Jingyao Liang, Xiaoyan Liu, Jianquan Zheng
Jan 1, 2013
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0
Influential Citations
29
Citations
Quality indicators
Journal
Molecular Pain
Abstract
BackgroundAmitriptyline (AMI) is tricyclic antidepressant that has been widely used to manage various chronic pains such as migraines. Its efficacy is attributed to its blockade of voltage-gated sodium channels (VGSCs). However, the effects of AMI on the tetrodotoxin-resistant (TTX-r) sodium channel Nav1.9 currents have been unclear to present.ResultsUsing a whole-cell patch clamp technique, this study showed that AMI efficiently inhibited Nav1.9 currents in a concentration-dependent manner and had an IC50 of 15.16 μM in acute isolated trigeminal ganglion (TG) neurons of the rats. 10 μM AMI significantly shifted the steady-state inactivation of Nav1.9 channels in the hyperpolarizing direction without affecting voltage-dependent activation. Surprisingly, neither 10 nor 50 μM AMI caused a use-dependent blockade of Nav1.9 currents elicited by 60 pulses at 1 Hz.ConclusionThese data suggest that AMI is a state-selective blocker of Nav1.9 channels in rat nociceptive trigeminal neurons, which likely contributes to the efficacy of AMI in treating various pains, including migraines.