BDNF sensitizes bone and joint afferent neurons at different stages of MIA-induced osteoarthritis.

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  • Additional Information
    • Source:
      Publisher: Elsevier Science Country of Publication: United States NLM ID: 8504048 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2763 (Electronic) Linking ISSN: 18732763 NLM ISO Abbreviation: Bone Subsets: MEDLINE
    • Publication Information:
      Publication: New York : Elsevier Science
      Original Publication: Elmsford, NY : Pergamon Press, c1985-
    • Subject Terms:
      Brain-Derived Neurotrophic Factor*/metabolism ; Receptor, trkB*/metabolism ; Osteoarthritis*/pathology ; Osteoarthritis*/metabolism ; Bone and Bones*/pathology ; Bone and Bones*/metabolism ; Neurons, Afferent*/metabolism ; Neurons, Afferent*/pathology ; Neurons, Afferent*/drug effects; Animals ; Male ; Iodoacetic Acid ; Rats, Sprague-Dawley ; Rats ; Joints/pathology ; Joints/innervation ; Joints/metabolism ; Signal Transduction/drug effects ; Knee Joint/pathology ; Knee Joint/innervation ; Knee Joint/metabolism
    • Abstract:
      There is emerging evidence that Brain Derived Neurotrophic Factor (BDNF), and one of its receptors TrkB, play important roles in the pathogenesis of osteoarthritis (OA) pain. Whilst these studies clearly highlight the potential for targeting BDNF/TrkB signaling to treat OA pain, the mechanism for how BDNF/TrkB signaling contributes to OA pain remains unclear. In this study, we used an animal model of mono-iodoacetate (MIA)-induced OA, in combination with electrophysiology, behavioral testing, Western blot analysis, and retrograde tracing and immunohistochemistry, to identify roles for BDNF/TrkB signaling in the pathogenesis of OA pain. We found that: 1) TrkB is expressed in myelinated medium diameter neurons that innervate the knee joint and bone in naïve animals; 2) peripheral application of BDNF increases the sensitivity of Aδ, but not C knee joint and bone afferent neurons, in response to mechanical stimulation, in naïve animals; 3) BDNF expression increases in synovial tissue in early MIA-induced OA, when pathology is confined to the joint, and in the subchondral bone in late MIA-induced OA, when there is additional damage to the surrounding bone; and 4) TrkB inhibition reverses MIA-induced changes in the sensitivity of Aδ but not C knee joint afferent neurons early in MIA-induced OA, and Aδ but not C bone afferent neurons late in MIA-induced OA. Our findings suggest that BDNF/TrkB signaling may have a role to play in the pathogenesis of OA pain, through effects on knee joint afferent neurons early in disease when there is inflammation confined to the joint, and bone afferent neurons late in disease when there is involvement of damage to subchondral bone. Targeted manipulation of BDNF/TrkB signaling may provide therapeutic benefit for the management of OA pain.
      Competing Interests: Declaration of competing interest None.
      (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: BDNF; Nociceptors; Osteoarthritis; Pain; Sensory neurons; TrkB
    • Accession Number:
      0 (Brain-Derived Neurotrophic Factor)
      EC 2.7.10.1 (Receptor, trkB)
      WF5188V710 (Iodoacetic Acid)
    • Publication Date:
      Date Created: 20240919 Date Completed: 20241018 Latest Revision: 20241029
    • Publication Date:
      20241031
    • Accession Number:
      10.1016/j.bone.2024.117260
    • Accession Number:
      39299629