Osteoarthritis (OA) is the most common arthritic disease in the world, leading to debilitating pain and destruction of joint tissues. While pain is the hallmark symptom of osteoarthritis, clear associations between pain and disease processes involved in joint deterioration are lacking. OA pain is multifactorial and may arise from multiple distinct or concurrent mechanisms, and may thus present as different pain sub-types. Several biomarkers developed to reflect important pathological processes are available, and associations between such biomarkers and OA pain may give hints to important pathological features, which have not been possible to assess using clinical, radiographic or magnetic resonance imaging techniques. This review highlights a selection of important, protein-derived biomarkers measured in body fluids from OA patients, which have been associated with different types and aspects of OA pain, and discusses the potential mechanisms behind the associations.

SIGNIFICANCE:
Osteoarthritis (OA) is a heterogenous disease affecting the entire joint, including cartilage, bone and synovium. While pain is the hallmark symptom of osteoarthritis, clear associations between pain and disease processes involved in joint deterioration are lacking. Thus, there is clear need for biomarkers that can accurately describe the underlying processes and distinguish between different disease and pain pathologies. In this review we discuss a selected number of biomarkers which have been directly or indirectly associated with pain mechanisms and development of pain in OA either via structural correlates or as molecular sensitizing agents. We further evaluate the challenges that the OA field faces in the development and application of biomarkers for OA pain.