Gene Symbol: Scn10a
Description: sodium voltage-gated channel alpha subunit 10
Alias: Na(V)1.8, Nav1.8, PN3, sodium channel protein type 10 subunit alpha, peripheral nerve sodium channel 3, sensory neuron sodium channel, sodium channel protein type X subunit alpha, sodium channel type X alpha polypeptide, sodium channel voltage-gated type X alpha polypeptide, sodium channel, voltage-gated, type 10, alpha polypeptide, sodium channel, voltage-gated, type X, alpha subunit, voltage-gated sodium channel subunit alpha Nav1.8
Species: rat
Products:     Scn10a

Top Publications

  1. Rush A, Craner M, Kageyama T, Dib Hajj S, Waxman S, Ranscht B. Contactin regulates the current density and axonal expression of tetrodotoxin-resistant but not tetrodotoxin-sensitive sodium channels in DRG neurons. Eur J Neurosci. 2005;22:39-49 pubmed
  2. Schuelert N, McDougall J. Involvement of Nav 1.8 sodium ion channels in the transduction of mechanical pain in a rodent model of osteoarthritis. Arthritis Res Ther. 2012;14:R5 pubmed publisher
    ..Targeting the Nav1.8 sodium channel on joint nociceptors could therefore be useful for the treatment of OA pain, avoiding the unwanted side effects of non-selective nerve blocks. ..
  3. Zimmermann K, Leffler A, Babes A, Cendan C, Carr R, Kobayashi J, et al. Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures. Nature. 2007;447:855-8 pubmed
    ..Our data present strong evidence for a specialized role of Na(v)1.8 in nociceptors as the critical molecule for the perception of cold pain and pain in the cold. ..
  4. Rabert D, Koch B, Ilnicka M, Obernolte R, Naylor S, Herman R, et al. A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A. Pain. 1998;78:107-14 pubmed
    ..In this study, a human sodium channel (hPN3, SCN10A) has been cloned from the lumbar 4/5 dorsal root ganglia (DRG)...
  5. Okuse K, Malik Hall M, Baker M, Poon W, Kong H, Chao M, et al. Annexin II light chain regulates sensory neuron-specific sodium channel expression. Nature. 2002;417:653-6 pubmed
    ..Because direct association with p11 is required for functional expression of Na(V)1.8, disrupting this interaction may be a useful new approach to downregulating Na(V)1.8 and effecting analgesia. ..
  6. Joshi S, Honore P, Hernandez G, Schmidt R, Gomtsyan A, Scanio M, et al. Additive antinociceptive effects of the selective Nav1.8 blocker A-803467 and selective TRPV1 antagonists in rat inflammatory and neuropathic pain models. J Pain. 2009;10:306-15 pubmed publisher
    ..The 2 classes of novel antinociceptive agents produced an additive interaction in attenuating CFA-induced thermal hyperalgesia, providing a rationale for their use as a combination strategy in the clinic for treating inflammatory pain. ..
  7. Poon W, Malik Hall M, Wood J, Okuse K. Identification of binding domains in the sodium channel Na(V)1.8 intracellular N-terminal region and annexin II light chain p11. FEBS Lett. 2004;558:114-8 pubmed
    ..As Na(V)1.8 channel expression is associated with pain pathways, drugs that disrupt the Na(V)1.8-p11 interaction and down-regulate channel expression may have analgesic activity. ..
  8. Yu Y, Zhao F, Guan S, Chen J. Antisense-mediated knockdown of Na(V)1.8, but not Na(V)1.9, generates inhibitory effects on complete Freund's adjuvant-induced inflammatory pain in rat. PLoS ONE. 2011;6:e19865 pubmed publisher
  9. Joshi S, Mikusa J, Hernandez G, Baker S, Shieh C, Neelands T, et al. Involvement of the TTX-resistant sodium channel Nav 1.8 in inflammatory and neuropathic, but not post-operative, pain states. Pain. 2006;123:75-82 pubmed
    ..6+/-6.2% effect, p<0.05 vs. MM). These data demonstrate a greater involvement of Nav 1.8 in frank nerve injury and inflammatory pain as compared to acute, post-operative or chemotherapy-induced neuropathic pain states. ..

