Therapeutic options for targeting inflammatory osteoarthritis pain


Pain is the major symptom of osteoarthritis (OA) and is an important factor in strategies to manage this disease. However, the current standard of care does not provide satisfactory pain relief for many patients. The pathophysiology of OA is complex, and its presentation as a clinical syndrome is associated with pathologies of multiple joint tissues. Inflammation is associated with both OA pain and disease outcome and is therefore a major treatment target for OA and OA pain. Unlike TNF inhibitors and IL-1 inhibitors, established drugs such as glucocorticoids and methotrexate can reduce OA pain. Although central nociceptive pathways contribute to OA pain, crosstalk between the immune system and nociceptive neurons is central to inflammatory pain; therefore, new therapies might target this crosstalk. Newly identified drug targets, including neurotrophins and the granulocyte–macrophage colony-stimulating factor (GM-CSF)–CC-chemokine ligand 17 (CCL17) chemokine axis, offer the hope of better results but require clinical validation.

Key points

  • Osteoarthritis (OA) pain is a financial, physical and psychological burden globally.

  • Inflammation is often associated with OA pain and the development of OA.

  • Pathological changes in central nociceptive pathways contribute to OA pain.

  • Bidirectional crosstalk between the immune and nervous systems regulates OA pain.

  • New therapeutics that target inflammation and the crosstalk between the immune and nervous systems are being developed to prevent and treat OA pain.

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Fig. 1: The joint–spine–brain connection in OA nociception: anatomy of the basic pain pathway from the periphery to the brain.
Fig. 2: Crosstalk between non-neuronal cells and nociceptive neurons.
Fig. 3: A GM-CSF–CCL17 axis in inflammatory OA pain and disease.


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P.G.C. acknowledges that his research is supported by the UK National Institute of Health Research (NIHR) Leeds Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the UK National Health Service (NHS), the NIHR or the Department of Health.

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Nature Reviews Rheumatology thanks R. Loeser and the other anonymous reviewer(s), for their contribution to the peer review of this work.

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P.G.C. and P.P.T researched data for the article. All authors contributed to discussions of its content and the writing and review or editing of the manuscript before submission.

Correspondence to Paul P. Tak.

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P.G.C. declares that he has participated in speakers bureaus or is on advisory boards for AbbVie, BMS, Flexion Therapeutics, GSK, Merck Serono, Novartis, Pfizer, Roche and Samumed. J.A.H. declares that he has been a consultant for GSK. P.P.T. declares that he was an employee and shareholder of GSK and is presently non-executive director of Levicept. A.D.C. declares no competing interests.

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A family of proteins that regulate the development, maintenance and function of the nervous system.

Action potentials

A rapid rise and subsequent fall in voltage or membrane potential across a cellular membrane that occurs when a neuron sends information down an axon, away from the cell body.

Peak dose

After administration, the highest concentration of the drug reached in the body.


When a patient stops taking medication before beginning a drug treatment trial.

Intention-to-treat analysis

A method for analysing results in prospective randomized studies in which all participants who are randomized are included in the statistical analysis and are analysed according to the group they were originally assigned, regardless of the treatment they received.

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