The innate immune response as a mediator of osteoarthritis pain

R. J. Miller, A. M. Malfait, R. E. Miller*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

59 Scopus citations


In this narrative review, we discuss the emerging role of innate immunity in osteoarthritis (OA) joint pain. First, we give a brief description of the pain pathway in the context of OA. Then we consider how neuro-immune signaling pathways may promote OA pain. First, activation of neuronal Pattern Recognition Receptors by mediators released in a damaged joint can result in direct excitation of nociceptors, as well as in production of chemokines and cytokines. Secondly, indirect neuro-immune signaling may occur when innate immune cells produce algogenic factors, including chemokines and cytokines, that act on the pain pathway. Neuro-immune crosstalk occurs at different levels of the pathway, starting in the joint but also in the innervating dorsal root ganglia and in the dorsal horn. Synovitis is characterized by recruitment of immune cells, including macrophages, mast cells, and CD4+ lymphocytes, which may contribute to nociceptor sensitization and OA pain through production of algogenic factors that amplify the activation of sensory neurons. We discuss examples where this scenario has been suggested by findings in human OA and in animal models. Overall, increasing evidence suggests that innate immune pathways play an initiating as well as facilitating role in pain, but information on how these pathways operate in OA remains limited. Since these innate pathways are eminently targetable, future studies in this area may provide fruitful leads towards a better management of symptomatic OA.

Original languageEnglish (US)
Pages (from-to)562-571
Number of pages10
JournalOsteoarthritis and Cartilage
Issue number5
StatePublished - May 2020


  • Innate immunity
  • Neuroinflammation
  • Osteoarthritis
  • Pain
  • Sensitization
  • Toll-like receptors

ASJC Scopus subject areas

  • Biomedical Engineering
  • Rheumatology
  • Orthopedics and Sports Medicine


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