Glial activation in the rostroventromedial medulla promotes descending facilitation to mediate inflammatory hypersensitivity

Substantial evidence shows that activation of glial cells in the spinal cord may promote central sensitization and pain. Descending facilitation from the rostroventromedial medulla (RVM) is a critical component in the maintenance of chronic pain states, although the precise mechanisms through which facilitation maintains pain are unclear. Here, we investigated the possibility that glial activation in the RVM could promote descending facilitation from the RVM in states of inflammatory pain. Peripheral inflammation was induced with carrageenan injected into the hindpaws of male Sprague-Dawley rats, and behavioral responses to noxious thermal and light tactile stimuli were determined. Microinjection of the glial inhibitors minocycline or fluorocitrate, or of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580, produced a significant and time-related attenuation of behavioral hypersensitivity resulting from hindpaw inflammation. Carrageenan-induced inflammation increased immunolabeling for microglia and astrocytes in the RVM, as well as for phosphorylated p38 MAPK. Phosphorylated p38 MAPK was found in microglia and neurons of the RVM. Inflammation-induced microglial and astrocytic activation in the RVM were attenuated by RVM microinjection of the glial inhibitors. The data show that inflammatory pain is associated with glial activation in the RVM that probably participates in driving descending pain facilitation. These findings reveal a novel site of glial modulation of inflammatory pain.