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Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders

Joost P.H. Drenth, Stephen G. Waxman

Joost P.H. Drenth, Stephen G. Waxman

Published December 3, 2007
Citation Information: J Clin Invest. 2007;117(12):3603-3609. https://doi.org/10.1172/JCI33297.

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Na(v)1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Fu W, Vasylyev D, Bi Y, Zhang M, Sun G, Khleborodova A, Huang G, Zhao L, Zhou R, Li Y, Liu S, Cai X, He W, Cui M, Zhao X, Hettinghouse A, Good J, Kim E, Strauss E, Leucht P, Schwarzkopf R, Guo EX, Samuels J, Hu W, Attur M, Waxman SG, Liu CJ	Nature	2024
Erythromelalgia caused by the missense mutation p.Arg220Pro in an alternatively spliced exon of SCN9A (NaV1.7). Deuis JR, Kumble S, Keramidas A, Ragnarsson L, Simons C, Pais L, White SM, Vetter I	Human Molecular Genetics	2024
Heterologous expression of the human wild-type and variant NaV1.8 (A1073V) in rat sensory neurons Kapur MM, Soliman M, Blanke EN, Herold PB, Janicki PK, Vrana KE, Coates MD, Ruiz-Velasco V	Neurogastroenterology and Motility	2024
Mature neurons from iPSCs unveil neurodegeneration-related pathways in mucopolysaccharidosis type II: GSK-3β inhibition for therapeutic potential Chen TY, Lin SP, Huang DF, Huang HS, Tsai FC, Lee LJ, Lin HY, Huang HP	Cell Death and Disease	2024
Ion channels in osteoarthritis: emerging roles and potential targets. Zhou R, Fu W, Vasylyev D, Waxman SG, Liu CJ	Nature reviews. Rheumatology	2024
Mapping structural distribution and gating-property impacts of disease-associated mutations in voltage-gated sodium channels. Akbari Ahangar A, Elhanafy E, Blanton H, Li J	iScience	2024
A Novel Antigen Design Strategy to Isolate Single-Domain Antibodies that Target Human Nav1.7 and Reduce Pain in Animal Models. Martina M, Banderali U, Yogi A, Arbabi Ghahroudi M, Liu H, Sulea T, Durocher Y, Hussack G, van Faassen H, Chakravarty B, Liu QY, Iqbal U, Ling B, Lessard E, Sheff J, Robotham A, Callaghan D, Moreno M, Comas T, Ly D, Stanimirovic D	Advanced science (Weinheim, Baden-Wurttemberg, Germany)	2024
Paroxysmal extreme pain disorder associated with a mutation in SCN9A gene – Case report and own experiences Szczupak M, Wierzchowska J, Cimoszko-Zauliczna M, Kobak J, Kosydar-Bochenek J, Radys W, Szlagatys-Sidorkiewicz A, Religa D, Krupa-Nurcek S	Frontiers in Neurology	2024
Striving toward hyperthermia-free analgesia: Lessons from loss-of-function mutations of human TRPV1 Man-Kyo Chung	Journal of Clinical Investigation	2023
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Distinguishing Loss-of-Function and Gain-of-Function SCN8A Variants Using a Random Forest Classification Model Trained on Clinical Features Hack JB, Horning K, Juroske Short DM, Schreiber JM, Watkins JC, Hammer MF		2023
A Review of the Therapeutic Targeting of SCN9A and Nav1.7 for Pain Relief in Current Human Clinical Trials Dormer A, Narayanan M, Schentag J, Achinko D, Norman E, Kerrigan J, Jay G, Heydorn W	Journal of pain research	2023
Nav 1.7 gain-of-function mutation I228M triggers age-dependent nociceptive insensitivity and C-LTMR dysregulation Wimalasena NK, Taub DG, Shim J, Hakim S, Kawaguchi R, Chen L, El-Rifai M, Geschwind DH, Dib-Hajj SD, Waxman SG, Woolf CJ	Experimental Neurology	2023
