Immunohistochemical comparison of astrocytic mGluR5 upregulation in infraorbital nerve- versus sciatic nerve-ligated rat.

The differential pharmacological responsiveness of cephalic and extra-cephalic neuropathic pain has been proposed to relate to distinct mechanisms that may involve neuroinflammatory reactions mediated by glial cells. Astrocytes are particularly important for neuronal sensitization in neuropathic pain, in part through modulation of glutamatergic transmission. Because the metabotropic glutamate receptor 5 (mGluR5) is involved in the astrocytic regulation of the glutamatergic system, we investigated modifications of its expression in models of cephalic versus extra-cephalic neuropathic pain. Adult male rats underwent unilateral chronic constriction injury (CCI) of either the infraorbital nerve (ION) or the sciatic nerve (SN). Seven days later, mGluR5 and the astrocyte marker GFAP (glial fibrillary acidic protein) were overexpressed and appeared localized mainly in the superficial lamina of the trigeminal nucleus in CCI-ION and the spinal cord dorsal horn in CCI-SN rats. In addition, colocalization of GFAP and mGluR5 strongly suggested an increase of astrocytic mGluR5 expression in nerve-injured rats compared to sham animals. The present data show an upregulation of astrocytic mGluR5 in central structures in both CCI-ION and CCI-SN. This suggests that the pharmacological modulation of mGluR5 could be a new approach to reduce both cephalic and extra-cephalic neuropathic pain.