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KMID : 1040020190100010001
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International Journal of Pain
2019 Volume.10 No. 1 p.1 ~ p.9
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Dexmedetomidine Inhibits Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channels Currents in Trigeminal Ganglion Neurons
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Lee Ki-Hwan
Im Sang-Taek
Kim Yong-Ho
Park Chul-Kyu
Chung Ge-Hoon
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Abstract
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Dexmedetomidine (DEX), an α2-adrenergic receptor agonist, is widely used as a sedative and an analgesic agent in many clinical applications. However, little is known about the molecular mechanisms responsible for its analgesic properties in the trigeminal system. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles in mediating inflammatory and neuropathic pain by modulating neuronal excitability. To elucidate the molecular mechanism underlying the analgesic action of dexmedetomidine, we investigated the effect of dexmedetomidine on HCN currents (Ih) in acutely dissociated medium- and large-sized trigeminal ganglion (TG) neurons using a whole-cell patch-clamp recording. Dexmedetomidine showed a dose-dependent inhibition of Ih in medium- and large-sized TG neurons. RT-PCR analysis revealed mRNAs for Hcn1 and Hcn2 channels and α2-adrenergic receptors (Adra2a) in murine TG neurons. The inhibition of Ih by dexmedetomidine was partially reversed by yohimbine, a competitive ADRA2A antagonist, and guanosine 5′-[β-thio] diphosphate trilithium salt (GDPβS), a non-hydrolyzing analogue of GDP. These results suggest that dexmedetomidine inhibits Ih through activation of Gi/o-protein coupled Adra2a in the trigeminal system.
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KEYWORD
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HCN, dexmedetomidine, pain, adrenergic, analgesic, hyperalgesia
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