日韓シンポジウム

[JK-02] The pivotal role of neuron-glia interaction in persistent orofacial pain

〇Koichi Iwata¹, Yoshinori Hayashi¹, Suzuro Hitomi¹, Yosuke Ikehata¹, Masamichi Shinoda¹ (1. Dept Physiol, Nihon Univ Sch Dent)

キーワード：trigeminal nerve、persistent pain、glia

It is well known that trigeminal nerve injury frequently occurs following surgical procedures in the orofacial regions, such as tooth extraction or dental implantation, and chronic orofacial inflammation is caused by pulpitis or periodontitis. In addition, trigeminal nerve injury or orofacial inflammation sometimes causes persistent orofacial pain. However, detailed mechanisms underlying persistent orofacial pain associated with trigeminal nerve injury or orofacial inflammation are not thoroughly elucidated. The neuron-glia interaction within the trigeminal ganglion (TG) and the trigeminal spinal subnucleus caudalis (Vc) is thought to be one of the possible mechanisms for the persistent orofacial pain associated with trigeminal nerve injury or orofacial inflammation. Following trigeminal nerve injury or inflammation, the injured neurons or neurons innervating the inflamed region become hyperactive. The various cytokines, such as IL-1, TNFa, IFNg, neuropeptides, or nitric oxide, are released from neurons and/or glial cells, and those molecules contribute to neuron-glia communication in TG and the Vc. We recently observed that the IL-33 expression was increased in oligodendrocytes in the Vc following infraorbital nerve injury. Neutralizing the IL-33 receptor in Vc relieved mechanical hypersensitivity associated with infraorbital nerve injury. We also found that the IL-33 expression in the TG was significantly enhanced after infraorbital nerve injury. The immunohistochemical study revealed that IL-33 was expressed in αSMA or CD34 (fibroblast marker) immunoreactive cells, and IL-33 receptor was expressed in TG neurons in trigeminal-nerve injured mice, suggesting that the IL-33 released from fibroblasts after the nerve injury was involved in the hyperactivation of TG neurons. We also observed that intra-TG administration of IL-33 caused mechanical hypersensitivity in the whisker pad skin. These results suggest that IL-33 released from oligodendrocytes causes the enhancement of Vc neuronal activity, and IL-33 released from fibroblasts in TG also causes increased TG-neuronal activity, resulting in persistent orofacial pain following infraorbital nerve injury. In this symposium, we address our current results regarding mechanisms of neuro-glia interaction following trigeminal nerve injury or orofacial inflammation and discuss its contribution to persistent orofacial pain.