Osteoarthritis: the genesis of pain

Abstract

OA is a painful joint disease that predominantly affects the elderly. Pain is the primary symptom of OA, and it can present as either intermittent or constant. OA pain mechanisms are complex and have only recently been determined. Both peripheral and central processes are involved in creating the OA pain experience, making targeted therapy problematic. Nociceptive, inflammatory and neuropathic pains are all known to occur in OA, but to varying degrees in a patient- and time-specific manner. A better understanding of these multifactorial components of OA pain will lead to the development of more effective and safer pain treatments.

Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

“…Pain is the most prominent symptom of knee osteoarthritis (KOA) and the major driver of clinical decision-making. Despite great progress in the understanding of the molecular and cellular 3 mechanisms of KOA, the treatment of pain is still a challenge in the clinic (1)(2)(3)(4). Therefore, etiological investigation of pain is not only helpful for understanding KOA but also critical for developing new medications to relieve it.…”

Topical Diclofenac, an Efficacious Treatment for Osteoarthritis: A Narrative Review

“…While bone remodeling, loss of cartilage, and narrowing of the joint space are the characteristic morphological changes observed in OA, pain often is associated with the presence of inflammation (synovitis) [4,6,84]. In such cases, peripheral nerves in the various degenerating joint tissues become exposed to the intraarticular environment rich in cytokines, chemokines, proteases, prostaglandins, and neuropeptides, which serve as ligands for nociceptors [86,[90][91][92]. Ligand binding lowers the threshold of these receptors and sensitizes the peripheral neurons, such that even normal joint movement triggers a pain response [86,87,93].…”

“…In addition to nociceptive pain, neuropathic pain may result from direct damage to the nerves in the injured joint, dorsal root ganglia, and spinal cord [11,96,97]. Neuropathic pain is not responsive to NSAIDs [92].…”

“…Central sensitization can be another major component of OA pain, manifesting as increased sensitivity to noxious stimuli (hyperalgesia) or interpretation of non-noxious stimuli as painful (allodynia) [27,92]. Although there is some evidence that diclofenac crosses the blood-brain barrier [98,99], low concentrations are likely to enter the central nervous system following topical administration given the limited systemic exposure associated with topical use.…”

“…Thus, OA pain may have peripheral elements (e.g., inflammation, sensitization of peripheral neurons, direct damage to nerves) as well as central components (e.g., hyperalgesia and allodynia), and these heterogeneous underlying mechanisms may respond differently to treatment [5,92,100]. Patients with earlier-stage OA pain related to active inflammation, particularly inflammatory mediators downstream of PGE2, would likely have the best response to topical NSAIDs based on their mechanism of action, but this remains to be confirmed.…”