Contribution of nerves within osteochondral channels to osteoarthritis knee pain in humans and rats.
Aged
Aged, 80 and over
Animals
Arthralgia
/ physiopathology
Asymptomatic Diseases
Calcitonin Gene-Related Peptide
/ metabolism
Cartilage, Articular
/ pathology
Case-Control Studies
Female
Humans
Knee Joint
/ drug effects
Male
Menisci, Tibial
/ surgery
Middle Aged
Nerve Growth Factor
/ metabolism
Osteoarthritis, Knee
/ physiopathology
Peripheral Nerves
/ metabolism
Protein Kinase Inhibitors
/ pharmacology
Rats
Receptor, trkA
/ antagonists & inhibitors
Tibia
/ pathology
Knee osteoarthritis
Nerve
Nerve growth factor
Pain
Subchondral bone
Journal
Osteoarthritis and cartilage
ISSN: 1522-9653
Titre abrégé: Osteoarthritis Cartilage
Pays: England
ID NLM: 9305697
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
04
10
2019
revised:
12
05
2020
accepted:
13
05
2020
pubmed:
30
5
2020
medline:
3
8
2021
entrez:
30
5
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 32470596
pii: S1063-4584(20)31026-8
doi: 10.1016/j.joca.2020.05.010
pii:
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Nerve Growth Factor
9061-61-4
Receptor, trkA
EC 2.7.10.1
Calcitonin Gene-Related Peptide
JHB2QIZ69Z
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1245-1254Informations de copyright
Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest D.A. Walsh: Grants from Arthritis Research UK, while the study was being conducted; grants from Pfizer Ltd, other from Pfizer Ltd, personal fees from GlaxoSmithKline, outside the submitted work. D. F. McWilliams: grants from Pfizer Ltd. The remaining authors have no conflicts of interest to declare.