More Information


  1. Strickland I, Martindale J, Woodhams P, Reeve A, Chessell I, McQueen D. Changes in the expression of NaV1.7, NaV1.8 and NaV1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain. Eur J Pain. 2008;12:564-72 pubmed
    ..The increased presence of these channels suggests that Na(V)1.7, Na(V)1.8 and Na(V)1.9 play a role, at least in part, in the maintenance of chronic inflammatory pain several weeks after the initial insult. ..
  2. Moon J, Song S, Yoon S, Roh D, Kang S, Park J, et al. The differential effect of intrathecal Nav1.8 blockers on the induction and maintenance of capsaicin- and peripheral ischemia-induced mechanical allodynia and thermal hyperalgesia. Anesth Analg. 2012;114:215-23 pubmed publisher
    ..8 blockers. These findings suggest that early treatment with a Nav1.8 blocker can be an important factor in the clinical management of chronic MA associated with inflammatory and ischemic pain. ..
  3. Miao X, Gao X, Wu J, Lu Z, Huang Z, Li X, et al. Bilateral downregulation of Nav1.8 in dorsal root ganglia of rats with bone cancer pain induced by inoculation with Walker 256 breast tumor cells. BMC Cancer. 2010;10:216 pubmed publisher
    ..The voltage-gated sodium channel Nav1.8 plays a critical role in many aspects of nociceptor function. Therefore, we characterized a rat model of cancer pain and investigated the potential role of Nav1.8...
  4. Gold M, Weinreich D, Kim C, Wang R, Treanor J, Porreca F, et al. Redistribution of Na(V)1.8 in uninjured axons enables neuropathic pain. J Neurosci. 2003;23:158-66 pubmed
    ..These observations suggest that aberrant activity in uninjured C-fibers is a necessary component of pain associated with partial nerve injury. They also suggest that blocking Na(V)1.8 would be an effective treatment of neuropathic pain. ..
  5. Benn S, Costigan M, Tate S, Fitzgerald M, Woolf C. Developmental expression of the TTX-resistant voltage-gated sodium channels Nav1.8 (SNS) and Nav1.9 (SNS2) in primary sensory neurons. J Neurosci. 2001;21:6077-85 pubmed
    ..SNS/PN3) and Na(v)1.9 (SNS2/NaN), in developing rat lumbar dorsal root ganglia (DRGs). Expression of both Na(v)1...
  6. Akopian A, Sivilotti L, Wood J. A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature. 1996;379:257-62 pubmed
    ..As some noxious input into the spinal cord is resistant to tetrodotoxin, block of expression or function of such a C-fibre-restricted sodium channel may have a selective analgesic effect. ..
  7. Thakor D, Lin A, Matsuka Y, Meyer E, Ruangsri S, Nishimura I, et al. Increased peripheral nerve excitability and local NaV1.8 mRNA up-regulation in painful neuropathy. Mol Pain. 2009;5:14 pubmed publisher
    ..8 immunoreactivity in rat sciatic nerves. The concomitant axonal accumulation of NaV1.8 mRNA may play a role in the pathogenesis of this model of neuropathic pain. ..
  8. Liu C, Li Q, Su Y, Bao L. Prostaglandin E2 promotes Na1.8 trafficking via its intracellular RRR motif through the protein kinase A pathway. Traffic. 2010;11:405-17 pubmed publisher
    ..8 current in DRG neurons. Our data indicate that PGE(2) promotes the surface expression of Na(v)1.8 via an intracellular RRR motif, and provide a novel mechanism for functional modulation of Na(v)1.8 by hyperalgesic agents. ..
