eprintid: 1354302 rev_number: 40 eprint_status: archive userid: 608 dir: disk0/01/35/43/02 datestamp: 2012-07-31 19:11:14 lastmod: 2021-09-19 23:45:32 status_changed: 2012-07-31 19:11:14 type: article metadata_visibility: show item_issues_count: 0 creators_name: Thakur, M creators_name: Rahman, W creators_name: Hobbs, C creators_name: Dickenson, AH creators_name: Bennett, DL title: Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis. ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G02 keywords: Activating Transcription Factor 3, Animals, Anterior Horn Cells, Behavior, Animal, Disease Models, Animal, Ganglia, Spinal, Immunohistochemistry, Iodoacetates, Male, Neurons, Osteoarthritis, Knee, Pain, Rats, Rats, Sprague-Dawley, Time Factors note: © 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 abstract: 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. date: 2012-03-21 official_url: http://dx.doi.org/10.1371/journal.pone.0033730 vfaculties: VFLS oa_status: green pmcid: PMC3312347 language: eng primo: open primo_central: open_green article_type_text: Journal Article, Research Support, Non-U.S. Gov't verified: verified_manual elements_source: PubMed elements_id: 404203 doi: 10.1371/journal.pone.0033730 pii: PONE-D-11-23096 lyricists_name: Dickenson, Anthony lyricists_name: Rahman, Wahida lyricists_id: AHDIC08 lyricists_id: WRAHM76 full_text_status: public publication: PLoS One volume: 7 number: 3 article_number: e33730 pagerange: - event_location: United States issn: 1932-6203 citation: Thakur, M; Rahman, W; Hobbs, C; Dickenson, AH; Bennett, DL; (2012) Characterisation of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis. PLoS One , 7 (3) , Article e33730. 10.1371/journal.pone.0033730 <https://doi.org/10.1371/journal.pone.0033730>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1354302/1/1354302.pdf