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Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain.
J Pain. 2018 06; 19(6):626-634.JP

Abstract

Orofacial 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.

PERSPECTIVE

Trigeminal 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.

Authors+Show Affiliations

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.MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.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.MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: jmao@mgh.harvard.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29366880

Citation

Ding, Weihua, et al. "Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain." The Journal of Pain, vol. 19, no. 6, 2018, pp. 626-634.
Ding W, You Z, Shen S, et al. Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain. J Pain. 2018;19(6):626-634.
Ding, W., You, Z., Shen, S., Yang, J., Lim, G., Doheny, J. T., Zhu, S., Zhang, Y., Chen, L., & Mao, J. (2018). Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain. The Journal of Pain, 19(6), 626-634. https://doi.org/10.1016/j.jpain.2018.01.003
Ding W, et al. Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain. J Pain. 2018;19(6):626-634. PubMed PMID: 29366880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain. AU - Ding,Weihua, AU - You,Zerong, AU - Shen,Shiqian, AU - Yang,Jinsheng, AU - Lim,Grewo, AU - Doheny,Jason T, AU - Zhu,Shengmei, AU - Zhang,Yi, AU - Chen,Lucy, AU - Mao,Jianren, Y1 - 2018/01/31/ PY - 2017/09/28/received PY - 2017/12/15/revised PY - 2018/01/03/accepted PY - 2018/1/26/pubmed PY - 2019/11/12/medline PY - 2018/1/26/entrez KW - Gasserian ganglion KW - Trigeminal neuropathic pain KW - ZD7288 KW - hyperpolarization-activated cyclic nucleotide-gated channel KW - ivabradine SP - 626 EP - 634 JF - The journal of pain JO - J Pain VL - 19 IS - 6 N2 - : Orofacial 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. PERSPECTIVE: Trigeminal 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. SN - 1528-8447 UR - https://www.unboundmedicine.com/medline/citation/29366880/Increased_HCN_Channel_Activity_in_the_Gasserian_Ganglion_Contributes_to_Trigeminal_Neuropathic_Pain_ DB - PRIME DP - Unbound Medicine ER -