Dexmedetomidine and clonidine inhibit the function of NaV1.7 independent of α2-adrenoceptor in adrenal chromaffin cells

Maruta, Toyoaki; Nemoto, Takayuki; Satoh, Shinya; Kanai, Takahiro; Yanagita, Toshihiko; Wada, Akihiko; Tsuneyoshi, Isao

doi:10.1007/s00540-011-1168-6

Cited by 19 publications

(18 citation statements)

References 45 publications

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“…Moreover, it was reported that the α 2-adrenoceptor was expressed by more than 60% of neurons in the TG and over 80% of neurons in the DRG [ 5 , 6 ]. Recent studies demonstrate the antinociceptive mechanism of dexmedetomidine in the somatosensory system, specifically at the spinal cord and peripheral nervous system [ 8 , 19 , 20 , 25 ]. Several studies specifically targeted ion channels (VGSCs, hyperpolarization-activated cyclic nucleotide-gated channels) in the dorsal root ganglion that are primarily related to nociception.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies specifically targeted ion channels (VGSCs, hyperpolarization-activated cyclic nucleotide-gated channels) in the dorsal root ganglion that are primarily related to nociception. These studies show that the mechanism of action of dexmedetomidine is related to the suppression of these channels [ 8 , 19 , 20 , 26 ]. This suggests that dexmedetomidine blocks pain in the somatic system at the level of the peripheral nervous system.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have revealed that dexmedetomidine inhibits both tetrodotoxin-resistant and tetrodotoxin-sensitive sodium channels in DRG neurons [ 8 , 19 , 20 ]. However, it remains unclear whether dexmedetomidine can inhibit the function of VGSCs in neurons of the trigeminal system.…”

Section: Introductionmentioning

confidence: 99%

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Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons

Han

et al. 2018

Mediators of Inflammation

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons

Han

et al. 2018

Mediators of Inflammation

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“…Blocking the I h current will result in prolonged hyperpolarization of the nerve, which seems to be more distinct in the unmyelinated C (i.e., pain) fibers than in α (i.e., motor) fibers. Furthermore, Maruta found that dexmedetomidine can inhibit the function of Na(v)1.7, independent of α-2-adrenoceptor in adrenal chromaffin cells [ 28 ]. This effect could not be prevented by a perfused α-2-receptor antagonist, which may imply the mechanism of the peripheral antinociceptive effects of α-2-agonists [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Perineural Dexmedetomidine as an Adjuvant Reduces the Median Effective Concentration of Lidocaine for Obturator Nerve Blocking: A Double-Blinded Randomized Controlled Trial

Sun

Zhuang

et al. 2016

PLoS ONE

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Research suggests that the addition of dexmedetomidine to local anesthetics can prolong peripheral nerve blocks; however, it is not known whether dexmedetomidine can reduce the quantity of local anesthetic needed. We hypothesized that adding dexmedetomidine as an adjuvant to an obturator nerve block could reduce the median effective concentration of lidocaine. In this double-blinded randomized trial, 60 patients scheduled for elective transurethral resection of bladder tumors on the lateral wall were randomly divided into two groups: the control group (C group, n = 30) and the dexmedetomidine group (D group, n = 30). Two main branches of the obturator nerve (i.e., anterior and posterior) were identified using neural stimulation at the inguinal level, with only lidocaine used for the C group and 1 μg/kg dexmedetomidine combined with lidocaine used for the D group. The median effective concentration was determined by an up-and-down sequential trial. The ratio of two consecutive concentrations was 1.2. The median effective concentration (95% confidence interval) of lidocaine was 0.57% (0.54%-0.62%) in the C group and 0.29% (0.28%-0.38%) in the D group. The median effective concentration of lidocaine was significantly lower in the D group than in the C group (p < 0.05). These results indicate that dexmedetomidine (1 μg/kg) in combination with lidocaine for obturator nerve block decreases the median effective concentration of lidocaine.Trial Registration: ClinicalTrials.gov NCT02066727

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“…But the newly performed studies have claimed that the peripheral and neuraxial effects of clonidine may have some different mechanism of action rather than the previously demonstrated role of clonidine as an alpha 2 adrenoceptor agonist. Though the exact mechanism is not clear, some hypothetical mechanisms have been proposed and a number of them like the role of clonidine in inhibition of tetrodotoxin-sensitive sodium channels have been demonstrated ( 10 ). Much more similar studies like the latter one are in process.…”

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confidence: 99%

Clonidine: an old friend newly rediscovered

Dabbagh

2011

Anesth Pain

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Dexmedetomidine and clonidine inhibit the function of NaV1.7 independent of α2-adrenoceptor in adrenal chromaffin cells

Abstract: Dexmedetomidine and clonidine inhibit the function of Na(v)1.7 independent of α(2)-adrenoceptor. These results may lead to a deeper understanding of the peripheral antinociceptive effects of α (2)-agonists.

Cited by 19 publications

References 45 publications

Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons

Dexmedetomidine Inhibits Voltage-Gated Sodium Channels via α2-Adrenoceptors in Trigeminal Ganglion Neurons

Perineural Dexmedetomidine as an Adjuvant Reduces the Median Effective Concentration of Lidocaine for Obturator Nerve Blocking: A Double-Blinded Randomized Controlled Trial

Clonidine: an old friend newly rediscovered

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