Elucidating Molecular Mechanisms of Protoxin-2 State-specific Binding to the Human NaV1.7 Channel Ngo K, Mateos DL, Han Y, Rouen KC, Ahn SH, Wulff H, Clancy CE, Yarov-Yarovoy V, Vorobyov I		2023
Clinical Characterization of Pediatric Erythromelalgia: A Single-Center Case Series Sun J, Ocay DD, Halpin M, Lobo K, Frohman DF, Donado C, Brownstein CA, Genetti CA, Madden A, Berde CB	Children	2023
TRPA1 rare variants in chronic neuropathic and nociplastic pain patients Marchi M, Salvi E, Andelic M, Mehmeti E, D'Amato I, Cazzato D, Chiappori F, Lombardi R, Cartelli D, Devigili G, Dalla Bella E, Gerrits M, Almomani R, Malik RA, Ślęczkowska M, Mazzeo A, Gentile L, Dib-Hajj S, Waxman SG, Faber CG, Vecchio E, de Tommaso M, Lauria G	PAIN	2023
Mapping Structural Distribution and Gating-Property Impacts of Disease-Associated Missense Mutations in Voltage-Gated Sodium Channels Ahangar AA, Elhanafy E, Blanton H, Li J		2023
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Population Study of Hand and Wrist Manifestations of Congenital Insensitivity to Pain Spiteri M, Mifsud M, Azzopardi T, Giele H	Hand (New York, N.Y.)	2020
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Sporadic Erythromelalgia Associated with a Homozygous Carrier of Common Missense Polymorphism in SCN9A Gene Coding for NaV1.7 Voltage-gated Sodium Channel PK Janicki, V Ruiz-Velasco, S Adhikary	Cureus	2019
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Determination of the μ-Conotoxin PIIIA Specificity Against Voltage-Gated Sodium Channels from Binding Energy Calculations F Chen, W Huang, T Jiang, R Yu	Marine drugs	2018
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Effects of Lidocaine and Articaine on Neuronal Survival and Recovery F Albalawi, JC Lim, KV DiRenzo, EV Hersh, CH Mitchell	Anesthesia Progress	2018
Brain activity associated with pain in inherited erythromelalgia: stimulus-free pain engages brain areas involved in valuation and learning P Geha, BR Schulman, SD Dib-Hajj, SG Waxman	Neurobiology of Pain	2018
Bulleyaconitine A attenuates hyperexcitability of dorsal root ganglion neurons induced by spared nerve injury: The role of preferably blocking Nav1.7 and Nav1.3 channels MX Xie, J Yang, RP Pang, WA Zeng, HD Ouyang, YQ Liu, XG Liu	Molecular Pain	2018
Resilience to Pain: A Peripheral Component Identified Using Induced Pluripotent Stem Cells and Dynamic Clamp MA Mis, Y Yang, BS Tanaka, C Gomis-Perez, S Liu, F Dib-Hajj, T Adi, R Garcia-Milian, BR Schulman, SD Dib-Hajj, SG Waxman	The Journal of neuroscience : the official journal of the Society for Neuroscience	2018
Introducing Critical Pain Related Genes: A System Biology Approach MR Tavirani, SR Tavirani, MM Zadeh-Esmaeel, NA Ahmadi	Basic and Clinical Neuroscience Journal	2018
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Reverse pharmacogenomics: carbamazepine normalizes activation and attenuates thermal hyperexcitability of sensory neurons due to Na v 1.7 mutation I234T: Carbamazepine-responsive Na v 1.7-I234T Y Yang, T Adi, PR Effraim, L Chen, SD Dib-Hajj, SG Waxman	British Journal of Pharmacology	2017
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Transcriptomic analyses of genes and tissues in inherited sensory neuropathies MR Sapio, SC Goswami, JR Gross, AJ Mannes, MJ Iadarola	Experimental Neurology	2016
