Regulation/modulation of sensory neuron sodium channels

Handbook of Experimental Pharmacology

Volumn 221, Issue , 2014, Pages 111-135

  Chahine, Mohamed ^a,b   O’Leary, Michael E ^c  

^a Centre de recherche Institut en santé mentale de Québec   (Canada)

^b UNIVERSITÉ LAVAL   (Canada)

^c Cooper Medical School of Rowan University ^*  (United States)

Author keywords

Dorsal root ganglion; NaV; Nociception; Pain; Protein kinase

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE; SODIUM CHANNEL; SODIUM CHANNEL NAV1.1; SODIUM CHANNEL NAV1.2; SODIUM CHANNEL NAV1.4; SODIUM CHANNEL NAV1.5; SODIUM CHANNEL NAV1.6; SODIUM CHANNEL NAV1.7; SODIUM CHANNEL NAV1.8; SODIUM CHANNEL NAV1.9; VOLTAGE GATED SODIUM CHANNEL; CYCLIC AMP DEPENDENT PROTEIN KINASE; PROTEIN KINASE C; SODIUM;

ARTICLE; DISEASE ASSOCIATION; ENZYME ACTIVATION; ENZYME ACTIVITY; GLYCOSYLATION; HUMAN; NERVE CELL PLASTICITY; NERVE EXCITABILITY; NEUROMODULATION; NEUROTRANSMISSION; NOCICEPTION; PAIN; PERIPHERAL NERVE INJURY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LIPID INTERACTION; PROTEIN PROCESSING; SENSORY NERVE CELL; SIGNAL TRANSDUCTION; SODIUM CURRENT; SPINAL GANGLION; ACTION POTENTIAL; ANIMAL; CHANNEL GATING; METABOLISM; PAIN RECEPTOR; PAIN THRESHOLD; PATHOPHYSIOLOGY; REVIEW;

ACTION POTENTIALS; ANIMALS; CYCLIC AMP-DEPENDENT PROTEIN KINASES; GANGLIA, SPINAL; GLYCOSYLATION; HUMANS; ION CHANNEL GATING; MITOGEN-ACTIVATED PROTEIN KINASES; NEURONAL PLASTICITY; NOCICEPTORS; PAIN; PAIN THRESHOLD; PROTEIN KINASE C; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION; SODIUM; VOLTAGE-GATED SODIUM CHANNELS;

EID: 84903907053     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/978-3-642-41588-3_6     Document Type: Article

References (184)

