• Weihua Ding, Zerong You, Shiqian Shen, Jinsheng Yang, Grewo Lim, Jason T Doheny, Shengmei Zhu, Yi Zhang, Lucy Chen, and Jianren Mao.
• MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; The First Affiliated Hospital of Zhejiang University, Hangzhou, China.
• J Pain. 2018 Jun 1; 19 (6): 626634626-634.

UnlabelledOrofacial neuropathic pain caused by trigeminal nerve injury is a debilitating condition with limited therapeutic options. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability and are involved in the development and maintenance of chronic pain. However, the effect of HCN channel activity in the Gasserian ganglion on trigeminal neuropathic pain has not been examined. We evaluated nociceptive behaviors after microinjection of the HCN channel blockers ZD7288 or ivabradine into the Gasserian ganglion in rats with trigeminal nerve injury. Both blockers dose-dependently ameliorated evoked and spontaneous nociceptive behavior in rats with trigeminal neuropathic pain. Moreover, the clinically available HCN channel blocker ivabradine showed a prolonged antinociceptive effect. In the Gasserian ganglion, HCN1 and HCN2 are major HCN isoforms. After trigeminal nerve injury, the counts of HCN1 as well as HCN2 immuno-positive punctae were increased in the ipsilateral Gasserian ganglions. These results indicate that the increased HCN channel activity in the Gasserian ganglion directly contributes to neuropathic pain resulting from trigeminal nerve injury.PerspectiveTrigeminal nerve damage-induced orofacial pain is severe and more resistant to standard pharmacological treatment than other types of neuropathic pain. Our study suggests that targeting HCN channel activities in the Gasserian ganglion may provide an alternative treatment of trigeminal neuropathy including trigeminal neuralgia.Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

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