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The Domain II S4-S5 Linker in Nav1.9: A Missense Mutation Enhances Activation, Impairs Fast Inactivation, and Produces Human Painful Neuropathy C Han, Y Yang, BT de Greef, JG Hoeijmakers, MM Gerrits, C Verhamme, J Qu, G Lauria, IS Merkies, CG Faber, SD Dib-Hajj, SG Waxman	NeuroMolecular Medicine	2015
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Painful micturition in a small child: an unusual clinical picture of paroxysmal extreme pain disorder A Meglič, M Perkovič-Benedik, KT Podkrajšek, S Bertok	Pediatric Nephrology	2014
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The Role of Sodium Channels in Painful Diabetic and Idiopathic Neuropathy G Lauria, D Ziegler, R Malik, IS Merkies, SG Waxman, CG Faber	Current Diabetes Reports	2014
Synthesis and Analgesic Effects of μ-TRTX-Hhn1b on Models of Inflammatory and Neuropathic Pain Y Liu, J Tang, Y Zhang, X Xun, D Tang, D Peng, J Yi, Z Liu, X Shi	Toxins	2014
Depolarized Inactivation Overcomes Impaired Activation to Produce DRG Neuron Hyperexcitability in a Nav1.7 Mutation in a Patient with Distal Limb Pain J Huang, Y Yang, SD Dib-Hajj, M van Es, P Zhao, J Salomon, JP Drenth, SG Waxman	The Journal of neuroscience : the official journal of the Society for Neuroscience	2014
Validating therapeutic targets through human genetics RM Plenge, EM Scolnick, D Altshuler	Nature Reviews Drug Discovery	2013
Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels K McCormack, S Santos, ML Chapman, DS Krafte, BE Marron, CW West, MJ Krambis, BM Antonio, SG Zellmer, D Printzenhoff, KM Padilla, Z Lin, PK Wagoner, NA Swain, PA Stupple, M Groot, RP Butt, NA Castle	Proceedings of the National Academy of Sciences	2013
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Pain Prevalence and Trajectories Following Pediatric Spinal Fusion Surgery CB Sieberg, LE Simons, MR Edelstein, MR DeAngelis, M Pielech, N Sethna, MT Hresko	The Journal of Pain	2013
Linkage between increased nociception and olfaction via a SCN9A haplotype D Heimann, J Lötsch, T Hummel, A Doehring, BG Oertel	PloS one	2013
A novel SCN9A mutation responsible for primary erythromelalgia and is resistant to the treatment of sodium channel blockers MT Wu, PY Huang, CT Yen, CC Chen, MJ Lee	PloS one	2013
Evaluation of behavior and expression of NaV1.7 in dorsal root ganglia after sciatic nerve compression and application of nucleus pulposus in rats M Mukai, Y Sakuma, M Suzuki, S Orita, K Yamauchi, G Inoue, Y Aoki, T Ishikawa, M Miyagi, H Kamoda, G Kubota, Y Oikawa, K Inage, T Sainoh, J Sato, J Nakamura, M Takaso, T Toyone, K Takahashi, S Ohtori	European Spine Journal	2013
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Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy M Chattopadhyay, Z Zhou, S Hao, M Mata, DJ Fink	Molecular Pain	2012
Small-fibre neuropathies—advances in diagnosis, pathophysiology and management JG Hoeijmakers, CG Faber, G Lauria, IS Merkies, SG Waxman	Nature Reviews Neurology	2012
The NaV1.7 sodium channel: from molecule to man SD Dib-Hajj, Y Yang, JA Black, SG Waxman	Nature Reviews Neuroscience	2012
The non-synonymous SNP, R1150W, in SCN9A is not associated with chronic widespread pain susceptibility KL Holliday, W Thomson, T Neogi, DT Felson, K Wang, FC Wu, IT Huhtaniemi, G Bartfai, F Casanueva, G Forti, K Kula, M Punab, D Vanderschueren, GJ Macfarlane, MA Horan, W Ollier, A Payton, N Pendleton, J McBeth	Molecular Pain	2012