1. Akopian AN, Sivilotti L, Wood JN (1996) A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature 379:257–262
2. Akopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J, Smith A, Kerr BJ, McMahon SB, Boyce S, Hill R, Stanfa LC, Dickenson AH, Wood JN (1999) The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci 2:541–548
3. Albrecht PJ, Rice FL (2010) Role of small-fiber afferents in pain mechanisms with implications on diagnosis and treatment. Curr Pain Headache Rep 14:179–188
4. Aley KO, Messing RO, Mochly-Rosen D, Levine JD (2000) Chronic hypersensitivity for inflammatory nociceptor sensitization mediated by the epsilon isozyme of protein kinase C. J Neurosci 20:4680–4685
5. Amaya F, Decosterd I, Samad TA, Plumpton C, Tate S, Mannion RJ, Costigan M, Woolf CJ (2000) Diversity of expression of the sensory neuron-specific TTX-resistant voltage-gated sodium ion channels SNS and SNS2. Mol Cell Neurosci 15(4):331–342
6. Amaya F, Wang H, Costigan M, Allchorne AJ, Hatcher JP, Egerton J, Stean T, Morisset V, Grose D, Gunthorpe MJ, Chessell IP, Tate S, Green PJ, Woolf CJ (2006) The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci 26:12852–12860
7. Andreeva L, Rang HP (1993) Effect of bradykinin and prostaglandins on the release of calcitonin gene-related peptide-like immunoreactivity from the rat spinal cord in vitro. Br J Pharmacol 108:185–190
8. Azhderian EM, Hefner D, Lin CH, Kaczmarek LK, Forscher P (1994) Cyclic AMP modulates fast axonal transport in Aplysia bag cell neurons by increasing the probability of single organelle movement. Neuron 12:1223–1233
9. Battaini F (2001) Protein kinase C isoforms as therapeutic targets in nervous system disease states. Pharmacol Res 44:353–361
10. Bendahhou S, Cummins TR, Potts JF, Tong J, Agnew WS (1995) Serine-1321-independent regulation of the μ1 adult skeletal muscle Na+ channel by protein kinase C. Proc Natl Acad Sci U S A 92:12003–12007
11. Benn SC, Costigan M, Tate S, Fitzgerald M, Woolf CJ (2001) Developmental expression of the TTX-resistant voltage-gated sodium channels Nav1.8 (SNS) and Nav1.9 (SNS2) in primary sensory neurons. J Neurosci 21:6077–6085
12. Bennett E, Urcan MS, Tinkle SS, Koszowski AG, Levinson SR (1997) Contribution of sialic acid to the voltage dependence of sodium channel gating. A possible electrostatic mechanism. J Gen Physiol 109:327–343
13. Bhave G, Gereau RW (2004) Posttranslational mechanisms of peripheral sensitization. J Neurobiol 61:88–106
14. Black JA, Dib-Hajj S, McNabola K, Jeste S, Rizzo MA, Kocsis JD, Waxman SG (1996) Spinal sensory neurons express multiple sodium channel alpha-subunit mRNAs. Brain Res Mol Brain Res 43:117–131
15. Black JA, Cummins TR, Plumpton C, Chen YH, Hormuzdiar W, Clare JJ, Waxman SG (1999) Upregulation of a silent sodium channel after peripheral, but not central, nerve injury in DRG neurons. J Neurophysiol 82:2776–2785
16. Black JA, Liu S, Tanaka M, Cummins TR, Waxman SG (2004) Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain 108:237–247
17. Black JA, Nikolajsen L, Kroner K, Jensen TS, Waxman SG (2008) Multiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas. Ann Neurol 64:644–653
18. Blair NT, Bean BP (2002) Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potentials of nociceptive sensory neurons. J Neurosci 22:10277–10290
19. Blair NT, Bean BP (2003) Role of tetrodotoxin-resistant Na+ current slow inactivation in adaptation of action potential firing in small-diameter dorsal root ganglion neurons. J Neurosci 23:10338–10350
20. Bradbury EJ, Burnstock G, McMahon SB (1998) The expression of P2X3 purinoreceptors in sensory neurons: effects of axotomy and glial-derived neurotrophic factor. Mol Cell Neurosci 12:256–268
21. Burgess PR, Perl ER (1967) Myelinated afferent fibres responding specifically to noxious stimulation of the skin. J Physiol 190:541–562
22. Caffrey JM, Eng DL, Black JA, Waxman SG, Kocsis JD (1992) Three types of sodium channels in adult rat dorsal root ganglion neurons. Brain Res 592:283–297
