It is well known that the trigeminal nerve injury such as tooth extraction or pulpectomy sometime causes severe pain (neuropathic pain) in the orofacial regions. The orofacial neuropathic pain caused by trigeminal nerve injury is difficult to diagnose and treat because of the complexity of its neuronal mechanism. It is very important to evaluate the neuronal mechanisms underlying orofacial neuropathic pain, in order to develop the appropriate approaches to treat neuropathic pain patients. For this purpose, we developed the rats model with trigeminal nerve injury (inferior alveolar transection: IANX) in which mechanical allodynia and hyperalgesia occurred in the whisker pad skin. Recently, it has been reported that the sciatic nerve injury causes a down-regulation of potassium-chloride exporter KCC2 in the spinal dorsal horn neurons, contributing to the development of neuropathic pain in the foot.
　We hypothesized that down-regulation of GABA transporter might be involved in an increase in the excitability of the trigeminal subnucleus caudalis (Vc) neurons after IANX, involving in the development of orofacial neuropathic pain in the whisker pad skin. For this purpose we introduced, VGAT-Venus A (VA) expressing rats which coexpressed fluorescent protein and the vesicular GABA transporter in the Vc neurons to analyze the functional changes in GABAergic neurons in the Vc, and mechanical nocifensive behavior, KCC2 immunohistochemistry and single neuron activity were precisely analyzed in the rats with IANX at 21 days after IAN transection.
　Head-withdrawal threshold to mechanical stimulation of the whisker pad skin significantly decreased in IANX-rats 7 and 21 days after IAN transection. Majority of KCC2 positive VA neurons was significantly decreased in IANX rats 21 days after IAN transection. The neuronal excitability of Vc nociceptive neurons was enhanced after intrathecal administration of R-DIOA in the Sham rats.
　These findings revealed that the functional change from inhibitory to excitatory might be induced in GABAergic interneurons after IANX, suggesting that the neuroplastic change in the GABAergic neuronal network in the Vc is involved in the trigeminal neuropathic pain after IANX.