Peripheral Mechanisms Contributing to Osteoarthritis Pain

  • Delfien Syx
  • Phuong B. Tran
  • Rachel E. Miller
  • Anne-Marie MalfaitEmail author
Chronic Pain (R Staud, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Chronic Pain


Purpose of Review

Osteoarthritis (OA) is the most common form of arthritis and a major source of pain and disability worldwide. OA-associated pain is usually refractory to classically used analgesics, and disease-modifying therapies are still lacking. Therefore, a better understanding of mechanisms and mediators contributing to the generation and maintenance of OA pain is critical for the development of efficient and safe pain-relieving therapies.

Recent Findings

Both peripheral and central mechanisms contribute to OA pain. Clinical evidence suggests that a strong peripheral nociceptive drive from the affected joint maintains pain and central sensitization associated with OA. Mediators present in the OA joint, including nerve growth factor, chemokines, cytokines, and inflammatory cells can contribute to sensitization. Furthermore, structural alterations in joint innervation and nerve damage occur in the course of OA.


Several interrelated pathological processes, including joint damage, structural reorganization of joint afferents, low-grade inflammation, neuroplasticity, and nerve damage all contribute to the pain observed in OA. It can be anticipated that elucidating exactly how these mechanisms are operational in the course of progressive OA may lead to the identification of novel targets for intervention.


Osteoarthritis Pain Peripheral Sensitization Inflammation Innervation 


Funding Information

Delfien Syx is a postdoctoral fellow of the Research Foundation—Flanders (FWO). Rachel Miller is supported by the US National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS) (K01AR070328). Anne-Marie Malfait (R01AR064251 and R01AR060364) is supported by NIAMS.

Compliance with Ethical Standards

Conflict of Interest

Dr. Malfait reports personal fees from Regeneron, personal fees from Eli Lilly, personal fees from Pfizer, personal fees from Galapagos, outside the submitted work.

Delfien Syx, Phuong B. Tran and Rachel E. Miller declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Delfien Syx
    • 1
    • 2
  • Phuong B. Tran
    • 2
  • Rachel E. Miller
    • 2
  • Anne-Marie Malfait
    • 2
    Email author
  1. 1.Center for Medical GeneticsGhent UniversityGhentBelgium
  2. 2.Department of Internal Medicine, Division of RheumatologyRush University Medical CenterChicagoUSA

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