Dose-Dependent Expression of Neuronal Injury Markers during Experimental Osteoarthritis Induced by Monoiodoacetate in the Rat

Author:

Ferreira-Gomes Joana1,Adães Sara1,Sousa Raquel Meireles1,Mendonça Marcelo1,Castro-Lopes José Manuel1

Affiliation:

1. 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

Abstract

Background: 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. Results: 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. Conclusions: 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.

Publisher

SAGE Publications

Subject

Anesthesiology and Pain Medicine,Cellular and Molecular Neuroscience,Molecular Medicine

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