Proprioceptive mechanisms underlying post-spinal manipulation response in an NGF-induced low back pain model

抽象的。 腰痛(LBP)是美国的一个主要健康问题，每年造成超过500亿美元的治疗相关成本和1000亿美元的间接成本(即生产力损失)。最近过度依赖处方阿片类药物来治疗疼痛，进一步加剧了这场国家健康危机。高速低幅脊柱手法(HVLA-SM)是大多数临床实践指南推荐的一种非药物性LBP方法。然而，缺乏关于潜在神经生理机制的知识阻碍了这种治疗方法的更广泛的临床接受、使用和优化。已提出的HVLA-SM疗效机制包括与快速拉伸刺激肌肉和/或其他躯干组织中的机械感受器相关的肌梭敏感性的改变。我们实验室以前的工作已经阐明了在非化学敏感环境中，HVLA-SM的机械特性(推力持续时间、推力幅度、推力速率、预载荷大小和持续时间以及推力接触位置)与躯干肌梭传入反应之间的关系。最近，使用商业上可获得的极短推力持续时间为2-3ms的HVLA-SM装置进行的初步研究显示，在HVLA-SM恢复到基线肌梭放电之间存在二分性。不同的纺锤体传入亚群在HVLA-SM后相对较快地恢复到基线放电(&lt；2s)，而其他亚群需要相当长的时间(&gt；10s)，这远远超过HVLA-SM的机械刺激。导致HVLA-SM后反应二分性的生物学和/或生物力学因素，以及临床上相关的组织化学增敏是否能最大化这些HVLA-SM后的二分性反应，目前尚不清楚。最近开发的临床前LBP模型已经使用翻译相关的疼痛分子神经生长因子(NGF)建立。NGF是一种与疼痛相关的神经营养因子，在肌肉损伤、炎症和/或周围神经损伤后自然上调。将神经生长因子注射到深部躯干肌肉系统，通过敏化骨骼肌伤害性感受器和产生明显的脊髓背角神经元超兴奋性，产生持续性(数天/数周)的局部躯干痛敏；这两者被认为是LBP慢性化的关键组成部分。这项建议将基于融合内纤维分类、HVLA-SM推力持续时间(2-3ms对100ms)以及在对照和躯干化学敏感(NGF诱导的LBP)环境中达到的深层脊柱组织(多裂肌)的HVLA-SM峰值生物力学力来表征HVLA-SM肌梭反应，以揭示脊柱操作的神经生理学机制，并建立另一种临床前NGF诱导的LBP模型，以便更好地了解和/或优化这种非药物治疗LBP的方法。

Abstract. Low back pain (LBP) is a major health problem in the United States costing annually over $50 billion in treatment-related costs and $100 billion in indirect costs (i.e. lost productivity). This national health crisis is further compounded by a recent over-reliance on prescription opioids for therapeutic pain management. High velocity low amplitude spinal manipulation (HVLA-SM) is a non-pharmacological LBP approach recommended by a majority of clinical practice guidelines. However, a lack of knowledge concerning underlying neurophysiological mechanisms hinders wider clinical acceptance, usage, and optimization of this therapeutic approach. Proposed mechanisms of HVLA-SM efficacy include changes in muscle spindle sensitivity related to rapid stretch-induced stimulation of mechanoreceptors in muscle and/or other trunk tissues. Previous work in our lab has shed light on the relationship between the mechanical characteristics of HVLA-SM (thrust duration, thrust amplitude, thrust rate, preload magnitude & duration, and thrust contact site) and trunk muscle spindle afferent responsiveness in non-chemosensitized environments. Recently pilot studies using commercially available HVLA-SM devices with extremely short thrust durations of 2-3ms revealed a dichotomy among post-HVLA-SM return to baseline muscle spindle discharge. Distinct subpopulations of spindle afferents returned to baseline discharge post-HVLA-SM relatively rapidly (<2s), while others required substantially longer periods (>10s), which far outlasted the mechanical stimulus of HVLA-SM. The biological and/or biomechanical factors responsible for this post-HVLA-SM response dichotomy, as well as whether or not clinically relevant tissue chemosensitization acts to maximize these dichotomous post-HVLA-SM responses is currently unknown. A recently developed preclinical LBP model has been established using a translationally relevant pain molecule, nerve growth factor (NGF). NGF is a neurotrophin associated with pain which is naturally upregulated after muscle damage, inflammation, and/or peripheral nerve injury. Injection of NGF into deep trunk musculature creates persistent (days/weeks), localized trunk hyperalgesia by sensitizing skeletal muscle nociceptors and producing marked spinal dorsal horn neuron hyperexcitability; both of which are thought to be key components of LBP chronicity. This proposal will characterize post-HVLA-SM muscle spindle response based on intrafusal fiber classification, HVLA-SM thrust duration (2-3ms vs 100ms), and HVLA-SM peak biomechanical forces reaching deep spinal tissues (multifidus muscle) in control and trunk chemosensitized (NGF-induced LBP) environments in order to reveal neurophysiological mechanisms underlying spinal manipulation and to establish another preclinical NGF-induced LBP model so as to better inform and/or optimize this non-pharmacological approach to LBP.