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Peripheral brain-derived neurotrophic factor contributes to chronic osteoarthritis joint pain

Gowler, Peter R.W.; Li, Li; Woodhams, Stephen G.; Bennett, Andrew J.; Suzuki, Rie; Walsh, David A.; Chapman, Victoria

Authors

LI LI li.li@nottingham.ac.uk
Senior Research Fellow

Rie Suzuki

DAVID WALSH david.walsh@nottingham.ac.uk
Professor of Rheumatology



Abstract

Brain-derived neurotrophic factor (BDNF) and the high-affinity receptor tropomyosin receptor kinase B (TrkB) have important roles in neuronal survival and in spinal sensitization mechanisms associated with chronic pain. Recent clinical evidence also supports a peripheral role of BDNF in osteoarthritis (OA), with synovial expression of TrkB associated with higher OA pain. The aim of this study was to use clinical samples and animal models to explore the potential contribution of knee joint BDNF/TrkB signalling to chronic OA pain. Brain-derived neurotrophic factor and TrkB mRNA and protein were present in knee synovia from OA patients (16 women, 14 men, median age 67 years [interquartile range: 61-73]). There was a significant positive correlation between mRNA expression of NTRK2 (TrkB) and the proinflammatory chemokine fractalkine in the OA synovia. Using the surgical medial meniscal transection (MNX) model and the chemical monosodium iodoacetate (MIA) model of OA pain in male rats, the effects of peripheral BDNF injection, vs sequestering endogenous BDNF with TrkB-Fc chimera, on established pain behaviour were determined. Intra-articular injection of BDNF augmented established OA pain behaviour in MIA rats, but had no effect in controls. Intra-articular injection of the TrkB-Fc chimera acutely reversed pain behaviour to a similar extent in both models of OA pain (weight-bearing asymmetry MIA: -11 ± 4%, MNX: -12 ± 4%), compared to vehicle treatment. Our data suggesting a contribution of peripheral knee joint BDNF/TrkB signalling in the maintenance of chronic OA joint pain support further investigation of the therapeutic potential of this target.

Citation

Gowler, P. R., Li, L., Woodhams, S. G., Bennett, A. J., Suzuki, R., Walsh, D. A., & Chapman, V. (2020). Peripheral brain-derived neurotrophic factor contributes to chronic osteoarthritis joint pain. PAIN, 161(1), 61-73. https://doi.org/10.1097/j.pain.0000000000001694

Journal Article Type Article
Acceptance Date Oct 2, 2019
Online Publication Date Jan 1, 2020
Publication Date 2020-01
Deposit Date Jan 14, 2020
Journal Pain
Print ISSN 0304-3959
Electronic ISSN 1872-6623
Publisher Lippincott, Williams & Wilkins
Peer Reviewed Peer Reviewed
Volume 161
Issue 1
Pages 61-73
DOI https://doi.org/10.1097/j.pain.0000000000001694
Keywords Anesthesiology and Pain Medicine; Neurology; Clinical Neurology
Public URL https://nottingham-repository.worktribe.com/output/3702842
Publisher URL https://journals.lww.com/pain/FullText/2020/01000/Peripheral_brain_derived_neurotrophic_factor.8.aspx

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