Osteoarthritis pain mechanisms: basic studies in animal models

Abstract

Osteoarthritis (OA) is a complex and painful disease of the whole joint. At present there are no satisfying agents for treating OA. The current standard of care mainly involves managing and alleviating its symptoms. Mechanisms of OA pain have been studied in rodent knee OA models produced by intra-knee injection of the chondrocyte glycolytic inhibitor mono-iodoacetate, surgery, or spontaneous development in some species. These models are clinically relevant in terms of histological damage and functional changes, and are used to study mechanisms underlying mechanical, thermal, ambulatory, body weight supporting-evoked, and ongoing OA pain. Recent peripheral, spinal, and supraspinal biochemical and electrophysiological studies in these models suggest that peripheral pro-inflammatory mediators and neuropeptides sensitize knee nociceptors. Spinal cytokines and neuropeptides promote OA-associated pain, and peripheral and spinal cannabinoids inhibit OA pain respectively through cannabinoid-1 (CB1) and CB1/CB2 receptors. TRPV1 and metalloproteinases contribute and supraspinal descending facilitation of 5-HT/5-HT 3 receptors may also contribute to OA pain. Conditioned place preference tests demonstrate that OA pain induces aversive behaviors suggesting brain involvement in OA pain. During OA, brain functional connectivity is enhanced, but at present it is unclear how this change is related to OA pain.

A Novel Rat Model of Ankle Osteoarthritis Induced by the Application of Monoiodoacetate

“…Matthew et al [10] further demonstrated the coexistence of increased central sensitization and referred pain, and suggested the existence of a central change in OA similar to that observed with neuropathic pain. Zhang et al [17] reported that OA pain correlated with peripheral and central sensitization, involvement of inflammatory cytokines, neuropeptides, and variety of chemical mediators. Hypersensitivity in OA has therefore been attributed to inflammation and degenerative changes within the ankle joint, as well as the excitability of intra-articular pain related receptors involving joint afferents.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…This is consistent with the observations that capsaicin reduces hyperalgesia and bone damage when given prophylactically (i.e., before MIA injection) in the rat (Kalff et al, 2010); however, in multiple clinical trials it showed no proven clinical benefit in patients with OA (reviewed in Remadevi and Szallasi, 2008). Clearly, OA is a complex disease with redundancy in pain pathways, and TRPV1 is only one of many pain targets in patients with OA (Killock, 2013;Zhang et al, 2013c).…”

The role of transient receptor potential channels in joint diseases

“…This is explained by the fact that pain perception comprises a complex series of neurophysiologic events involving stimulation, tissue response, transmission of pain signal and subsequent modulation of these at both peripheral and central levels (Ito and Creemers, 2013;Schaible, 2012). Inflammatory cytokines are important regulators of these pain mechanisms and their presence is associated with inflammatory pain arising from articular joints and IVDs (Ito and Creemers, 2013;Wuertz et al, 2012;Zhang et al, 2013). Interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α) contribute to disease progression and pain, by acting directly not only as nociceptive triggers, but also by inducing generation of other potentially nociceptive molecules, including nitric oxide and prostaglandin E (Liu et al, 2016;.…”