title: Functional up-regulation of Nav1.8 sodium channel on dorsal root ganglia neurons contributes to the induction of scorpion sting pain.
abstract: 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.
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Ye
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Hua
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China.
authors.forename: Yunlu
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China.
authors.forename: Shichao
authors.initials: S
authors.lastname: Qin
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Fu
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou 215021, China yhji@staff.shu.edu.cn liutong80@suda.edu.cn.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Laboratory of Neuropharmacology and Neurotoxicology, Shanghai University, Shanghai 200436, China yhji@staff.shu.edu.cn liutong80@suda.edu.cn.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000814:Aniline Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D005620:Freund's Adjuvant / Q000633:toxicity; D005663:Furans / Q000008:administration & dosage / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology*; D055785:Gene Knockdown Techniques; D007278:Injections, Spinal; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008959:Models, Neurological; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D065008:Scorpion Stings / Q000235:genetics / Q000503:physiopathology*; D012604:Scorpion Venoms / Q000633:toxicity; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C520740:A 803467; D000814:Aniline Compounds; D005663:Furans; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568319:Scn10a protein, rat; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; C105338:makatoxin I; D005620:Freund's Adjuvant
keywords: BmK I; Nav1.8; pain; voltage-gated sodium channel