Towards a mechanism-based approach to pain management in osteoarthritis

KEY POINTS * Current evidence supports the idea that osteoarthritis (OA) pain is generated and maintained through continuous nociceptive input from the joint * Chronic OA pain is associated

with changes in the central nervous system (CNS); these changes are reversible, reflecting the plasticity of the CNS and the requirement for continuous input from the periphery * Antibodies

to nerve growth factor, which do not cross the blood–brain barrier and therefore act entirely through effects in the periphery, are effective at relieving OA pain * OA pain pathways can also

respond to modulation centrally, as exemplified by data from OA pain trials with duloxetine, thus offering opportunity for the identification of new targets for pain relief * Heterogeneity

in the clinical presentation of OA pain and in the response to analgesic therapies suggests that, in the future, distinct mechanism-based therapeutic approaches could be tailored to specific

subsets of patients ABSTRACT Pain is the defining symptom of osteoarthritis (OA), yet available treatment options, of which NSAIDs are the most common, provide inadequate pain relief and

are associated with serious health risks when used long term. Chronic pain pathways are subject to complex levels of control and modulation, both in the periphery and in the central nervous

system. Ongoing clinical and basic research is uncovering how these pathways operate in OA. Indeed, clinical investigation into the types of pain associated with progressive OA, the presence

of central sensitization, the correlation with structural changes in the joint, and the efficacy of novel analgesics affords new insights into the pathophysiology of OA pain. Moreover,

studies in disease-specific animal models enable the unravelling of the cellular and molecular pathways involved. We expect that increased understanding of the mechanisms by which chronic

OA-associated pain is generated and maintained will offer opportunities for targeting and improving the safety of analgesia. In addition, using clinical and genetic approaches, it might

become possible to identify subsets of patients with pain of different pathophysiology, thus enabling a tailored approach to pain management. Access through your institution Buy or subscribe

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CAUSAL ROLE OF BRAIN CIRCUITS IN OSTEOARTHRITIS PAIN Article 31 March 2025 NOCICEPTIVE MECHANISMS DRIVING PAIN IN A POST-TRAUMATIC OSTEOARTHRITIS MOUSE MODEL Article Open access 17

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A.-M. Malfait acknowledges funding from the US National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR060364 and R01AR064251) and from the

Arthritis Foundation. The funding sources had no role in the preparation of this publication. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medicine, and Department of

Biochemistry, Section of Rheumatology, Rush University Medical Center, 1611 W. Harrison Street, Chicago, 60612, IL, USA Anne-Marie Malfait * Department of Physical Medicine and

Rehabilitation and Department of Internal Medicine, Northwestern University Feinberg School of Medicine, 710 N. Lake Shore Drive, Chicago, 60611, IL, USA Thomas J. Schnitzer Authors *

Anne-Marie Malfait View author publications You can also search for this author inPubMed Google Scholar * Thomas J. Schnitzer View author publications You can also search for this author

inPubMed Google Scholar CONTRIBUTIONS Both authors contributed substantially to all aspects of the preparation of this manuscript. CORRESPONDING AUTHOR Correspondence to Thomas J. Schnitzer.

ETHICS DECLARATIONS COMPETING INTERESTS A. M. Malfait declares that she has acted as a consultant for Allergan. T. J. Schnitzer declares that he has acted as a consultant for Pfizer,

Janssen and Regeneron, and has received research funding from Pfizer and Lilly. POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR TABLE 1 RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Malfait, AM., Schnitzer, T. Towards a mechanism-based approach to pain management in osteoarthritis. _Nat Rev Rheumatol_ 9, 654–664 (2013).

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