23. Campbell JN, Meyer RA (2006) Mechanisms of neuropathic pain. Neuron 52:77–92
24. Cang CL, Zhang H, Zhang YQ, Zhao ZQ (2009) PKCepsilon-dependent potentiation of TTX-resistant Nav1.8 current by neurokinin-1 receptor activation in rat dorsal root ganglion neurons. Mol Pain 5:33
25. Cantrell AR, Ma JY, Scheuer T, Catterall WA (1996) Muscarinic modulation of sodium current by activation of protein kinase C in rat hippocampal neurons. Neuron 16:1019–1026
26. Cantrell AR, Scheuer T, Catterall WA (1999) Voltage-dependent neuromodulation of Na+ channels by D1-like dopamine receptors in rat hippocampal neurons. J Neurosci 19:5301–5310
27. Cantrell AR, Tibbs VC, Yu FH, Murphy BJ, Sharp EM, Qu Y, Catterall WA, Scheuer T (2002a) Molecular mechanism of convergent regulation of brain Na+ channels by protein kinase C and protein kinase A anchored to AKAP-15. Mol Cell Neurosci 21:63–80
28. Cantrell AR, Yu F, Sharp EM, Qu Y, Murphy BJ, Scheuer T, Catterall WA (2002b) Molecular mechanisms underlying convergent regulation of brain Na+ channels by protein kinase A and protein kinase C. J Neurosci, 713.17 [Ref type: Abstract]
29. Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D (1997) The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–824
30. Cesare P, Dekker LV, Sardini A, Parker PJ, McNaughton PA (1999) Specific involvement of PKC-ε in sensitization of the neuronal response to painful heat. Neuron 23:617–624
31. Chatelier A, Dahllund L, Eriksson A, Krupp J, ChahineM(2008) Biophysical properties of human Na v1.7 splice variants and their regulation by protein kinase A. J Neurophysiol 99:2241–2250
32. Chattopadhyay M, Mata M, Fink DJ (2008) Continuous delta-opioid receptor activation reduces neuronal voltage-gated sodium channel (NaV1.7) levels through activation of protein kinase C in painful diabetic neuropathy. J Neurosci 28:6652–6658
33. Chen TC, Law B, Kondratyuk T, Rossie S (1995) Identification of soluble protein phosphatases that dephosphorylate voltage-sensitive sodium channels in rat brain. J Biol Chem 270:7750–7756
34. Cheng JK, Ji RR (2008) Intracellular signaling in primary sensory neurons and persistent pain. Neurochem Res 33:1970–1978
35. Chong JA, Tapia-Ramirez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD, Mandel G (1995) REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 80:949–957
36. Costigan M, Scholz J, Woolf CJ (2009) Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 32:1–32
37. Cummins TR, Waxman SG (1997) Downregulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodotoxin-sensitive sodium current in small spinal sensory neurons after nerve injury. J Neurosci 17:3503–3514
38. Cummins TR, Howe JR, Waxman SG (1998) Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the hNE/PN1 sodium channel. J Neurosci 18:9607–9619
39. Cummins TR, Dib-Hajj SD, Black JA, Akopian AN, Wood JN, Waxman SG (1999) A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons. J Neurosci 19:43
40. Cummins TR, Black JA, Dib-Hajj SD, Waxman SG (2000) Glial-derived neurotrophic factor upregulates expression of functional SNS and NaN sodium channels and their currents in axotomized dorsal root ganglion neurons. J Neurosci 20:8754–8761
41. Cummins TR, Sheets PL, Waxman SG (2007) The roles of sodium channels in nociception: implications for mechanisms of pain. Pain 131:243–257
42. d’Alcantara P, Cardenas LM, Swillens S, Scroggs RS (2002) Reduced transition between open and inactivated channel states underlies 5HT increased I(Na+) in rat nociceptors. Biophys J 83:5–21
43. Dang TX, McCleskey EW (1998) Ion channel selectivity through stepwise changes in binding affinity. J Gen Physiol 111:185–193
44. Dempsey EC, Newton AC, Mochly-Rosen D, Fields AP, Reyland ME, Insel PA, Messing RO (2000) Protein kinase C isozymes and the regulation of diverse cell responses. Am J Physiol 279:L429–L438
