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

Lookup NU author(s): Dr Lilian NwosuORCiD


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© 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.

Publication metadata

Author(s): Aso K, Shahtaheri SM, Hill R, Wilson D, McWilliams DF, Nwosu LN, Chapman V, Walsh DA

Publication type: Article

Publication status: Published

Journal: Osteoarthritis and Cartilage

Year: 2020

Volume: 28

Issue: 9

Pages: 1245-1254

Print publication date: 01/09/2020

Online publication date: 25/05/2020

Acceptance date: 13/05/2020

ISSN (print): 1063-4584

ISSN (electronic): 1522-9653

Publisher: W.B. Saunders Ltd


DOI: 10.1016/j.joca.2020.05.010

PubMed id: 32470596


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