ATP and glutamate (Glu) are known to be released into the extracellular space through pannexin 1 (Panx1) channels in the cell membrane. Neuronal Panx1 contributes to the development and maintenance of peripheral inflammation-induced tactile hypersensitivity. In order to study mechanisms of orofacial neuropathic pain, we analyzed the role of Panx1 in the trigeminal ganglion (TG) of rats with infraorbital nerve injury (IONI). Male SD rats were used. We measured mechanical head-withdrawal threshold (MHWT) in IONI rats receiving an intra-TG Panx1 inhibitor or a metabotropic Glu receptor 5 (mGluR5) antagonist and in naive rats receiving intra-TG mGluR5 agonist administration post-IONI. Glu and Panx1 in TG were measured post-IONI. Panx1, mGluR5 and Glu synthetase expression in TG were analyzed immunohistochemically and changes in the number of mGluR5-P2X₃-expressed TG neurons were evaluated. MHWT was decreased after IONI and this decrease was reversed by the Panx1 inhibitor and the mGluR5 antagonist. The mGluR5 agonist decreased MHWT. IONI increased extracellular Glu in TG. Panx1 was expressed in satellite glial cells and TG neurons, and intra-TG mGluR5 antagonism decreased the number of mGluR5- and P2X₃-positive TG neurons post-IONI. The present results indicate that IONI facilitates Glu release via Panx1 that activates mGluR5 expressed in nociceptive TG neurons innervating the orofacial region. In turn, P2X₃ receptor-expressed TG neurons are enhanced via mGluR5 signaling, resulting in orofacial neuropathic pain.