Abstract

Liming Hua^1,†,

Yunlu Jiao¹,

Zhenwei Li¹,

Shichao Qin¹,

Jin Fu¹,

Feng Jiang¹,

Tong Liu^2,* and

Yonghua Ji^1,*

²Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou 215021, China

^† These authors contributed equally to this work.

Abstract  Received July 2, 2015.

Accepted August 2, 2015.

BmK I, purified from the venom of scorpion Buthus martensi Karsch (BmK), is a receptor site-3-specific modulator of voltage-gated sodium channels (VGSCs) and can induce pain-related behaviors in rats. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 contributes to most of the sodium current underlying the action potential upstroke in dorsal root ganglia (DRG) neurons and may serve as a critical ion channel targeted by BmK I. Herein, using electrophysiological, molecular, and behavioral approaches, we investigated whether the aberrant expression of Nav1.8 in DRG contributes to generation of pain induced by BmK I. The expression of Nav1.8 was found to be significantly increased at both mRNA and protein levels following intraplantar injection of BmK I in rats. In addition, the current density of TTX-R Nav1.8 sodium channel is significantly increased and the gating kinetics of Nav1.8 is also altered in DRG neurons from BmK I-treated rats. Furthermore, spontaneous pain and mechanical allodynia, but not thermal hyperalgesia induced by BmK I, are significantly alleviated through either blockade of the Nav1.8 sodium channel by its selective blocker A-803467 or knockdown of the Nav1.8 expression in DRG by antisense oligodeoxynucleotide (AS-ODN) targeting Nav1.8 in rats. Finally, BmK I was shown to induce enhanced pain behaviors in complete freund’s adjuvant (CFA)-inflamed rats, which was partly due to the over-expression of Nav1.8 in DRG. Our results suggest that functional up-regulation of Nav1.8 channel on DRG neurons contributes to the development of BmK I-induced pain in rats.

Keywords   pain; voltage-gated sodium channel; Nav1.8; BmK I

Received   2015-7-2　　

Accepted  2015-8-2

Funding  This work was supported by the grants from the National Basic Research Program of China (No. 2010CB529806), the National Natural Science Foundation of China (Nos. 31171064, 81402903, 31371179 and 81300968), the Key Research Program of Science and Technolo

* Correspondence address  Tel: +86-21-66135189; E-mail: [email protected] (Y.J.) / Tel: +86-512-65883193; E-mail: [email protected] (T.L.)