  9. Ruangsri S, Lin A, Mulpuri Y, Lee K, Spigelman I, Nishimura I. Relationship of axonal voltage-gated sodium channel 1.8 (NaV1.8) mRNA accumulation to sciatic nerve injury-induced painful neuropathy in rats. J Biol Chem. 2011;286:39836-47 pubmed publisher
    ..8 RNA were unaffected by SNE or shRNA treatments, suggesting that transcription of the Scn10a gene encoding NaV1.8 was unchanged...
  10. Malik Hall M, Poon W, Baker M, Wood J, Okuse K. Sensory neuron proteins interact with the intracellular domains of sodium channel NaV1.8. Brain Res Mol Brain Res. 2003;110:298-304 pubmed
    ..Immunoprecipitation (pull-down) assays confirm that some of the proteins interact with, and may hence regulate, Na(V)1.8 in vivo. ..
  11. Qiu F, Jiang Y, Zhang H, Liu Y, Mi W. Increased expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 within dorsal root ganglia in a rat model of bone cancer pain. Neurosci Lett. 2012;512:61-6 pubmed publisher
    ..8 (SNS/PN3) and Nav1.9 (SNS2/NaN), in dorsal root ganglia (DRG) neurons in an animal model of bone cancer pain...
  12. Xu W, Zhang J, Wang Y, Wang L, Wang X. Changes in the expression of voltage-gated sodium channels Nav1.3, Nav1.7, Nav1.8, and Nav1.9 in rat trigeminal ganglia following chronic constriction injury. Neuroreport. 2016;27:929-34 pubmed publisher
    ..3 and downregulation of Nav1.7, Nav1.8, and Nav1.9 messenger RNA and protein levels. Our findings suggest that VGSC may participate in the regulation of TN. ..
  13. Liu X, Yang J, Fang D, Cai J, Wan Y, Xing G. Functional upregulation of nav1.8 sodium channels on the membrane of dorsal root Ganglia neurons contributes to the development of cancer-induced bone pain. PLoS ONE. 2014;9:e114623 pubmed publisher
    ..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. ..
  14. Li Q, Su Y, Wang H, Li L, Wang Q, Bao L. Transmembrane segments prevent surface expression of sodium channel Nav1.8 and promote calnexin-dependent channel degradation. J Biol Chem. 2010;285:32977-87 pubmed publisher
    ..Thus our results reveal a critical role and mechanism of transmembrane segments in surface expression and degradation of Na(v)1.8. ..
  15. Yang F, Sun W, Yang Y, Wang Y, Li C, Fu H, et al. SDF1-CXCR4 signaling contributes to persistent pain and hypersensitivity via regulating excitability of primary nociceptive neurons: involvement of ERK-dependent Nav1.8 up-regulation. J Neuroinflammation. 2015;12:219 pubmed publisher
    ..8 up-regulation, leading to hyperexcitability of tonic type of the primary nociceptor cells and development and maintenance of persistent spontaneous pain and hypersensitivity. ..
  16. Yamaoka K, Inoue M, Miyazaki K, Hirama M, Kondo C, Kinoshita E, et al. Synthetic ciguatoxins selectively activate Nav1.8-derived chimeric sodium channels expressed in HEK293 cells. J Biol Chem. 2009;284:7597-605 pubmed publisher
    ..4 and Na(v)1.8. Chimeras containing the N-terminal half of Na(v)1.8 exhibited a large response similar to wild-type Na(v)1.8, indicating that the region conferring high sensitivity to ciguatoxin action is located in the D1 or D2 domains. ..
  17. Zhang L, Liu H, Wang D. [Nav1.8 and Nav1.9 mRNA expression in rat trigeminal ganglion at different interval after molar extraction]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2009;44:301-3 pubmed
    ..8 and Nav1.9 mRNA, indicating the participation of sodium channels in regulations of peripheral tissue pain after molar extraction. ..
