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，肌肉疼痛在我们的生活中普遍存在。急性，它是通过机械刺激在威胁（即有害）幅度的机械刺激中引发的，该神经元神经肌肉称为“伤害感受器”。疼痛肌肉状况的治疗导致美国财务资源的巨大消费。然而，我们对基本，周围的神经机制的理解会导致机械原因引起的肌肉疼痛，如果非常有限。没有编码有害的机械刺激的肌肉或肌腱伤害感受器的神经生理学的定量生化研究。在受体水平上的机械刺激的相关状态尚未进行实验研究。此外，没有强大的机械模型，即这些感觉受体如何原位激活。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育活动量的类型，更不用说已经受伤或患病的人了。我们也不能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有害的，机械刺激的神经机制，并最终导致肌肉疼痛。将开发出一阶模型来描述骨骼肌中伤害感受器种群的激活。该项目的两个特定目的是确定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）肌肉伤害感受器的种群如何编码有害的凹痕。为了实现这些目的，单个伤害感受器的神经反应将记录肌腱和肌肉，同时测量刺激这些神经元的机械状态。大鼠Gracilis肌肉将用作模型系统。伤害肌肉或其肌腱支配，在有害的机械载荷期间不会经历外部施加的力或位移。相反，他们经历了内部发展的局部压力（与力）和/或局部菌株（与位移有关）。在这些实验中，局部应力和应变将在已识别的伤害感受器的受体末端独立测量。伤害感受器将被被动拉伸和/或压缩的有害幅度刺激。将创建单一伤害感受器的生物力学模型和对有害机械刺激的伤害感受器的反应。