Molecular Pathways Involved in Knee Pain

Knee osteoarthritis (OA) is the most common form of arthritis and the most common cause of knee pain in the world. The rate of knee arthritis is as high as that of cardiac disease and is the most common problem in individuals over the age of 65. Central Sensitization (CS) is a marker of widespread pain sensitivity that can occur throughout the central nervous system distribution, leading to changes in the spinal cord as well as in the brain. The presence of CS increases the complexity of the clinical picture and can negatively affect treatment outcomes. CS is present in >20% of patients suffering from knee OA indicating that in the majority of individuals suffering with painful knee OA, knee pain should be related to molecular changes in the joint. CS might be also associated with discrete synovial fluid proteomic signatures due to the generation by the joint of chemical mediators (e.g. nerve growth factor) that drive CS, or CS might moderate the relationship between synovial fluid proteomic signatures and symptoms due to alterations in pain processing. The aim of this study is to explore the potential molecular links between pain and structure on knee pain using synovial fluid proteomics. A secondary purpose is to explore the association of knee pain with biomarkers of stress, metabolism and dietary habits. In a single session, ultrasound-guided synovial fluid, blood urine and saliva extraction, clinical assessment, completion of a questionnaire booklet and knee x-rays will be conducted. The clinical assessment will measure three features of central sensitisation (sensitivity to blunt pressure on the most painful knee, changes in pain felt during repeated light pricking of the knee skin, and reduction in pain that accompanies inflation of a blood pressure cuff on the non-dominant arm), features of leg strength (dynamometer, time up-and-go test) and features of balance (sway). Participant involvement at each session is expected to last less than 3 hours. Individuals over 45 having complaints of knee pain for 3-6 months are eligible to participate. The clinical assessments, questionnaire completion and subsequent statistical analysis are expected to be completed within 18 months of study commencement. The findings can provide more insight into the traits of knee pain, allow the examination of possible correlations to each other, and highlight potential detrimental effects of them on knee joint health.