Purinergic Receptor- and Metabotropic Glutamate Receptor 5-Mediated Interactions Between Satellite Glial Cells and...

Activation of satellite glial cells (SGCs) within the dorsal root ganglia and trigeminal ganglia (TG) has been reported to be involved in pain associated with peripheral neuropathy. One of the activation mechanisms of SGCs is that adenosine triphosphate (ATP) released from ganglion neurons transmits information via the purinergic receptor 7 (P2X₇-R) expressed on SGCs. However, it remains unknown whether primary nociceptive neurons change their excitability following activation of the ATP-P2X₇-R pathway. In the present study, excitatory changes in TG neurons following P2X₇-R-mediated SGCs activation were analyzed using whole-cell patch-clamp recordings with whole-mounted or sliced TG preparations from Sprague-Dawley rats. When the P2X₇-R agonist BzATP was applied instead of ATP, the minimum current amplitude required to induce an action potential in TG neurons was significantly reduced compared with that in the vehicle-treated group. No neuronal excitability changes were induced by BzATP in the presence of the selective P2X₇-R antagonist A740003, the metabotropic glutamate receptor 5 (mGluR5) inhibitor MTEP, or the hemichannel inhibitor carbenoxolone. Immunofluorescence examination revealed that P2X₇-R was localized in SGCs, and mGluR5 was localized in TG neurons. We confirmed that primary cultured SGCs released glutamate following BzATP stimulation. These results indicate that glutamate released from SGCs via hemichannels in a paracrine manner may alter the excitability of neighboring TG neurons. Following activation of SGCs, we analyzed the excitatory changes occurring in neurons using patch-clamp recording in intact TG preparations, and, for the first time, identified that glutamate released from SGCs activates mGluR5 on neurons, contributing to these excitatory changes.