Acta biochimica et biophysica Sinica
-
Acta Biochim. Biophys. Sin. (Shanghai) · Feb 2016
Functional up-regulation of Nav1.8 sodium channel on dorsal root ganglia neurons contributes to the induction of scorpion sting pain.
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. ⋯ 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.