Innervation of the knee and TMJ

膝关节和颞下颌关节的神经支配

• 批准号: 10608403
• 负责人: Kyle D Allen
• 金额: $ 587.9万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-23 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608403
• 关键词: 3-Dimensional; Ablation; Age; Anatomy; Arthralgia; Basic Science; Behavior; Behavioral; Biological Assay; Biological Factors; Bite; Cartilage; Cells; Chronic; Classification; Clinic; Clinical; Clinical Research; Complex; Data; Databases; Degenerative polyarthritis; Dependovirus; Development; Development Plans; Disease; Dyes; Electrophysiology (science); Emerging Technologies; Fascia; Female; Fibrinogen; Gene Expression; Genes; Goals; Human; Image; Image Analysis; Joint Capsule; Joints; Knee; Knee Osteoarthritis; Knee joint; Label; Ligaments; Maps; Measures; Mediating; Modeling; Muscle; Nature; Nerve; Nervous system structure; Neurons; Neurophysiology - biologic function; Operative Surgical Procedures; Pain; Pain Measurement; Pathology; Patient Recruitments; Patients; Pattern; Phenotype; Positioning Attribute; Pre-Clinical Model; Rattus; Replacement Arthroplasty; Resources; Rodent; Sensory; Series; Severities; Signal Transduction; Spinal Ganglia; Stains; Structure of trigeminal ganglion; Symptoms; Synovial Membrane; System; Techniques; Temporomandibular Joint; Temporomandibular Joint Disorders; Temporomandibular joint osteoarthritis; Tendon structure; Testing; Tissues; Tracer; Translating; adeno-associated viral vector; age related; arthropathies; base; bone; clinical pain; clinically relevant; clinically significant; design; disability; experience; histological slides; human tissue; improved; joint function; joint injury; male; meniscus injury; nerve supply; novel strategies; novel therapeutics; pain relief; pre-clinical; preclinical study; promoter; relating to nervous system; response; sex; single-cell RNA sequencing; technology development; transcriptome; transcriptome sequencing; transcriptomics

The over-arching goal for the RE-JOIN Consortium is to define how the neurons that mediate chronic joint pain innervate different articular and peri-articular tissues, with a focus on the knee and temporomandibular joint (TMJ). With an improved understanding of how different neural subtypes distribute through the joint and how these subtypes change with age and disease, new therapies can be developed to reduce the heavy burden of chronic joint pain. To achieve this goal, our team will focus on advancing our understanding of pathology-pain relationships in the knee and TMJ by combining expertise in neural tracing, 3-dimensional imaging, and evaluations of chronic joint pain and disability. Our proposal brings together a highly collaborative team that spans basic science and clinical research with extensive experience in both the knee and TMJ, allowing us to evaluate shared vs. joint-specific shifts in innervation networks and the development of chronic joint pain. Specifically, our team will first use neural tracing dyes to identify the cell bodies in the dorsal root ganglia and trigeminal ganglia that project to the muscle, bone, or intra-articular joint tissues. These neurons will then be evaluated for their function using electrophysiologic tests and their transcriptome using single cell RNA-Seq. By overlapping neural function with gene expression, we will identify promoter targets and design adeno-associated virus (AAV) vectors to produce fluorescent labels alongside the expression of these targets. Importantly, this approach will allow us to develop AAV-based tracers for specific functional neural subtypes, as well as combine traditional markers of functional subtypes with any newly identified markers that describe how the neuron changes with age, sex, and osteoarthritis (OA) severity. Using these tracers, we will then evaluate the distribution of functional neural subtypes throughout the joint (including bone, cartilage, synovium, joint capsule, ligament, tendon, fascia, and muscle) and how these innervation networks change with age, sex, and OA severity. Moreover, these tracers will be used to evaluate how joint innervation adapts following the application of two neural ablation techniques for pain relief in the knee and TMJ. To evaluate the clinical significance of our preclinical studies, innervation changes will be assessed in tissues collected from patients undergoing total joint replacement of the knee or TMJ. In all of our studies, joint innervation will be paired with detailed analyses of joint pain and disability. In rodents, these analyses will include detailed behavioral characterizations; in patients, these analyses will include quantitative sensory tests and other assessments of joint function. Combined, this approach will allow us to evaluate pathology-pain relationships related to joint innervation from the preclinical model to the clinic.

RE-JOIN联盟的首要目标是定义神经元如何进行调解