TY  - JOUR
N1  - © 2012 Thakur et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3312347

This work was funded by the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
SN  - 1932-6203
ID  - discovery1354302
AV  - public
JF  - PLoS One
N2  - 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.
IS  - 3
A1  - Thakur, M
A1  - Rahman, W
A1  - Hobbs, C
A1  - Dickenson, AH
A1  - Bennett, DL
VL  - 7
Y1  - 2012/03/21/
UR  - http://dx.doi.org/10.1371/journal.pone.0033730
KW  - Activating Transcription Factor 3
KW  -  Animals
KW  -  Anterior Horn Cells
KW  -  Behavior
KW  -  Animal
KW  -  Disease Models
KW  -  Animal
KW  -  Ganglia
KW  -  Spinal
KW  -  Immunohistochemistry
KW  -  Iodoacetates
KW  -  Male
KW  -  Neurons
KW  -  Osteoarthritis
KW  -  Knee
KW  -  Pain
KW  -  Rats
KW  -  Rats
KW  -  Sprague-Dawley
KW  -  Time Factors
TI  - Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis.
ER  -