Effects of restraint stress on glial activity in the rostral ventromedial medulla

Stress affects brain activity and promotes long-term changes in multiple neural systems. Exposure to stressors causes substantial effects on the perception and response to pain. In several animal models, chronic stress produces lasting hyperalgesia. Postmortem studies of patients with stress-related psychiatric disorders have demonstrated a decrease in the number of astrocytes and the level of glial fibrillary acidic protein (GFAP), a marker for astrocyte, in the cerebral cortex. Since astrocytes play vital roles in maintaining neuroplasticity via synapse maintenance and secretion of neurotrophins, damage of astrocytes is thought to be involved in the neuropathology. In the present study we examined GFAP, S100β and CD11b protein levels in the rostral ventromedial medulla (RVM) after the subacute and chronic restraint stresses to clarify changes in descending pain modulatory system in the rat with stress-induced hyperalgesia. Chronic restraint stress (6h/day for 3 weeks), but not subacute restraint stress (6h/day for 3 days), caused a marked mechanical hypersensitivity. Subacute and chronic restraint stresses induced a significant decrease of GFAP protein level in the RVM (21.9 ± 3.6%, p<0.01 and 18.2 ± 5.1%, p<0.05 vs. control group, respectively). In the chronic stress group, the GFAP protein level in the RVM was positively correlated with the mechanical threshold (p<0.05). The immunohistochemical analysis revealed that chronic restraint stress induced a significant decrease in GFAP-immunoreactivity in the nucleus raphe magnus, a part of the RVM, compared to subacute restraint stress. In contrast there was no significant difference in the S100β and CD11b protein levels between the control and stress groups. These findings suggest that the long-lasting decrease of GFAP protein induced by chronic restraint stress causes dysfunction of astrocytes, which may be involved in the impairment of the RVM that plays pivotal roles in pain modulation.