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Collagen-induced arthritis as a model of hyperalgesia

Inglis, JJ; Notley, CA; Essex, D; Wilson, AW; Feldmann, M; Anand, P; Williams, R; (2007) Collagen-induced arthritis as a model of hyperalgesia. ARTHRITIS RHEUM , 56 (12) 4015 - 4023. 10.1002/art.23063.

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Abstract

Objective. There is a disparity in the animal models used to study pain in rheumatoid arthritis (RA), which tends to be acute in nature, and models used to assess the pathogenesis of RA. The latter models, like human RA, are lymphocyte-driven and polyarthritic. We assessed pain behavior and mechanisms in collagen-induced arthritis (CIA), the model of preclinical arthritis used most commonly in the field of immunology. We then validated the model using anti-tumor necrosis factor (anti-TNF) therapy, which has analgesic effects in models of inflammation as well as in human RA.Methods. CIA was induced in DBA/1 mice by immunization with type 11 collagen at the base of the tail. Swelling and mechanical and thermal hyperalgesia were assessed before and for 28 days after the onset of arthritis. Spontaneous behavior was assessed using an automated activity monitor. Glial activity was assessed by glial fibrillary acidic protein expression, and nerve damage was evaluated by activating transcription factor 3 expression. The actions of anti-TNF therapy on nociception were then evaluated.Results. Arthritis resulted in a decrease in the threshold for thermal and mechanical stimuli, beginning on the day of onset. Decreased spontaneous activity was also observed. A significant increase in the number of hyperplasic spinal cord astrocytes was observed beginning 10 days after the onset of arthritis. Anti-TNF therapy was profoundly analgesic, with an efficacy similar to that of cyclooxygenase 2 inhibition, and reduced astrocyte activity in CIA.Conclusion. This study shows that the CIA model is suitable for testing not only antiinflammatory but also analgesic drugs for potential use in RA, and highlights the importance of using appropriate disease models to assess relevant pain pathways.

Type: Article
Title: Collagen-induced arthritis as a model of hyperalgesia
DOI: 10.1002/art.23063
Keywords: TUMOR-NECROSIS-FACTOR, CHRONIC INFLAMMATORY PAIN, NERVE GROWTH-FACTOR, RHEUMATOID-ARTHRITIS, GENE-EXPRESSION, FACTOR-ALPHA, SPINAL-CORD, TNF-ALPHA, CYTOKINES, MICE
UCL classification: UCL > Provost and Vice Provost Offices
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 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 > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/170887
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