title: Functional upregulation of nav1.8 sodium channels on the membrane of dorsal root Ganglia neurons contributes to the development of cancer-induced bone pain.
abstract: We have previously reported that enhanced excitability of dorsal root ganglia (DRG) neurons contributes to the development of bone cancer pain, which severely decreases the quality of life of cancer patients. Nav1.8, a tetrodotoxin-resistant (TTX-R) sodium channel, contributes most of the sodium current underlying the action potential upstroke and accounts for most of the current in later spikes in a train. We speculate that the Nav1.8 sodium channel is a potential candidate responsible for the enhanced excitability of DRG neurons in rats with bone cancer pain. Here, using electrophysiology, Western blot and behavior assays, we documented that the current density of TTX-R sodium channels, especially the Nav1.8 channel, increased significantly in DRG neurons of rats with cancer-induced bone pain. This increase may be due to an increased expression of Nav1.8 on the membrane of DRG neurons. Accordantly, blockade of Nav1.8 sodium channels by its selective blocker A-803467 significantly alleviated the cancer-induced mechanical allodynia and thermal hyperalgesia in rats. Taken together, these results suggest that functional upregulation of Nav1.8 channels on the membrane of DRG neurons contributes to the development of cancer-induced bone pain.
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, People's Republic of China; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Liu
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, People's Republic of China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Fang
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, People's Republic of China; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: You
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Neuroscience Research Institute, Peking University, Beijing, People's Republic of China; Department of Neurobiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People's Republic of China; Key Laboratory for Neuroscience, Ministry of Education and Ministry of Health, Beijing, People's Republic of China.
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Xing
mesh_terms: D000814:Aniline Compounds / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001859:Bone Neoplasms / Q000150:complications*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D055724:Electrophysiological Phenomena / Q000187:drug effects; D005260:Female; D005663:Furans / Q000494:pharmacology / Q000627:therapeutic use; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; 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; D026941:Sodium Channel Blockers