OSTEOARTHRITIS AND KNEE JOINT PAIN

描述(由申请人提供)： 摘要：骨性关节炎症状是患者求医的主要原因，但目前尚无有效的方法来缓解骨性关节炎引起的疼痛。我们的长期目标是通过研究实验性骨性关节炎模型中的神经解剖学方法，并在人类关节组织中进行验证，来了解软骨退变程度与关节疼痛的实际经验之间的差异。我们认为，骨性关节炎的痛感可以独立于进行性软骨退变而发展，关节疼痛的严重程度是由于支配背根神经节感觉神经元的细胞和分子可塑性以及滑膜的病理变化(如滑膜炎、血管生成)所致。我们将确定促进骨性关节炎前伤害性感觉的基本因素，而不依赖于软骨退变的程度。我们的研究也将为开发治疗骨性关节炎症状的临床策略提供重要的实证支持。我们的结果将为主要疾病改变的慢性疼痛机制提供一个新的视角，这些机制伴随着膝骨关节炎的膝关节退变。在更广泛的层面上，这项提议的结果将通过澄清肌肉骨骼组织退化和衰弱的骨性关节炎症状之间的关系，影响我们的概念观点和未来的研究翻译。

DESCRIPTION (provided by applicant): ABSTRACT: Osteoarthritic symptom is the key reason to seek medical assistance, yet there is no effective way to relieve osteoarthritis (OA)-induced pain. Our long term goal is to understand the discrepancy between the degree of cartilage degeneration and the actual experience of joint pain by investigating the neuroanatomical approaches in an experimental OA model followed by validation in human joint tissues. We propose that OA pain sensation can develop independently of progressive cartilage degeneration, and that severity of joint pain is due to cellular and molecular plasticity in the sensory neurons of the innervating dorsal root ganglion and pathological changes in synovium (e.g., synovitis, angiogenesis). We will identify the fundamental factors that facilitate pro- nociception in OA independently of the degree of cartilage degeneration. Our studies will also provide important empirical support for the development of clinical strategies to treat OA symptoms. Our results will provide a novel view of major disease-modified chronic pain mechanisms that accompany degeneration of knee joints in OA. At a broader level, results from this proposal will impact our conceptual perspectives and future research translation by clarifying relationships between musculoskeletal tissue degeneration and debilitating OA symptoms.