Peripheral Mechanisms Contributing to Osteoarthritis Pain

Abstract

Both peripheral and central mechanisms contribute to OA pain. Clinical evidence suggests that a strong peripheral nociceptive drive from the affected joint maintains pain and central sensitization associated with OA. Mediators present in the OA joint, including nerve growth factor, chemokines, cytokines, and inflammatory cells can contribute to sensitization. Furthermore, structural alterations in joint innervation and nerve damage occur in the course of OA. Several interrelated pathological processes, including joint damage, structural reorganization of joint afferents, low-grade inflammation, neuroplasticity, and nerve damage all contribute to the pain observed in OA. It can be anticipated that elucidating exactly how these mechanisms are operational in the course of progressive OA may lead to the identification of novel targets for intervention.

Adipose Tissue is a Critical Regulator of Osteoarthritis

“…Despite exhibiting low-level systemic inflammation (4, 7-9), metabolic disturbance (1, 3), insulin resistance (22), sclerotic bone (11), muscle weakness (3,6), reduced activity (25), synovial inflammation (1, 26), LD mice were protected from cartilage damage. Because increased pain and hyperalgesia are the primary clinical symptoms of OA (27), we also assessed two pain-related outcomes: knee hyperalgesia and tactile allodynia, and observed that consistent with a protection against structural damage, LD mice are also protected from the onset of these pain-related outcomes with DMM. Remarkably, the transplantation of a small amount of adipose tissue mitigated or reversed these contributing factors and restored susceptibility to cartilage damage and knee hyperalgesia in transplanted LD mice.…”

Mechanisms Underlying Bone and Joint Pain

“…fibroblasts, chondrocytes), blood, and local and migrating inflammatory cells [57, 47, 58, 59]. These factors may promote disease progression and pathology in disease states such as arthritis or cancer-induced bone pain.…”

“…Much has been learned about the impact of many of the factors that are released by local tissues, such as ATP, ADP, endothelins, bradykinin, and growth factors [7, 12, 47, 58, 80]. These factors have been shown to act both directly on neurons to activate them and to alter the properties of the neurons.…”

“…These factors have been shown to act both directly on neurons to activate them and to alter the properties of the neurons. These actions including lowering of activation thresholds and increased in responses are key characteristics of peripheral sensitization [7, 12, 58]. Several factors including proinflammatory cytokines (e.g.…”

“…IL-1β, TNFα, IL-6) have been shown to be catabolic and may enhance bone resorption promoting underlying pathology [82]. Mechanisms underlying peripheral sensitization include translation and trafficking of transducer channels as well as phosphorylation of transducer channels such as TRPV1 resulting in altered activation thresholds and increased transfer of cations allowing for enhanced depolarization of the neurons and amplified signaling [12, 7, 58]. Similarly, increased translation and trafficking of sodium channels resulting in amplified action potentials and increased numbers and phosphorylation of calcium channels result in enhanced neurotransmitter release from afferent terminals within the spinal cord [83, 84].…”