Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons
Dexmedetomidine, an α2-adrenoceptor agonist, is widely used as a sedative and analgesic agent in a number of clinical applications. However, little is known about the mechanism by which it exerts its analgesic effects on the trigeminal system. Two types of voltage-gated sodium channels, Nav1.7 and N...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/1782719 |
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| author | Sang-Taek Im Youn Yi Jo Gayoung Han Hyun Jung Jo Yong Ho Kim Chul-Kyu Park |
| author_facet | Sang-Taek Im Youn Yi Jo Gayoung Han Hyun Jung Jo Yong Ho Kim Chul-Kyu Park |
| author_sort | Sang-Taek Im |
| collection | DOAJ |
| description | Dexmedetomidine, an α2-adrenoceptor agonist, is widely used as a sedative and analgesic agent in a number of clinical applications. However, little is known about the mechanism by which it exerts its analgesic effects on the trigeminal system. Two types of voltage-gated sodium channels, Nav1.7 and Nav1.8, as well as α2-adrenoceptors are expressed in primary sensory neurons of the trigeminal ganglion (TG). Using whole-cell patch-clamp recordings, we investigated the effects of dexmedetomidine on voltage-gated sodium channel currents (INa) via α2-adrenoceptors in dissociated, small-sized TG neurons. Dexmedetomidine caused a concentration-dependent inhibition of INa in small-sized TG neurons. INa inhibition by dexmedetomidine was blocked by yohimbine, a competitive α2-adrenoceptor antagonist. Dexmedetomidine-induced inhibition of INa was mediated by G protein-coupled receptors (GPCRs) as this effect was blocked by intracellular perfusion with the G protein inhibitor GDPβ-S. Our results suggest that the INa inhibition in small-sized TG neurons, mediated by the activation of Gi/o protein-coupled α2-adrenoceptors, might contribute to the analgesic effects of dexmedetomidine in the trigeminal system. Therefore, these new findings highlight a potential novel target for analgesic drugs in the orofacial region. |
| format | Article |
| id | doaj-art-577b0584396d485a9885b165b4f91c75 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-577b0584396d485a9885b165b4f91c752025-02-03T06:12:23ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/17827191782719Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion NeuronsSang-Taek Im0Youn Yi Jo1Gayoung Han2Hyun Jung Jo3Yong Ho Kim4Chul-Kyu Park5Gachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of KoreaDepartment of Anesthesiology and Pain Medicine, Gachon University, Gil Medical Center, Incheon 21565, Republic of KoreaCollege of Art & Design, Kyung Hee University, Yongin 17104, Republic of KoreaGachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of KoreaGachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of KoreaGachon Pain Center and Department of Physiology, College of Medicine, Gachon University, Incheon 21999, Republic of KoreaDexmedetomidine, an α2-adrenoceptor agonist, is widely used as a sedative and analgesic agent in a number of clinical applications. However, little is known about the mechanism by which it exerts its analgesic effects on the trigeminal system. Two types of voltage-gated sodium channels, Nav1.7 and Nav1.8, as well as α2-adrenoceptors are expressed in primary sensory neurons of the trigeminal ganglion (TG). Using whole-cell patch-clamp recordings, we investigated the effects of dexmedetomidine on voltage-gated sodium channel currents (INa) via α2-adrenoceptors in dissociated, small-sized TG neurons. Dexmedetomidine caused a concentration-dependent inhibition of INa in small-sized TG neurons. INa inhibition by dexmedetomidine was blocked by yohimbine, a competitive α2-adrenoceptor antagonist. Dexmedetomidine-induced inhibition of INa was mediated by G protein-coupled receptors (GPCRs) as this effect was blocked by intracellular perfusion with the G protein inhibitor GDPβ-S. Our results suggest that the INa inhibition in small-sized TG neurons, mediated by the activation of Gi/o protein-coupled α2-adrenoceptors, might contribute to the analgesic effects of dexmedetomidine in the trigeminal system. Therefore, these new findings highlight a potential novel target for analgesic drugs in the orofacial region.http://dx.doi.org/10.1155/2018/1782719 |
| spellingShingle | Sang-Taek Im Youn Yi Jo Gayoung Han Hyun Jung Jo Yong Ho Kim Chul-Kyu Park Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons Mediators of Inflammation |
| title | Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons |
| title_full | Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons |
| title_fullStr | Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons |
| title_full_unstemmed | Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons |
| title_short | Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons |
| title_sort | dexmedetomidine inhibits voltage gated sodium channels via α2 adrenoceptors in trigeminal ganglion neurons |
| url | http://dx.doi.org/10.1155/2018/1782719 |
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