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Dose-dependent expression of neuronal injury markers during experimental osteoarthritis induced by monoiodoacetate in the rat

Joana Ferreira-Gomes*, Sara Adães, Raquel Meireles Sousa, Marcelo Mendonça and José Manuel Castro-Lopes

Author Affiliations

Department of Experimental Biology, Faculty of Medicine of Porto and IBMC - Institute for Molecular and Cell Biology, University of Porto, Alameda Prof. Hernani Monteiro, Porto, 4200-319, Portugal

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Molecular Pain 2012, 8:50  doi:10.1186/1744-8069-8-50

Published: 8 July 2012



It was recently reported that the mono-iodoacetate (MIA) experimental model of osteoarthritis (OA) courses with changes of neurons innervating the affected joints that are commonly interpreted as a neuronal response to axonal injury. To better characterize these changes, we evaluated the expression of two markers of neuronal damage, ATF-3 and NPY, and the growth associated protein GAP-43, in primary afferent neurons of OA animals injected with three different doses of MIA (0.3, 1 or 2 mg). Measurements were performed at days 3, 7, 14, 21 and 31 post-MIA injection.


OA animals showed the characteristic histopathological changes of the joints and the accompanying nociceptive behaviour, evaluated by the Knee-Bed and CatWalk tests. An increase of ATF-3 expression was detected in the DRG of OA animals as early as 3 days after the injection of 1 or 2 mg of MIA and 7 days after the injection of 0.3 mg. NPY expression was increased in animals injected with 1 or 2 mg of MIA, at day 3 or in all time-points, respectively. From day 7 onwards there was a massive increase of GAP-43 expression in ATF-3 cells.


The expression of the neuronal injury markers ATF-3 and NPY as well as an up-regulation of GAP-43 expression, indicative of peripheral fibre regeneration, suggests that axonal injury and a regeneration response may be happening in this model of OA. This opens new perspectives in the unravelling of the physiopathology of the human disease.

Osteoarthritis; Pain; Mono-iodoacetate; ATF-3; NPY; GAP-43; Neuronal injury