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Soluble low affinity nerve growth factor receptor (sLNGFR) may regulate pain in knee osteoarthritis


1, 2, 3, 4, 5, 6, 7, 8, 9

 

  1. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and National Institute for Health and Care Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.
  2. Department of Physical Medicine and Rehabilitation, Elisabeth Bruyère Hospital, Ottawa; Bone and Joint Lab, Ottawa Hospital Research Institute, Ottawa, and Ottawa Hospital Research Institute, Ottawa, Canada.
  3. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
  4. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
  5. Tetrad Discovery Ltd., Discovery Park, Sandwich, UK.
  6. The Ottawa Hospital, Critical Care Wing, Ottawa, Canada.
  7. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
  8. Levicept Ltd., Discovery Park, Sandwich, UK.
  9. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and National Institute for Health and Care Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK. d.g.mcgonagle@leeds.ac.uk

CER16929
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PMID: 37976118 [PubMed]

Received: 19/06/2023
Accepted : 25/09/2023
In Press: 08/11/2023

Abstract

OBJECTIVES:
Nerve growth factor β (β-NGF) is a protein which is important to the development of neurons particularly those involved in the transmission of pain and is central to the experience of pain in osteoarthritis (OA). Direct NGF antagonism has been shown to reduce OA pain but is associated with rapidly progressive OA. The aim of the study is to investigate the ability of soluble neurotrophin receptors in the NGF pathway to modulate pain in OA.
METHODS:
Synovial fluid (SF) was obtained from the knee joints of 43 subjects who underwent total knee arthroplasty. Visual analogue scale (VAS) pain scores were obtained prior to surgery. Customised-automated-ELISAs and commercial-ELISAs and LEGENDplex™ were used to measure soluble low-affinity nerve growth factor (LNGFR), soluble tropomyosin receptor kinase (TrkA), proNGF, β-NGF, other neurotrophins (NT) and cytokines including inflammatory marker TNF-α.
RESULTS:
The VAS score positively correlated with β-NGF (r=0.34) and there was positive association trend with neurotrophin-3 (NT-3), BDNF and negative association trend with ProNGF. sLNGFR positively correlated with VAS (r=0.33). The β-NGF/soluble TrkA ratio showed a strong positive correlation with VAS (r=0.80). In contrast, there was no correlation between pain and the β-NGF/sLNGFR ratio (r=-0.08). TNF-α positively correlated with β-NGF (r=0.83), NT-3 (r=0.66), and brain-derived neurotrophic factor (BDNF) (r=0.50) and negatively with ProNGF (r= -0.74) and positively correlated with both soluble TrkA (r=0.62), sLNGFR (r=0.26).
CONCLUSIONS:
This study suggests that endogenous or cleaved sLNGFR, but not soluble TrkA may participate in OA pain modulation thus supporting further research into soluble LNGFR as a therapeutic target in OA.

DOI: https://doi.org/10.55563/clinexprheumatol/163r6k

Rheumatology Article