  18. Thun J, Persson A, Fried K. Differential expression of neuronal voltage-gated sodium channel mRNAs during the development of the rat trigeminal ganglion. Brain Res. 2009;1269:11-22 pubmed publisher
    ..They also raise the possibility that different facial regions could differ in the ability to transmit sensory signals during early life. ..
  19. Ye P, Hua L, Jiao Y, Li Z, Qin S, Fu J, et al. Functional up-regulation of Nav1.8 sodium channel on dorsal root ganglia neurons contributes to the induction of scorpion sting pain. Acta Biochim Biophys Sin (Shanghai). 2016;48:132-44 pubmed publisher
    ..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. ..
  20. Farmer C, Smith K, Docherty R. Low concentrations of tetrodotoxin interact with tetrodotoxin-resistant voltage-gated sodium channels. Br J Pharmacol. 2008;155:34-43 pubmed publisher
    ..We conclude that TTX binds to the TTXR VGSC at low concentrations, without blocking it. This appears to be the first demonstration of a clear distinction between binding affinity and blocking potency of a channel-blocking agent. ..
  21. Oaklander A, Belzberg A. Unilateral nerve injury down-regulates mRNA for Na+ channel SCN10A bilaterally in rat dorsal root ganglia. Brain Res Mol Brain Res. 1997;52:162-5 pubmed
    ..We report that nerve injury depress levels of SCN10A-specific mRNA in contralateral as well as ipsilateral dorsal root ganglia of rats, suggesting a possible ..
  22. Qu R, Tao J, Wang Y, Zhou Y, Wu G, Xiao Y, et al. Neonatal colonic inflammation sensitizes voltage-gated Na(+) channels via upregulation of cystathionine ?-synthetase expression in rat primary sensory neurons. Am J Physiol Gastrointest Liver Physiol. 2013;304:G763-72 pubmed publisher
  23. Chambers J, Zhao J, Terracciano C, Bezzina C, Zhang W, Kaba R, et al. Genetic variation in SCN10A influences cardiac conduction. Nat Genet. 2010;42:149-52 pubmed publisher
    ..We identified association of a nonsynonymous SNP, rs6795970, in SCN10A (P = 2.8 x 10(-15)) with PR interval, a marker of cardiac atrioventricular conduction...
  24. Medvedeva Y, Kim M, Schnizler K, Usachev Y. Functional tetrodotoxin-resistant Na(+) channels are expressed presynaptically in rat dorsal root ganglia neurons. Neuroscience. 2009;159:559-69 pubmed publisher
  25. Schirmeyer J, Szafranski K, Leipold E, Mawrin C, Platzer M, Heinemann S. Exon 11 skipping of SCN10A coding for voltage-gated sodium channels in dorsal root ganglia. Channels (Austin). 2014;8:210-5 pubmed
    The voltage-gated sodium channel Na(V)1.8 (encoded by SCN10A) is predominantly expressed in dorsal root ganglia(DRG) and plays a critical role in pain perception...
  26. Hu D, Barajas Martinez H, Pfeiffer R, Dezi F, Pfeiffer J, Buch T, et al. Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome. J Am Coll Cardiol. 2014;64:66-79 pubmed publisher
    ..Less than 35% of BrS probands have genetically identified pathogenic variants. Recent evidence has implicated SCN10A, a neuronal sodium channel gene encoding Nav1.8, in the electrical function of the heart...
  27. Choi J, Dib Hajj S, Waxman S. Differential slow inactivation and use-dependent inhibition of Nav1.8 channels contribute to distinct firing properties in IB4+ and IB4- DRG neurons. J Neurophysiol. 2007;97:1258-65 pubmed
    ..8 current in these two DRG subpopulations, which results from their different rate of entry into and recovery from the slow inactivation state, contributes to functional differences between these two neuronal populations. ..
  28. Vijayaragavan K, Acharfi S, Chahine M. The C-terminal region as a modulator of rNa(v)1.7 and rNa(v)1.8 expression levels. FEBS Lett. 2004;559:39-44 pubmed
    ..7 C-terminus expressed 3.2-fold and 4.8-fold higher peak current densities, respectively, than parent rNa(v)1.8 channels. We conclude that the two Na(+) channels may have different endoplasmic reticulum processing signals. ..
