Effect of amitriptyline on tetrodotoxin-resistant Nav1.9 currents in nociceptive trigeminal neurons

Molecular Pain

Shengyuan Yu²  Jianquan Zheng¹  Xiaoyan Liu¹  Jingyao Liang² 

[1] Department of Biochemical Pharmacology, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, PR China;Department of Neurology, Chinese PLA General Hospital, Beijing 100853, PR China

关键词: Pain;    Trigeminal ganglion;    Patch clamp;    Na_v1.9;    Amitriptyline;   

Others  :  862433
DOI  :  10.1186/1744-8069-9-31

 received in 2013-01-26, accepted in 2013-06-14,  发布年份 2013

【 摘 要 】

Background

Amitriptyline (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 Na_v1.9 currents have been unclear to present.

Results

Using a whole-cell patch clamp technique, this study showed that AMI efficiently inhibited Na_v1.9 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 Na_v1.9 channels in the hyperpolarizing direction without affecting voltage-dependent activation. Surprisingly, neither 10 nor 50 μM AMI caused a use-dependent blockade of Na_v1.9 currents elicited by 60 pulses at 1 Hz.

Conclusion

These data suggest that AMI is a state-selective blocker of Na_v1.9 channels in rat nociceptive trigeminal neurons, which likely contributes to the efficacy of AMI in treating various pains, including migraines.

【 授权许可】

   
2013 Liang et al.; licensee BioMed Central Ltd.

【 图 表 】

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