The sources of pain in osteoarthritis: a pathophysiological review

Abstract

summaryThe pain of osteoarthritis (OA) has multifaceted etiologies within and outside the joint. It is believed to be driven by both nociceptive and neuropathic mechanisms, as well as abnormal excitability in the pain pathways of the peripheral and central nervous system. Inflammation in the joint triggers a cascade of events that leads to peripheral sensitization, increased sensitivity of nociceptive primary afferent neurons, and hyperexcitability of the nociceptive neurons in the central nervous system. Pain receptors have been found in the synovium, ligaments, capsule, subchondral bone and surrounding tissues, with the exception of articular cartilage. The bone-related causes of pain in OA include subchondral microfractures, bone stretching with elevation of the periosteum due to osteophyte growth, bone remodeling and repair, bone marrow lesions, and bone angina caused by decreased blood flow and increased intra-osseous pressure. Central factors alter pain processing by setting the gain in such a way that, when a peripheral input is present, it is processed against a background of central factors that can enhance or diminish the experience of pain. As a complex phenomenon with a strong subjective component, pain can also be influenced by the nature of the underlying disease, personal predisposition (biological and psychological), and environmental and psychosocial factors. This review examines the current literature regarding the sources and mechanisms of pain in OA.

Efficacy of CR4056, a first-in-class imidazoline-2 analgesic drug, in comparison with naproxen in two rat models of osteoarthritis

“…Oral CR4056 reduced also hind limb weight-bearing imbalance after repeated daily treatment from day 28 to day 42 after MMT surgery. Consistently with what happens in the human disease,2,34 both an inflammatory component and a neuropathic component of pain appear to be involved in these experimental paradigms,35 where joint damage is induced by transection of the medial collateral ligament and medial meniscus of the femoro-tibial joint and by intra-articular injection of MIA, respectively, with consequent pain behavior.…”

“…OA pain represents the most disabling symptom for patients and it is the most prevalent form of chronic musculoskeletal pain. In particular, OA pain is defined by peripheral and central sensitization and is driven by both nociceptive and neuropathic mechanisms 2. It has long been established that there is poor correlation between the clinical symptoms of OA and joint structure changes, radiologically assessed 3.…”

The therapeutic potential of interleukin-10 in neuroimmune diseases

“…synovial membrane and chondrocytes) and ongoing pain. Although the precise etiology of OA is unknown, it is thought to involve degradation of cartilage that leads to tissue damage, inflammation, and pain with resulting alterations in central nervous system function such as peripheral and central sensitization (for review, see Fernandes et al, 2002; Martel-Pelletier et al, 1999; Salaffi et al, 2014; Taruc-Uy and Lynch, 2013). OA is the leading cause of pain and disability in the world, most commonly affecting the elderly but also occurring in younger populations often following injury or intense physical activity (Sharma et al, 2006).…”

Predictors of Osteoarthritis Pain: the Importance of Resilience

“…Biomechanical changes are a prime characteristic of OA development, including compromised hyaline articular cartilage in the joints, joint-line spacing, sub-chondral bone, development of osteophytes, cyst formation, corresponding damage to ligaments, and diminished joint/muscle strength [11]. Although it is generally conceived that the degree of joint and tissue damage should be proportional to the amount of pain and disability arising from OA, this is not always the case.…”