  29. Belkouch M, Dansereau M, T├ętreault P, Biet M, Beaudet N, Dumaine R, et al. Functional up-regulation of Nav1.8 sodium channel in A? afferent fibers subjected to chronic peripheral inflammation. J Neuroinflammation. 2014;11:45 pubmed publisher
    ..Collectively, these findings support a key role for Na(v)1.8 in controlling the excitability of A?-fibers and its potential contribution to the development of mechanical allodynia under persistent inflammation. ..
  30. Kerr N, Holmes F, Wynick D. Novel isoforms of the sodium channels Nav1.8 and Nav1.5 are produced by a conserved mechanism in mouse and rat. J Biol Chem. 2004;279:24826-33 pubmed
    ..1 kilobases of genomic DNA spanning exons 16-18 of Scn10a. A novel cDNA isoform was identified, designated Na(v)1...
  31. Li G, Liu X, Du J, Chen J, She F, Wu C, et al. Positive shift of Nav1.8 current inactivation curve in injured neurons causes neuropathic pain following chronic constriction injury. Mol Med Rep. 2015;12:3583-3590 pubmed publisher
  32. Shao D, Baker M, Abrahamsen B, Rugiero F, Malik Hall M, Poon W, et al. A multi PDZ-domain protein Pdzd2 contributes to functional expression of sensory neuron-specific sodium channel Na(V)1.8. Mol Cell Neurosci. 2009;42:219-25 pubmed publisher
    ..8, in dorsal root ganglia of Pdzd2-deficient mice. These findings reveal that Pdzd2 and p11 play collaborative roles in regulation of Na(V)1.8 expression in sensory neurons. ..
  33. Pan H, Liu B, Lin W, Zhang Y. Modulation of Nav1.8 by Lysophosphatidic Acid in the Induction of Bone Cancer Pain. Neurosci Bull. 2016;32:445-54 pubmed publisher
    ..Overall, we demonstrated the modulation of Nav1.8 by LPA in DRG neurons, and that this probably underlies the peripheral mechanism by which bone cancer pain is induced. ..
  34. Yue J, Wang R, Yu J, Tang Y, Hou W, Lou G, et al. Histamine upregulates Nav1.8 expression in primary afferent neurons via H2 receptors: involvement in neuropathic pain. CNS Neurosci Ther. 2014;20:883-92 pubmed publisher
    ..8 expression in primary afferent neurons via H2 receptor-mediated pathway and thereby contributes to neuropathic pain. H2 receptor antagonists may potentially be used as analgesics for patients with neuropathic pain. ..
  35. Zhao R, Pei G, Cong R, Zhang H, Zang C, Tian T. PKC-NF-?B are involved in CCL2-induced Nav1.8 expression and channel function in dorsal root ganglion neurons. Biosci Rep. 2014;34: pubmed publisher
    ..05), and was reversed by treatment with INCB3344 and AEB071. PKC-NF-?B are involved in CCL2-induced elevation of Nav1.8 current density by promoting the phosphorylation of Nav1.8 and its expression. ..
  36. Sangameswaran L, Delgado S, Fish L, Koch B, Jakeman L, Stewart G, et al. Structure and function of a novel voltage-gated, tetrodotoxin-resistant sodium channel specific to sensory neurons. J Biol Chem. 1996;271:5953-6 pubmed
    ..Here, we report the cloning of the alpha-subunit of a novel, voltage-gated sodium channel (PN3) from rat DRG...
  37. Ramachandra R, McGrew S, Baxter J, Howard J, Elmslie K. NaV1.8 channels are expressed in large, as well as small, diameter sensory afferent neurons. Channels (Austin). 2013;7:34-7 pubmed publisher
    ..8 current are invariant with neuron size. These data add further support to the idea that NaV1.8 contributes to the electrical excitability of both nociceptive and non-nociceptive sensory neurons. ..
