Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.

Joint degeneration observed in the rat monoiodoacetate (MIA) model of osteoarthritis shares many histological features with the clinical condition. The accompanying pain phenotype has seen the model widely used to investigate the pathophysiology of osteoarthritis pain, and for preclinical screening...

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Main Authors: Matthew Thakur, Wahida Rahman, Carl Hobbs, Anthony H Dickenson, David L H Bennett
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3312347?pdf=render
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spelling doaj-6d9178157d2a4d33bb72a430673b497f2020-11-25T01:56:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0173e3373010.1371/journal.pone.0033730Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.Matthew ThakurWahida RahmanCarl HobbsAnthony H DickensonDavid L H BennettJoint degeneration observed in the rat monoiodoacetate (MIA) model of osteoarthritis shares many histological features with the clinical condition. The accompanying pain phenotype has seen the model widely used to investigate the pathophysiology of osteoarthritis pain, and for preclinical screening of analgesic compounds. We have investigated the pathophysiological sequellae of MIA used at low (1 mg) or high (2 mg) dose. Intra-articular 2 mg MIA induced expression of ATF-3, a sensitive marker for peripheral neuron stress/injury, in small and large diameter DRG cell profiles principally at levels L4 and 5 (levels predominated by neurones innervating the hindpaw) rather than L3. At the 7 day timepoint, ATF-3 signal was significantly smaller in 1 mg MIA treated animals than in the 2 mg treated group. 2 mg, but not 1 mg, intra-articular MIA was also associated with a significant reduction in intra-epidermal nerve fibre density in plantar hindpaw skin, and produced spinal cord dorsal and ventral horn microgliosis. The 2 mg treatment evoked mechanical pain-related hypersensitivity of the hindpaw that was significantly greater than the 1 mg treatment. MIA treatment produced weight bearing asymmetry and cold hypersensitivity which was similar at both doses. Additionally, while pregabalin significantly reduced deep dorsal horn evoked neuronal responses in animals treated with 2 mg MIA, this effect was much reduced or absent in the 1 mg or sham treated groups. These data demonstrate that intra-articular 2 mg MIA not only produces joint degeneration, but also evokes significant axonal injury to DRG cells including those innervating targets outside of the knee joint such as hindpaw skin. This significant neuropathic component needs to be taken into account when interpreting studies using this model, particularly at doses greater than 1 mg MIA.http://europepmc.org/articles/PMC3312347?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Matthew Thakur
Wahida Rahman
Carl Hobbs
Anthony H Dickenson
David L H Bennett
spellingShingle Matthew Thakur
Wahida Rahman
Carl Hobbs
Anthony H Dickenson
David L H Bennett
Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.
PLoS ONE
author_facet Matthew Thakur
Wahida Rahman
Carl Hobbs
Anthony H Dickenson
David L H Bennett
author_sort Matthew Thakur
title Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.
title_short Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.
title_full Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.
title_fullStr Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.
title_full_unstemmed Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.
title_sort characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description Joint degeneration observed in the rat monoiodoacetate (MIA) model of osteoarthritis shares many histological features with the clinical condition. The accompanying pain phenotype has seen the model widely used to investigate the pathophysiology of osteoarthritis pain, and for preclinical screening of analgesic compounds. We have investigated the pathophysiological sequellae of MIA used at low (1 mg) or high (2 mg) dose. Intra-articular 2 mg MIA induced expression of ATF-3, a sensitive marker for peripheral neuron stress/injury, in small and large diameter DRG cell profiles principally at levels L4 and 5 (levels predominated by neurones innervating the hindpaw) rather than L3. At the 7 day timepoint, ATF-3 signal was significantly smaller in 1 mg MIA treated animals than in the 2 mg treated group. 2 mg, but not 1 mg, intra-articular MIA was also associated with a significant reduction in intra-epidermal nerve fibre density in plantar hindpaw skin, and produced spinal cord dorsal and ventral horn microgliosis. The 2 mg treatment evoked mechanical pain-related hypersensitivity of the hindpaw that was significantly greater than the 1 mg treatment. MIA treatment produced weight bearing asymmetry and cold hypersensitivity which was similar at both doses. Additionally, while pregabalin significantly reduced deep dorsal horn evoked neuronal responses in animals treated with 2 mg MIA, this effect was much reduced or absent in the 1 mg or sham treated groups. These data demonstrate that intra-articular 2 mg MIA not only produces joint degeneration, but also evokes significant axonal injury to DRG cells including those innervating targets outside of the knee joint such as hindpaw skin. This significant neuropathic component needs to be taken into account when interpreting studies using this model, particularly at doses greater than 1 mg MIA.
url http://europepmc.org/articles/PMC3312347?pdf=render
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