45. Dib-Hajj SD, Black JA, Cummins TR, Kenney AM, Kocsis JD, Waxman SG (1998a) Rescue of α-SNS sodium channel expression in small dorsal root ganglion neurons after axotomy by nerve growth factor in vivo. J Neurophysiol 79:2668–2676
46. Dib-Hajj SD, Tyrrell L, Black JA, Waxman SG (1998b) NaN, a novel voltage-gated Na channel, is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy. Proc Natl Acad Sci 95:8963–8968
47. Dib-Hajj SD, Tyrrell L, Cummins TR, Black JA, Wood PM, Waxman SG (1999) Two tetrodotoxin-resistant sodium channels in human dorsal root ganglion neurons. FEBS Lett 462:117–120
48. Dib-Hajj S, Black JA, Cummins TR, Waxman SG (2002) NaN/Nav1.9: a sodium channel with unique properties. Trends Neurosci 25:253–259
49. Dib-Hajj SD, Binshtok AM, Cummins TR, Jarvis MF, Samad T, Zimmermann K (2009) Voltagegated sodium channels in pain states: role in pathophysiology and targets for treatment. Brain Res Rev 60:65–83
50. Djouhri L, Fang X, Okuse K, Wood JN, Berry CM, Lawson SN (2003) The TTX-resistant sodium channel Nav1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons. J Physiol 550:739–752
51. Dong X, Han S, Zylka MJ, Simon MI, Anderson DJ (2001) A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 106:619–632
52. Dubin AE, Patapoutian A (2010) Nociceptors: the sensors of the pain pathway. J Clin Invest 120:3760–3772
53. Elkabes S, Dreyfus CF, Schaar DG, Black IB (1994) Embryonic sensory development: local expression of neurotrophin-3 and target expression of nerve growth factor. J Comp Neurol 341:204–213
54. Elliott AA, Elliott JR (1993) Characterization of TTX-sensitive and TTX-resistant sodium currents in small cells from adult rat dorsal root ganglia. J Physiol 463:39–56
55. England S, Bevan S, Docherty RJ (1996) PGE2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade. J Physiol 495:429–440
56. Fang X, Djouhri L, Black JA, Dib-Hajj SD, Waxman SG, Lawson SN (2002) The presence and role of the tetrodotoxin-resistant sodium channel Na(v)1.9 (NaN) in nociceptive primary afferent neurons. J Neurosci 22:7425–7433
57. Fang X, Djouhri L, McMullan S, Berry C, Waxman SG, Okuse K, Lawson SN (2006) Intense isolectin-B4 binding in rat dorsal root ganglion neurons distinguishes C-fiber nociceptors with broad action potentials and high Nav1.9 expression. J Neurosci 26:7281–7292
58. Fitzgerald EM, Okuse K, Wood JN, Dolphin AC, Moss SJ (1999) cAMP-dependent phosphorylation of the tetrodotoxin-resistant voltage-dependent sodium channel SNS. J Physiol 516:433–446
59. Fornaro M, Lee JM, Raimondo S, Nicolino S, Geuna S, Giacobini-Robecchi M (2008) Neuronal intermediate filament expression in rat dorsal root ganglia sensory neurons: an in vivo and in vitro study. Neuroscience 153:1153–1163
60. Fuchs E, Cleveland DW (1998) A structural scaffolding of intermediate filaments in health and disease. Science 279:514–519
61. Godoy CMG, Cukierman S (1994) Diacylglycerol-induced activation of protein kinase C attenuates Na+ currents by enhancing inactivation from the closed state. Pflugers Arch 429:245–252
62. Gold MS (1999) Tetrodotoxin-resistant Na+ currents and inflammatory hyperalgesia. Proc Natl Acad Sci U S A 96:7645–7649
63. Gold MS, Dastmalchi S, Levine JD (1996a) Co-expression of nociceptor properties in dorsal root ganglion neurons from the adult rat in vitro. Neuroscience 71:265–275
64. Gold MS, Reichling DB, Shuster MJ, Levine JD (1996b) Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors. Proc Natl Acad Sci U S A 93:1108–1112
65. Gold MS, Levine JD, Correa AM (1998) Modulation of TTX-R INa by PKC and PKA and their role in PGE2-induced sensitization of rat sensory neurons in vitro. J Neurosci 18:10345–10355
66. Goldstein ME, House SB, Gainer H (1991) NF-L and peripherin immunoreactivities define distinct classes of rat sensory ganglion cells. J Neurosci Res 30:92–104
67. Guo A, Vulchanova L, Wang J, Li X, Elde R (1999) Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Eur J Neurosci 11:946–958
