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)疗法已被证明对慢性肌肉骨骼疼痛的治疗是有益的。手动和运动疗法的一个重要组成部分是软组织(肌肉和结缔组织)的拉伸。最近的一项人体超声研究表明，结缔组织可能在慢性下腰痛的发病机制中发挥了作用。重要的是，人们对腰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。该项目的总体目标是检验组织拉伸可降低局部结缔组织炎症引起的机械敏感性、细胞因子产生和神经肽产生的假说。本项目的具体目的是量化大鼠下背部结缔组织发出的感觉神经纤维的神经肽表达(目标1)，建立大鼠下背部结缔组织炎症模型(目标2a)，并比较体内组织拉伸和不拉伸在结缔组织炎症模型中的作用(目标2b)。为了量化感觉神经纤维的表达，我们将使用逆行示踪法来识别从背部下部投射出来的细胞 大鼠，用免疫组织化学方法鉴定感觉神经细胞。所有从腰部突出的细胞都将被计数，进一步的分析将包括计算这些细胞的亚群，这些细胞也表达感觉神经肽。为了评价组织拉伸对结缔组织炎症的影响，我们将一种活体动物拉伸的方法应用于大鼠结缔组织炎症模型。这种炎症模型以及拉伸可能导致的后续变化将通过以下方法进行评估：机械敏感度变化的行为学测试、测量细胞因子表达变化的促炎细胞因子阵列、评估组织炎症的组织学、评估组织中神经肽释放的酶免疫分析和评估背根神经节神经肽表达的免疫组织化学。 与公共卫生相关：包括腰痛在内的慢性肌肉骨骼疼痛每年影响数百万人。拉伸结缔组织和肌肉是以身体为基础的(手动和运动)疗法和传统物理疗法的基本组成部分，这两种疗法都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，治疗可以定制为对患者产生最大好处。

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.