Structural homology modeling and mutant cycle analysis predict pharmacoresponsiveness of a NaV1.7 mutant channel Y Yang, SD Dib-Hajj, J Zhang, Y Zhang, L Tyrrell, M Estacion, SG Waxman	Nature Communications	2012
Sodium Channel Nav1.7 Is Essential for Lowering Heat Pain Threshold after Burn Injury SD Shields, X Cheng, N Uceyler, C Sommer, SD Dib-Hajj, SG Waxman	The Journal of neuroscience : the official journal of the Society for Neuroscience	2012
Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons RG Xie, DW Zheng, JL Xing, XJ Zhang, Y Song, YB Xie, F Kuang, H Dong, SW You, H Xu, SJ Hu	PloS one	2011
Recent Advances in the Understanding of Genetic Susceptibility to Chronic Pain and Somatic Symptoms KL Holliday, J McBeth	Current Rheumatology Reports	2011
Intra- and interfamily phenotypic diversity in pain syndromes associated with a gain-of-function variant of NaV1.7 M Estacion, C Han, JS Choi, JG Hoeijmakers, G Lauria, JP Drenth, MM Gerrits, SD Dib-Hajj, CG Faber, IS Merkies, SG Waxman	Molecular Pain	2011
Vector-mediated release of GABA attenuates pain-related behaviors and reduces NaV1.7 in DRG neurons M Chattopadhyay, M Mata, DJ Fink	European journal of pain (London, England)	2011
Common Molecular Determinants of Tarantula Huwentoxin-IV Inhibition of Na+ Channel Voltage Sensors in Domains II and IV* Y Xiao, JO 2nd, S Liang, TR Cummins	The Journal of biological chemistry	2011
Genetic basis of pain variability: recent advances EE Young, WR Lariviere, I Belfer	Journal of medical genetics	2011
Heat Avoidance Is Regulated by Transient Receptor Potential (TRP) Channels and a Neuropeptide Signaling Pathway in Caenorhabditis elegans DA Glauser, WC Chen, R Agin, BL MacInnis, AB Hellman, PA Garrity, MW Tan, MB Goodman	Genetics	2011
Getting pharmaceutical R&D back on target ME Bunnage	Nature Chemical Biology	2011
Pain as a channelopathy Ramin Raouf, Kathryn Quick, John N. Wood	Journal of Clinical Investigation	2010
The discovery and development of analgesics: new mechanisms new modalities Gillian Burgess, Dic Williams	Journal of Clinical Investigation	2010
Mutations at opposite ends of the DIII/S4-S5 linker of sodium channel Na V 1.7 produce distinct pain disorders X Cheng, SD Dib-Hajj, L Tyrrell, DA Wright, TZ Fischer, SG Waxman	Molecular Pain	2010
How to improve R&D productivity: the pharmaceutical industry's grand challenge SM Paul, DS Mytelka, CT Dunwiddie, CC Persinger, BH Munos, SR Lindborg, AL Schacht	Nature Reviews Drug Discovery	2010
Paroxysmal extreme pain disorder: a molecular lesion of peripheral neurons JS Choi, F Boralevi, O Brissaud, J Sánchez-Martín, RH Morsche, SD Dib-Hajj, JP Drenth, SG Waxman	Nature Reviews Neurology	2010
Pain perception is altered by a nucleotide polymorphism in SCN9A F Reimann, JJ Cox, I Belfer, L Diatchenko, DV Zaykin, DP McHale, JP Drenth, F Dai, J Wheeler, F Sanders, L Wood, TX Wu, J Karppinen, L Nikolajsen, M Männikkö, MB Max, C Kiselycznyk, M Poddar, RH Morsche, S Smith, D Gibson, A Kelempisioti, W Maixner, FM Gribble, CG Woods	Proceedings of the National Academy of Sciences	2010
Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations JJ Cox, J Sheynin, Z Shorer, F Reimann, AK Nicholas, L Zubovic, M Baralle, E Wraige, E Manor, J Levy, CG Woods, R Parvari	Human Mutation	2010
A nonsense mutation in the SCN9A gene in congenital insensitivity to pain M Kurban, M Wajid, Y Shimomura, AM Christiano	Dermatology (Basel, Switzerland)	2010
