Inflammation model of body-based treatment for chronic musculoskeletal pain

描述（由申请人提供）：基于身体的（手动和运动）疗法已被证明有利于治疗慢性肌肉骨骼疼痛。基于手动和运动的治疗的一个重要组成部分是伸展软组织（肌肉和结缔组织）。最近的一项人体超声研究表明，结缔组织可能在慢性腰痛的发病机制中发挥作用。重要的是，我们对下背部结缔组织的神经支配以及这些组织对炎症的反应知之甚少。本项目的总体目标是检验组织拉伸减弱局部结缔组织炎症诱导的机械敏感性、细胞因子产生和神经肽产生的假设。本项目的具体目的是量化从大鼠下背部结缔组织投射的感觉神经纤维的神经肽表达（目的1），建立大鼠下背部结缔组织炎症模型（目的2a），并比较体内组织拉伸与无拉伸在结缔组织炎症模型中的作用（目的2b）。为了量化感觉神经纤维的表达，我们将使用逆行示踪方法来识别从下背部投射的细胞， 免疫组化法鉴定感觉神经细胞。将对从下背部突出的所有细胞进行计数，并且进一步分析将涉及对也表达感觉神经肽的这些细胞的亚群进行计数。为了评估组织拉伸对结缔组织炎症的影响，我们将在体内动物拉伸的方法应用于大鼠结缔组织炎症模型。该炎症模型和可能由拉伸诱导的后续变化将通过以下方法进行评价：机械敏感性变化的行为测试、测量细胞因子表达变化的促炎细胞因子阵列、评价组织炎症的组织学、评价组织中神经肽释放的酶免疫测定和评价背根神经节中神经肽表达的免疫组织化学。 公共卫生相关性：包括腰痛在内的慢性肌肉骨骼疼痛每年影响数百万人。结缔组织和肌肉的拉伸是基于身体的（手动和运动）疗法和传统物理疗法的基本组成部分，这两种疗法通常用于治疗持续性和慢性肌肉骨骼疼痛。基于身体的治疗是非侵入性的，如果能够阐明减轻疼痛和炎症的外周机制，则可以定制治疗以使患者获得最大益处。

DESCRIPTION (provided by applicant): Body-based (manual and movement) therapies have been shown to be beneficial for the treatment of chronic musculoskeletal pain. An important component of manual and movement based therapies is stretching of soft tissues (muscle and connective tissue). A recent ultrasound study in humans suggests that connective tissue may play a role in the pathogenesis of chronic low back pain. Importantly very little is known about the innervation of connective tissues in the low back or how these tissues respond to inflammation. The overall objective of this project is to test the hypothesis that tissue stretch attenuates mechanical sensitivity, cytokine production and neuropeptide production induced by local connective tissue inflammation. The specific Aims of this project are to quantify the neuropeptide expression of sensory nerve fibers projecting from the connective tissues of the low back in the rat (Aim 1), to develop a model of connective tissue inflammation in the low back of the rat (Aim 2a) and to compare the effect of in vivo tissue stretch vs. no stretch in the model of connective tissue inflammation (Aim 2b). To quantify sensory nerve fiber expression we will use retrograde tracer methods to identify the cells that project from the low back in the rat, and immunohlstochemical methods to identify the sensory nerve cells. All cells that project from the low back will be counted and further analysis will involve counting the subpopulation of these cells that also express sensory neuropeptides. To evaluate the effect of tissue stretch on connective tissue inflammation we will apply a method of in vivo animal stretch to a model of connective tissue inflammation in the rat. This inflammatory model and the subsequent changes that may be induced by stretch will be evaluated with behavioral tests for changes in mechanical sensitivity, a pro-inflammatory cytokine array to measure changes in cytokine expression, histology to evaluate inflammation in tissue, enzyme immunoassay to evaluate neuropeptide release in tissue and immunohistochemistry to evaluate neuropeptide expression in dorsal root ganglia. PUBLIC HEALTH RELEVANCE: Chronic musculoskeletal pain including low back pain affects millions of people every year. Stretching of connective tissue and muscle is a fundamental component of body-based (manual and movement) therapies and conventional physical therapy both of which are commonly used to treat persistent and chronic musculoskeletal pain. Body-based therapies are non-invasive and if the peripheral mechanism conferring a decrease in pain and inflammation can be elucidated, treatments could be tailored to effect maximal benefit to the patient.