The importance of central sensitization for clinical trials of Disease Modifying Osteoarthritis drugs (DMOADs)

Walsh, David A; McWilliams, Daniel F

Abstract

Osteoarthritis (OA) pain is associated with structural changes in the joint, which are usually quantified by imaging techniques. It is anticipated that structural disease modifying OA drugs (DMOADs) would reduce the burden of OA pain. However, nociceptive pain is moderated by the central nervous system. Central sensitization, increased activity in central nervous system neurones in response to a standard nociceptive input, is one reason why disease modification might not effectively relieve OA pain. Central sensitization may result from facilitated central neuronal activity, or inadequate inhibition by endogenous analgesic mechanisms. It changes the experience of pain: its severity, distribution and qualities, and its emotional and cognitive dimensions. Central sensitization can be a barrier to analgesic benefit from treatments directed at joint structure, and central pain processing can obscure analgesic benefit from structural modification in randomised controlled trials. Indices of central pain hypersensitivity might reflect central sensitization in humans. They include self-report questionnaires such as the Central Aspects of Pain (CAP) and short form Central Sensitization Inventory (CSI-9), and quantitative sensory testing (QST) modalities of Pressure Pain detection Thresholds distant to the affected joint, Temporal Summation, and Conditioned Pain Modulation. Understanding, measuring, managing and adjusting for central pain hypersensitivity should increase the power of clinical trials to demonstrate that DMOADs not only improve joint imaging outcomes, but also improve pain, the predominant clinical problem of OA.

Citation

Walsh, D. A., & McWilliams, D. F. (2025). The importance of central sensitization for clinical trials of Disease Modifying Osteoarthritis drugs (DMOADs). Osteoarthritis Imaging, 5(1), Article 100261. https://doi.org/10.1016/j.ostima.2025.100261

• Journal Article Type: Article
• Acceptance Date: Feb 14, 2025
• Online Publication Date: Feb 18, 2025
• Publication Date: 2025-03
• Deposit Date: Feb 23, 2025
• Publicly Available Date: Feb 28, 2025
• Journal: Osteoarthritis Imaging
• Print ISSN: 2772-6541
• Electronic ISSN: 2772-6541
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 1
• Article Number: 100261
• DOI: https://doi.org/10.1016/j.ostima.2025.100261
• Keywords: pain, nociplastic, central sensitization
• Public URL: https://nottingham-repository.worktribe.com/output/45599686
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S2772654125000017?via%3Dihub
• Additional Information: This article is maintained by: Elsevier; Article Title: The importance of central sensitization for clinical trials of Disease Modifying Osteoarthritis drugs (DMOADs); Journal Title: Osteoarthritis Imaging; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.ostima.2025.100261; Content Type: article; Copyright: © 2025 The Authors. Published by Elsevier Ltd on behalf of International Society of Osteoarthritis Imaging.