Editorial: Synovitis and Pain Sensitization

Abstract

Arthritis pain is a complex group of symptoms mediated by diverse mechanisms. Osteoarthritis (OA) is commonly considered a mechanical problem, and OA pain results from nociceptive input when a damaged joint is subjected to mechanical stress during weight bearing or movement. However, the experience of pain often bears little relationship to the extent of joint damage as determined by traditional radiography. Factors such as synovitis, osteochondral pathology, and sensitization of both peripheral and central pain pathways each contribute to the quality and severity of OA pain (1,2). Understanding which key aspects of joint pathology lead to arthritis pain is important if we are to develop treatments that will not only maintain joint structure, but also improve symptoms. Neogi et al provide evidence from the large Multicenter Osteoarthritis Study (MOST) prospective cohort that synovitis in knee OA might lead to widespread neuronal sensitization (3). This raises the possibility that targeting synovitis in OA might not only relieve inflammatory pain and progressive joint damage (4), but also prevent pain from becoming chronic, amplified, and spreading beyond the initially affected joint.The development of central sensitization has often been attributed to ongoing nociceptive input in OA. Indeed, augmented central pain processing is associated with more severe pain, and normalization of central pain processing accompanies pain relief after arthroplasty (5,6). However, in inflammatory arthritis models central sensitization develops alongside synovitis (7), and widespread reduced pressure pain thresholds are associated with inflammatory disease activity in rheumatoid arthritis (RA) (8,9). Central sensitization might therefore be mediated by inflammation, rather than its accompanying pain, and widespread augmentation of central pain processing might be driven by circulating factors such as cytokines (10) rather than directly by nociceptive drive. The data presented by Neogi et al support translational relevance to human OA of these findings in RA and in preclinical models. Central sensitization might also be driven by genetic constitution or comorbid fibromyalgia (11) and by concurrent psychological factors such as catastrophizing (12) and distress (13). The prospective study by Neogi and colleagues indicates a likely contribution of synovitis to progressive widespread sensitization, determined by quantitative sensory testing, that is largely independent of these other factors. Further research would be required to determine whether synovitis directly alters central pain processing or is a marker for a subpopulation of patients with OA who have a predisposition to sensitization.Neogi et al suggest that once developed, neuronal sensitization might be unresponsive to reductions in synovitis, emphasizing the potential value of preventative strategies. Reversal of augmented central pain processing following arthroplasty might justify greater optimism for treating those who already have arthritis pain. Lack of associated imp...

CCL2 and CCR2 regulate pain-related behaviour and early gene expression in post-traumatic murine osteoarthritis but contribute little to chondropathy

“…It is nonetheless the case that most patients with severe radiographic changes also show evidence of synovitis by magnetic resonance imaging (MRI), and synovitis probably contributes to pain in these individuals28, 29, 30. Our results show that deletion of CCL2 and to some extent CCR2, affects some of the inflammatory response to joint destabilisation.…”