68. Harper AA, Lawson SN (1985a) Conduction velocity is related to morphological cell type in rat dorsal root ganglion neurones. J Physiol 359:31–46
69. Harper AA, Lawson SN (1985b) Electrical properties of rat dorsal root ganglion neurones with different peripheral nerve conduction velocities. J Physiol 359(47–63):47–63
70. He XH, Zang Y, Chen X, Pang RP, Xu JT, Zhou X, Wei XH, Li YY, Xin WJ, Qin ZH, Liu XG (2010) TNF-alpha contributes to up-regulation of Nav1.3 and Nav1.8 in DRG neurons following motor fiber injury. Pain 151:266–279
71. Herzog RI, Cummins TR, Waxman SG (2001) Persistent TTX-resistant Na+ current affects resting potential and response to depolarization in simulated spinal sensory neurons. J Neurophysiol 86:1351–1364
72. Ho C, O’Leary ME (2011) Single-cell analysis of sodium channel expression in dorsal root ganglion neurons. Mol Cell Neurosci 46:159–166
73. Ho C, Zhao J, Malinowski S, Chahine M, O’Leary ME (2012) Differential expression of sodium channel beta subunits in dorsal root ganglion sensory neurons. J Biol Chem 287:15044–15053
74. Hoffman PN, Thompson GW, Griffin JW, Price DL (1985) Changes in neurofilament transport coincide temporally with alterations in the caliber of axons in regenerating motor fibers. J Cell Biol 101:1332–1340
75. Hucho T, Levine JD (2007) Signaling pathways in sensitization: toward a nociceptor cell biology. Neuron 55:365–376
76. Hudmon A, Choi JS, Tyrrell L, Black JA, Rush AM, Waxman SG, Dib-Hajj SD (2008) Phosphorylation of sodium channel Na(v)1.8 by p38 mitogen-activated protein kinase increases current density in dorsal root ganglion neurons. J Neurosci 28:3190–3201
77. Igwe OJ, Chronwall BM (2001) Hyperalgesia induced by peripheral inflammation is mediated by protein kinase C βII isozyme in the rat spinal cord. Neuroscience 104:875–890
78. Ikeda M, Yoshida S, Kadoi J, Nakano Y, Mastumoto S (2005) The effect of PKC activity on the TTX-R sodium currents from rat nodose ganglion neurons. Life Sci 78:47–53
79. Ji RR, Strichartz G (2004) Cell signaling and the genesis of neuropathic pain. Sci STKE 2004: reE14
80. Jin X, Gereau RW IV (2006) Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-α. J Neurosci 26:246–255
81. Jin SX, Zhuang ZY, Woolf CJ, Ji RR (2003) p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci 23:4017–4022
82. Joseph EK, Levine JD (2010) Hyperalgesic priming is restricted to isolectin B4-positive nociceptors. Neuroscience 169:431–435
83. Julius D, Basbaum AI (2001) Molecular mechanisms of nociception. Nature 413:203–210
84. Kawabata A (2011) Prostaglandin E2 and pain–an update. Biol Pharm Bull 34:1170–1173
85. Khasar SG, Lin YH, Martin A, Dadgar J, McMahon T, Wang D, Hundle B, Aley KO, Isenberg W, McCarter G, Green PG, Hodge CW, Levine JD, Messing RO (1999) A novel nociceptor signaling pathway revealed in protein kinase C ε mutant mice. Neuron 24:253–260
86. Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 1802:396–405
87. Kim CH, Oh Y, Chung JM, Chung K (2002) Changes in three subtypes of tetrodotoxin sensitive sodium channel expression in the axotomized dorsal root ganglion in the rat. Neurosci Lett 323:125–128
88. Kondratyuk T, Rossie S (1997) Depolarization of rat brain synaptosomes increases phosphorylation of voltage-sensitive sodium channels. J Biol Chem 272:16978–16983
89. Kostyuk PG, Veselovsky NS, Tsyndrenko AY (1981) Ionic currents in the somatic membrane of rat dorsal root ganglion neurons-I. Sodium currents. Neuroscience 6:2423–2430
90. Kruger L, Light AR, Schweizer FE (2003) Axonal terminals of sensory neurons and their morphological diversity. J Neurocytol 32:205–216
91. Lai J, Porreca F, Hunter JC, Gold MS (2004) Voltage-gated sodium channels and hyperalgesia. Annu Rev Pharmacol Toxicol 44:371–397
92. Lawson SN (2002) Phenotype and function of somatic primary afferent nociceptive neurones with C-, Adelta- or Aalpha/beta-fibres. Exp Physiol 87:239–244
93. Lawson SN, Perry MJ, Prabhakar E, McCarthy PW (1993) Primary sensory neurones: neurofilament, neuropeptides, and conduction velocity. Brain Res Bull 30:239–243
