Background Pain is the most distressing feature of osteoarthritis (OA), but its treatment remains highly ineffective. The mechanisms of OA-associated pain are far from being fully understood which might impair the discovery of new more efficient therapeutic solutions. Therefore, studies on the neurobiological mechanisms of pain associated with OA are of utmost importance, and animal models are crucial and relevant tools to perform those studies. Previous findings on OA models have shown that injury of primary afferent neurons may be coupled to the development of nociception associated with OA1,2.
Objectives Since the activation of satellite glial cells (SGC) surrounding primary afferent neurons has also been described to occur after peripheral nerve injury and to contribute to the maintenance of neuropathic pain3, we evaluated the expression of the glial fibrillary acidic protein (GFAP), a marker of SGC activation, in the dorsal root ganglia (DRG) of rats with OA. Furthermore, to assess SGC activation around injured neurons, a co-localization analysis of ATF-3 and GFAP expression was performed, since ATF-3 is a widely accepted neuronal injury marker4.
Methods The collagenase model of OA was used in this study. OA was induced by injection of 500U of type II collagenase into the knee joint of rats, at days 0 and 3. Movement-induced nociception was evaluated weekly, until sacrifice, by the Knee-Bend and CatWalk tests. Animals were sacrificed 6 weeks after the first collagenase injection (n=6/group). L3-L5 DRGs were used for immunodetection of GFAP or GFAP plus ATF-3 and knee joints were processed for histopathological evaluation.
Results OA animals showed an increase in movement-induced nociception when evaluated by both the Knee-Bend and Catwalk tests. Histopathological changes observed after 6 weeks of OA induction were very similar to those described in clinical OA, leading to extensive cartilage degeneration with fissures and exposure of the subchondral bone. GFAP expression in the SGC of OA animals was significantly increased when compared to control animals and a correlation between satellite glial cell activation and the degree of histological damage was observed. Co-localization analysis of ATF-3 and GFAP expression showed a significant increase in the proportion of GFAP-encircled neurons within the ATF-3 immunoreactive population. However, the majority of ATF-3 positive neurons were not surrounded by GFAP-positive SGC, and the majority of activated SGC were located around uninjured neurons.
Conclusions SGC activation was observed in the collagenase model of OA, although it was not restricted to injured neurons. This SGC reactive change may be implicated in the development and/or maintenance of pain in this OA model.
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Acknowledgements Granted by a Calouste Gulbenkian Foundation PhD scholarship and FCT (PTDC/SAU-NSC/119986/2010).
Disclosure of Interest : None declared