Central and peripheral effects of environmental enrichment in a mouse model of arthritis

This study analyzed whether environmental enrichment (EE) modulates the nociceptive and inflammatory responses in the mouse model of arthritis induced by Complete Freund's Adjuvant (CFA). Ninety male mice (C57BL/6-JUnib, 4-weeks-old; 20-25 g) were distributed into EE and standard (SE) groups. For EE, mice were kept in bigger cages using an alternation of materials to chew (wood and paper), for nesting (cotton), to use as hiding places (plastic tunnels), and for voluntary exercise (wheel running). Arthritis was induced by an injection of CFA (50 μL) into the right hind paw or saline solution in the control group. Separate groups received the anti-inflammatory drug dexamethasone (0.5 mg/kg; every 48 h). Inflammatory and pain measurements were performed from 1 to 35 days after CFA administration. EE per se reduced the acute paw edema formation and arthritis scores. The serum levels of tumor necrosis factor (TNF) were undetectable in any experimental groups. EE diminished the immunopositivity for the microglia marker IBA1 in the pre-frontal cortex, with slight changes for hippocampal GFAP-positive activated astrocytes. Finally, EE induced a marked increment of brain-derived nerve factor (BDNF) expression in the hippocampus, an effect that was fully prevented by dexamethasone. These data bring novel evidence on the peripheral and central effects of EE in a mouse arthritis model.