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Characterisation of peripheral and central components of the rat monoiodoacetate model of Osteoarthritis

Lockwood, SM; Lopes, DM; McMahon, SB; Dickenson, AH; (2019) Characterisation of peripheral and central components of the rat monoiodoacetate model of Osteoarthritis. Osteoarthritis Cartilage 10.1016/j.joca.2018.12.017. (In press). Green open access

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Abstract

OBJECTIVE: Pain is the main reason patients report Osteoarthritis (OA), yet current analgesics remain relatively ineffective. This study investigated both peripheral and central mechanisms that lead to the development of OA associated chronic pain. DESIGN: The monoiodoacetate (MIA) model of OA was investigated at early (2-6 days post injection) and late (>14 days post injection) time points. Pain-like behaviour and knee histology were assessed to understand the extent of pain due to cartilage degradation. Electrophysiological single-unit recordings were taken from spinal wide dynamic range (WDR) neurons to investigate Diffuse Noxious Inhibitory Controls (DNIC) as a marker of potential changes in descending controls. Immunohistochemistry was performed on dorsal root ganglion (DRG) neurons to assess any MIA induced neuronal damage. Furthermore, qPCR was used to measure levels of glia cells and cytokines in the dorsal horn. RESULTS: Both MIA groups develop pain-like behaviour but only late phase animals display extensive cartilage degradation. Early phase animals have a normally functioning DNIC system but there is a loss of DNIC in late phase animals. We found no evidence for neuronal damage caused by MIA in either group, yet an increase in IL-1β mRNA in the dorsal horn of late phase animals. CONCLUSION: The loss of DNIC in late phase MIA animals suggests an imbalance in inhibitory and facilitatory descending controls, and a rise in the mRNA expression of IL-1β mRNA suggest the development of central sensitisation. Therefore, the pain associated with OA in late phase animals may not be attributed to purely peripheral mechanisms.

Type: Article
Title: Characterisation of peripheral and central components of the rat monoiodoacetate model of Osteoarthritis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.joca.2018.12.017
Publisher version: https://doi.org/10.1016/j.joca.2018.12.017
Language: English
Additional information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Diffuse Noxious Inhibitory Controls, MIA Model, descending controls
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging
URI: https://discovery.ucl.ac.uk/id/eprint/10065880
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