Satellite glial cells surrounding primary afferent neurons are activated and proliferate during monoarthritis in rats: is there a role for ATF3?

• Published in: PloS one 2014-09, Vol.9 (9), p.e108152-e108152
• Main Authors: Nascimento, Diana Sofia Marques, Castro-Lopes, José Manuel, Moreira Neto, Fani Lourença
• Format: Article
• Language: English
• Subjects: Activating transcription factor 3; Activating Transcription Factor 3 - metabolism; Activation; Animals; Ankle; Arthritis; Arthritis, Experimental - metabolism; Arthritis, Experimental - physiopathology; Biology and Life Sciences; Cell Proliferation - physiology; Chronic pain; Communication; Disease control; Dorsal root ganglia; Freund's adjuvant; Ganglia; Ganglia, Spinal - metabolism; Glial cells; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - metabolism; Health aspects; Hypertrophy; Inflammation; Inflammatory diseases; Injuries; Intermediate filament proteins; Labeling; Labelling; Male; Morphology; Nervous system; Neuronal-glial interactions; Neurons; Neurons, Afferent - metabolism; Neurophysiology; Pain; Proteins; Rats; Rodents; Satellite Cells, Perineuronal - metabolism; Sensory neurons; Studies; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0108152

Joint inflammatory diseases are debilitating and very painful conditions that still lack effective treatments. Recently, glial cells were shown to be crucial for the development and maintenance of chronic pain, constituting novel targets for therapeutic approaches. At the periphery, the satellite glial cells (SGCs) that surround the cell bodies of primary afferents neurons in the dorsal root ganglia (DRG) display hypertrophy, proliferation, and activation following injury and/or inflammation. It has been suggested that the expression of neuronal injury factors might initially trigger these SGCs-related events. We then aimed at evaluating if SGCs are involved in the establishment/maintenance of articular inflammatory pain, by using the monoarthritis (MA) model, and if the neuronal injury marker activating transcriptional factor 3 (ATF3) is associated with these SGCs' reactive changes. Western Blot (WB) analysis of the glial fibrillary acidic protein (GFAP) expression was performed in L4-L5 DRGs from control non-inflamed rats and MA animals at different time-points of disease (4, 7, and 14d, induced by complete Freund's adjuvant injection into the left hind paw ankle joint). Data indicate that SGCs activation is occurring in MA animals, particularly after day 7 of disease evolution. Additionally, double-immunostaining for ATF3 and GFAP in L5 DRG sections shows that SGCs's activation significantly increases around stressed neurons at 7d of disease, when compared with control animals. The specific labelling of GFAP in SGCs rather than in other cell types was also confirmed by immunohistochemical labeling. Finally, BrdU incorporation indicates that proliferation of SGCs is also significantly increased after 7 days of MA. Data indicate that SGCs play an important role in the mechanisms of articular inflammation, with 7 days of disease being a critical time-point in the MA model, and suggest that ATF3 might be involved in SGCs' reactive changes such as activation.