Sodium channel Na v 1.7 immunoreactivity in painful human dental pulp and burning mouth syndrome K Beneng, T Renton, Z Yilmaz, Y Yiangou, P Anand	BMC neuroscience	2010
Expression genetics identifies spinal mechanisms supporting formalin late phase behaviors X Li, P Sahbaie, M Zheng, J Ritchie, G Peltz, JS Mogil, JD Clark	Molecular Pain	2010
Two Novel Mutations of SCN9A (Nav1.7) are Associated with Partial Congenital Insensitivity to Pain R Staud, DD Price, D Janicke, E Andrade, AG Hadjipanayis, WT Eaton, L Kaplan, MR Wallace	European journal of pain (London, England)	2010
A Gain-of-Function Mutation in TRPA1 Causes Familial Episodic Pain Syndrome B Kremeyer, F Lopera, JJ Cox, A Momin, F Rugiero, S Marsh, CG Woods, NG Jones, KJ Paterson, FR Fricker, A Villegas, N Acosta, NG Pineda-Trujillo, JD Ramírez, J Zea, MW Burley, G Bedoya, DL Bennett, JN Wood, A Ruiz-Linares	Neuron	2010
Sodium channelopathies and pain A Lampert, AO OReilly, P Reeh, A Leffler	Pflügers Archiv - European Journal of Physiology	2010
Pulmonary surfactant: an immunological perspective ZC Chroneos, Z Sever-Chroneos, VL Shepherd	Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology	2009
Visualizing sodium dynamics in isolated cardiomyocytes using fluorescent nanosensors JM Dubach, S Das, A Rosenzweig, HA Clark	Proceedings of the National Academy of Sciences	2009
Developments in autonomic research: a review of the latest literature VG Macefield	Clinical Autonomic Research	2009
Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage M Costigan, J Scholz, CJ Woolf	Annual Review of Neuroscience	2009
Sodium channel blockers for the treatment of neuropathic pain A Bhattacharya, AD Wickenden, SR Chaplan	Neurotherapeutics	2009
Ranolazine attenuates behavioral signs of neuropathic pain HJ 3rd, C Garrett, RR Donahue, D Paul, I Diamond, BK Taylor	Behavioural Pharmacology	2009
A novel Nav1.7 mutation producing carbamazepine-responsive erythromelalgia TZ Fischer, ES Gilmore, M Estacion, E Eastman, S Taylor, M Melanson, SD Dib-Hajj, SG Waxman	Annals of Neurology	2009
A case of primary erythermalgia with encephalopathy J Seneschal, G Solé, A Taieb, X Ferrer	Journal of Neurology	2009
Late-onset erythromelalgia in a previously healthy young woman: a case report and review of the literature S Gaur, T Koroscil	Journal of medical case reports	2009
Compound heterozygosity in sodium channel Nav1.7 in a family with hereditary erythermalgia ME Samuels, RH Morsche, ME Lynch, JP Drenth	Molecular Pain	2008
Inherited Neuronal Ion Channelopathies: New Windows on Complex Neurological Diseases WA Catterall, S Dib-Hajj, MH Meisler, D Pietrobon	The Journal of neuroscience : the official journal of the Society for Neuroscience	2008
NaV1.7 Gain-of-Function Mutations as a Continuum: A1632E Displays Physiological Changes Associated with Erythromelalgia and Paroxysmal Extreme Pain Disorder Mutations and Produces Symptoms of Both Disorders M Estacion, SD Dib-Hajj, PJ Benke, RH Morsche, EM Eastman, LJ Macala, JP Drenth, SG Waxman	The Journal of neuroscience : the official journal of the Society for Neuroscience	2008
Sodium Channel β1 Regulatory Subunit Deficiency Reduces Pancreatic Islet Glucose-Stimulated Insulin and Glucagon Secretion SJ Ernst, L Aguilar-Bryan, JL Noebels	Endocrinology	2008

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