Effects of WIN55,212-2 on voltage-gated sodium channels in trigeminal ganglion neurons of rats

2008 ◽  
Vol 30 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Hui Fu ◽  
Jian Min Xiao ◽  
Xue Hong Cao ◽  
Zhang Yin Ming ◽  
Lie Ju Liu
Keyword(s):  
Sodium Channels ◽  
Trigeminal Ganglion ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Trigeminal Ganglion Neurons ◽  
Ganglion Neurons

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

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Sang-Taek Im ◽  
Youn Yi Jo ◽  
Gayoung Han ◽  
Hyun Jung Jo ◽  
Yong Ho Kim ◽  
...  
Keyword(s):  
G Protein ◽  
Sodium Channels ◽  
Trigeminal Ganglion ◽  
Trigeminal System ◽  
Voltage Gated ◽  
Analgesic Effects ◽  
Voltage Gated Sodium Channels ◽  
New Findings ◽  
Orofacial Region ◽  
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 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.

scholarly journals Co-Application of Eugenol and QX-314 Elicits the Prolonged Blockade of Voltage-Gated Sodium Channels in Nociceptive Trigeminal Ganglion Neurons

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1513
Author(s):  
Sung-Min Hwang ◽  
Kihwan Lee ◽  
Sang-Taek Im ◽  
Eun Jin Go ◽  
Yong Ho Kim ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Trigeminal Ganglion ◽  
Transient Receptor Potential ◽  
Pain Treatment ◽  
Transient Receptor Potential Vanilloid ◽  
Dependent Manner ◽  
Noxious Heat ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Ganglion Neurons

Local anesthetics (LAs) can completely block nociception by inhibiting voltage-gated sodium channels (VGSCs), and thus, blocking action potentials (APs) within sensory neurons. As one of the several LAs, eugenol is used for dental pain treatment. It reportedly features multiple functions in regulating diverse ion channels. This study aimed to investigate the long-lasting analgesic effect of eugenol alone, as well as that of the combination of eugenol as a noxious-heat-sensitive transient receptor potential vanilloid 1 (TRPV1) channel agonist and a permanently charged sodium channel blocker (QX-314), on neuronal excitability in trigeminal ganglion (TG) neurons. Eugenol alone increased inward current in a dose-dependent manner in capsaicin-sensitive TG neurons. Eugenol also inhibited the VGSC current and AP. These effects were reversed through wash-out. The combination of eugenol and QX-314 was evaluated in the same manner. The combination completely inhibited the VGSC current and AP. However, these effects were not reversed and were continuously blocked even after wash-out. Taken together, our results suggest that, in contrast to the effect of eugenol alone, the combination of eugenol and QX-314 irreversibly and selectively blocked VGSCs in TG neurons expressing TRPV1.

Capsaicin Inhibits Activation of Voltage-Gated Sodium Currents in Capsaicin-Sensitive Trigeminal Ganglion Neurons

2001 ◽  
Vol 85 (2) ◽  
pp. 745-758 ◽  
Author(s):  
L. Liu ◽  
M. Oortgiesen ◽  
L. Li ◽  
S. A. Simon
Keyword(s):  
Trigeminal Ganglion ◽  
Second Messengers ◽  
Receptor Activation ◽  
Hot Pepper ◽  
Capsaicin Receptor ◽  
Voltage Gated ◽  
Analgesic Effects ◽  
Voltage Gated Sodium Channels ◽  
Camp Generation ◽  
Ganglion Neurons

