。将创建单个伤害感受器和伤害感受器群体对有害机械刺激的反应的生物力学模型。