  38. Byers M, Westenbroek R. Odontoblasts in developing, mature and ageing rat teeth have multiple phenotypes that variably express all nine voltage-gated sodium channels. Arch Oral Biol. 2011;56:1199-220 pubmed publisher
    ..Our data reveal much greater complexity and niche-specific specialization for odontoblasts than previously demonstrated, with implications for tooth sensitivity. ..
  39. Zhao J, O Leary M, Chahine M. Regulation of Nav1.6 and Nav1.8 peripheral nerve Na+ channels by auxiliary ?-subunits. J Neurophysiol. 2011;106:608-19 pubmed publisher
    ..8, similar to that observed for wild-type ?(1)-subunits. The intracellular COOH-terminal domain of the ?(1)-subunit appeared to play an essential role in the regulation of Na(v)1.8 expression and gating. ..
  40. Denny J, Ritchie M, Crawford D, Schildcrout J, Ramirez A, Pulley J, et al. Identification of genomic predictors of atrioventricular conduction: using electronic medical records as a tool for genome science. Circulation. 2010;122:2016-21 pubmed publisher
    ..association studies in which selected community populations are used have identified genomic signals in SCN10A influencing PR duration...
  41. Zhang Z, Li Q, Liu C, Wang H, Wang Q, Bao L. The voltage-gated Na+ channel Nav1.8 contains an ER-retention/retrieval signal antagonized by the beta3 subunit. J Cell Sci. 2008;121:3243-52 pubmed publisher
    ..Thus, the beta3 subunit regulates surface expression of Na(v)1.8 by antagonizing its ER-retention/retrieval signal. These results reveal a novel mechanism for the effect of the Na(+) channel beta subunits on the alpha subunits. ..
  42. Hu S, Xiao Y, Zhu L, Li L, Hu C, Jiang X, et al. Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats. Am J Physiol Gastrointest Liver Physiol. 2013;304:G311-21 pubmed publisher
    ..8 at protein levels, thus identifying a specific molecular mechanism underlying chronic visceral pain and sensitization in patients with IBS. ..
  43. Esmaeili A, Akhavan A, Bouzari M, Mousavi S, Torabinia N, Adibi S. Temporal expression pattern of sodium channel Nav 1.8 messenger RNA in pulpitis. Int Endod J. 2011;44:499-504 pubmed publisher
    ..As Nav 1.8 has been considered to have a role in neuropathic pain, its expression within dental pulp may contribute to the pathophysiology of tooth pain. ..
  44. Schirmeyer J, Szafranski K, Leipold E, Mawrin C, Platzer M, Heinemann S. A subtle alternative splicing event of the Na(V)1.8 voltage-gated sodium channel is conserved in human, rat, and mouse. J Mol Neurosci. 2010;41:310-4 pubmed publisher
    The voltage-gated sodium channel subtype Na(V)1.8 (SCN10A) is exclusively expressed in dorsal root ganglia (DRG) and plays a critical role in pain perception...
  45. Liu C, Cummins T, Tyrrell L, Black J, Waxman S, Dib Hajj S. CAP-1A is a novel linker that binds clathrin and the voltage-gated sodium channel Na(v)1.8. Mol Cell Neurosci. 2005;28:636-49 pubmed
    ..CAP-1A thus is the first example of an adapter protein that links clathrin and a sodium channel and may regulate Na(v)1.8 channel density at the cell surface. ..
  46. Vijayaragavan K, Powell A, Kinghorn I, Chahine M. Role of auxiliary beta1-, beta2-, and beta3-subunits and their interaction with Na(v)1.8 voltage-gated sodium channel. Biochem Biophys Res Commun. 2004;319:531-40 pubmed
    ..The results in this study suggest that the functional behavior of Nav1.8 will vary depending on the type of beta-subunit that expressed under normal and disease states. ..