Capsaicin, the pungent ingredient in hot pepper, activates nociceptors to produce pain and inflammation. However, repeated exposures of capsaicin will cause desensitization to nociceptive stimuli. In cultured trigeminal ganglion (TG) neurons, we investigated mechanisms underlying capsaicin-mediated inhibition of action potentials (APs) and modulation of voltage-gated sodium channels (VGSCs). Capsaicin (1 μM) inhibited APs and VGSCs only in capsaicin-sensitive neurons. Repeated applications of capsaicin produced depolarizing potentials but failed to evoke APs. The capsaicin-induced inhibition of VGSCs was prevented by preexposing the capsaicin receptor antagonist, capsazepine (CPZ). The magnitude of the capsaicin-induced inhibition of VGSCs was dose dependent, having a K 1/2 = 0.45 μM. The magnitude of the inhibition of VGSCs was proportional to the capsaicin induced current (for – I CAP < 0.2 nA). Capsaicin inhibited activation of VGSCs without changing the voltage dependence of activation or markedly changing channel inactivation and use-dependent block. To explore the changes leading to this inhibition, it was found that capsaicin increased cAMP with a K 1/2 = 0.18 μM. At 1 μM capsaicin, this cAMP generation was inhibited 64% by10 μM CPZ, suggesting that activation of capsaicin receptors increased cAMP. The addition of 100 μM CPT-cAMP increased the capsaicin-activated currents but inhibited the VGSCs in both capsaicin-sensitive and -insensitive neurons. In summary, the inhibitory effects of capsaicin on VGSCs and the generation of APs are mediated by activation of capsaicin receptors. The capsaicin-induced activation of second messengers, such as cAMP, play a part in this modulation. These data distinguish two pathways by which neuronal sensitivity can be diminished by capsaicin: by modulation of the capsaicin receptor sensitivity, since the block of VGSCs is proportional to the magnitude of the capsaicin-evoked currents, and by modulation of VGSCs through second messengers elevated by capsaicin receptor activation. These mechanisms are likely to be important in understanding the analgesic effects of capsaicin.

Ethanol inhibits voltage-gated sodium channels in cultured superior cervical ganglion neurons

Neuroreport ◽  
2008 ◽  
Vol 19 (18) ◽  
pp. 1773-1776 ◽  
Author(s):  
Zheman Xiao ◽  
Zuneng Lu ◽  
Zhongchun Liu ◽  
Wanhong Liu ◽  
Lijun Li ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Superior Cervical Ganglion ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Cervical Ganglion ◽  
Ganglion Neurons

scholarly journals Chlorogenic acid alters the voltage-gated potassium channel currents of trigeminal ganglion neurons

2014 ◽  
Vol 6 (4) ◽  
pp. 233-240 ◽  
Author(s):  
Yu-Jiao Zhang ◽  
Xiao-Wen Lu ◽  
Ning Song ◽  
Liang Kou ◽  
Min-Ke Wu ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Chlorogenic Acid ◽  
Trigeminal Ganglion ◽  
Voltage Gated ◽  
Trigeminal Ganglion Neurons ◽  
Ganglion Neurons ◽  
Channel Currents

scholarly journals Conserved Expression of Nav1.7 and Nav1.8 Contribute to the Spontaneous and Thermally Evoked Excitability in IL-6 and NGF-Sensitized Adult Dorsal Root Ganglion Neurons In Vitro

2020 ◽  
Vol 7 (2) ◽  
pp. 44
Author(s):  
Rahul R. Atmaramani ◽  
Bryan J. Black ◽  
June Bryan de la Peña ◽  
Zachary T. Campbell ◽  
Joseph J. Pancrazio
Keyword(s):  
Sodium Channels ◽  
Sensory Neurons ◽  
Inflammatory Pain ◽  
Dorsal Root Ganglion Neurons ◽  
Electrode Arrays ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Ganglion Neurons

Sensory neurons respond to noxious stimuli by relaying information from the periphery to the central nervous system via action potentials driven by voltage-gated sodium channels, specifically Nav1.7 and Nav1.8. These channels play a key role in the manifestation of inflammatory pain. The ability to screen compounds that modulate voltage-gated sodium channels using cell-based assays assumes that key channels present in vivo is maintained in vitro. Prior electrophysiological work in vitro utilized acutely dissociated tissues, however, maintaining this preparation for long periods is difficult. A potential alternative involves multi-electrode arrays which permit long-term measurements of neural spike activity and are well suited for assessing persistent sensitization consistent with chronic pain. Here, we demonstrate that the addition of two inflammatory mediators associated with chronic inflammatory pain, nerve growth factor (NGF) and interleukin-6 (IL-6), to adult DRG neurons increases their firing rates on multi-electrode arrays in vitro. Nav1.7 and Nav1.8 proteins are readily detected in cultured neurons and contribute to evoked activity. The blockade of both Nav1.7 and Nav1.8, has a profound impact on thermally evoked firing after treatment with IL-6 and NGF. This work underscores the utility of multi-electrode arrays for pharmacological studies of sensory neurons and may facilitate the discovery and mechanistic analyses of anti-nociceptive compounds.

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