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Contribution of nerves within osteochondral channels to osteoarthritis knee pain in humans and rats

Aso, K.; Shahtaheri, S. M.; Hill, R.; Wilson, D.; McWilliams, D. F.; Nwosu, L. N.; Chapman, V.; Walsh, D. A.


K. Aso

S. M. Shahtaheri

R. Hill

D. Wilson

L. N. Nwosu

Professor of Rheumatology


© 2020 Osteoarthritis Research Society International Objectives: Subchondral bone may contribute to knee osteoarthritis (OA) pain. Nerve growth factor (NGF) can stimulate nerve growth through TrkA. We aimed to identify how sensory nerve growth at the osteochondral junction in human and rat knees associates with OA pain. Methods: Eleven symptomatic chondropathy cases were selected from people undergoing total knee replacement for OA. Twelve asymptomatic chondropathy cases who had not presented with knee pain were selected post-mortem. OA was induced in rat knees by meniscal transection (MNX) and sham-operated rats were used as controls. Twice-daily oral doses (30 mg/kg) of TrkA inhibitor (AR786) or vehicle were administered from before and up to 28 days after OA induction. Joints were analysed for macroscopic appearances of articular surfaces, OA histopathology and calcitonin gene-related peptide-immunoreactive (CGRP-IR) sensory nerves in medial tibial plateaux, and rats were assessed for pain behaviors. Results: The percentage of osteochondral channels containing CGRP-IR nerves in symptomatic chondropathy was higher than in asymptomatic chondropathy (difference: 2.5% [95% CI: 1.1–3.7]), and in MNX-than in sham-operated rat knees (difference: 7.8% [95%CI: 1.7–15.0]). Osteochondral CGRP-IR innervation was significantly associated with pain behavior in rats. Treatment with AR786 prevented the increase in CGRP-IR nerves in osteochondral channels and reduced pain behavior in MNX-operated rats. Structural OA was not significantly affected by AR786 treatment. Conclusions: CGRP-IR sensory nerves within osteochondral channels are associated with pain in human and rat knee OA. Reduced pathological innervation of the osteochondral junction might contribute to analgesic effects of reduced NGF activity achieved by blocking TrkA.


Aso, K., Shahtaheri, S. M., Hill, R., Wilson, D., McWilliams, D. F., Nwosu, L. N., …Walsh, D. A. (2020). Contribution of nerves within osteochondral channels to osteoarthritis knee pain in humans and rats. Osteoarthritis and Cartilage,

Journal Article Type Article
Acceptance Date May 14, 2020
Online Publication Date May 26, 2020
Publication Date May 26, 2020
Deposit Date Jun 8, 2020
Publicly Available Date May 27, 2021
Journal Osteoarthritis and Cartilage
Print ISSN 1063-4584
Electronic ISSN 1522-9653
Publisher Elsevier
Peer Reviewed Peer Reviewed
Keywords Rheumatology; Orthopedics and Sports Medicine; Biomedical Engineering
Public URL
Publisher URL
Additional Information OAC10246


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