94. Lee KH, Chung K, Chung JM, Coggeshall RE (1986) Correlation of cell body size, axon size, and signal conduction velocity for individually labelled dorsal root ganglion cells in the cat. J Comp Neurol 243:335–346
95. Lewis TS, Shapiro PS, Ahn NG (1998) Signal transduction through MAP kinase cascades. Adv Cancer Res 74:49–139
96. Li M, West JW, Lai Y, Scheuer T, Catterall WA (1992) Functional modulation of brain sodium channels by cAMP-dependent phosphorylation. Neuron 8:1151–1159
97. Li M, West JW, Numann R, Murphy BJ, Scheuer T, Catterall WA (1993) Convergent regulation of sodium channels by protein kinase C and cAMP-dependent protein kinase. Science 261:1439–1442
98. Liu M, Willmott NJ, Michael GJ, Priestley JV (2004) Differential pH and capsaicin responses of Griffonia simplicifolia IB4 (IB4)-positive and IB4-negative small sensory neurons. Neuroscience 127:659–672
99. Liu Q, Vrontou S, Rice FL, Zylka MJ, Dong X, Anderson DJ (2007) Molecular genetic visualization of a rare subset of unmyelinated sensory neurons that may detect gentle touch. Nat Neurosci 10:946–948
100. Lopshire JC, Nicol GD (1998) The cAMP transduction cascade mediates the prostaglandin E2 enhancement of the capsaicin-elicited current in rat sensory neurons: whole-cell and singlechannel studies. J Neurosci 18:6081–6092
101. Lunyak VV, Burgess R, Prefontaine GG, Nelson C, Sze S-H, Chenoweth J, Schwartz P, Pevzner PA, Glass C, Mandel G, Rosenfeld MG (2002) Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science 298:1747–1752
102. Maingret F, Coste B, Padilla F, Clerc N, Crest M, Korogod SM, Delmas P (2008) Inflammatory mediators increase Nav1.9 current and excitability in nociceptors through a coincident detection mechanism. J Gen Physiol 131:211–225
103. Martin WJ, Liu H, Wang H, Malmberg AB, Basbaum AI (1999) Inflammation-induced up-regulation of protein kinase Cγ immunoreactivity in rat spinal cord correlates with enhanced nociceptive processing. Neuroscience 88:1267–1274
104. Maurel P, Einheber S, Galinska J, Thaker P, Lam I, Rubin MB, Scherer SS, Murakami Y, Gutmann DH, Salzer JL (2007) Nectin-like proteins mediate axon Schwann cell interactions along the internode and are essential for myelination. J Cell Biol 178:861–874
105. McCleskey EW, Gold MS (1999) Ion channels of nociception. Annu Rev Physiol 61:835–856
106. Michael GJ, Priestley JV (1999) Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its downregulation by axotomy. J Neurosci 19:1844–1854
107. Mittmann T, Alzheimer C (1998) Muscarinic inhibition of persistent Na+ current in rat neocortical pyramidal neurons. J Neurophysiol 79:1579–1582
108. Moriyama T, Higashi T, Togashi K, Iida T, Segi E, Sugimoto Y, Tominaga T, Narumiya S, Tominaga M (2005) Sensitization of TRPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins. Mol Pain 1:3
109. Murphy BJ, Catterall WA (1992) Phosphorylation of purified rat brain Na+ channel reconstituted into phospholipid vesicles by protein kinase C. J Biol Chem 267:16129–16134
110. Murphy BJ, Rossie S, De Jongh KS, Catterall WA (1993) Identification of the sites of selective phosphorylation and dephosphorylation of the rat brain Na+ channel α subunit by cAMPdependent protein kinase and phosphoprotein phosphatases. J Biol Chem 268:27355–27362
111. Murray KT, Hu NN, Daw JR, Shin HG, Watson MT, Mashburn AB, George AL Jr (1997) Functional effects of protein kinase C activation on the human cardiac Na+ channel. Circ Res 80:370–376
112. Nassar MA, Stirling LC, Forlani G, Baker MD, Matthews EA, Dickenson AH, Wood JN (2004) Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci U S A 101:12706–12711
113. Nicol GD, Cui M (1994) Enhancement by prostaglandin E2 of bradykinin activation of embryonic rat sensory neurones. J Physiol 480(Pt 3):485–492
114. Novakovic SD, Tzoumaka E, McGivern JG, Haraguchi M, Sangameswaran L, Gogas KR, Eglen RM, Hunter JC (1998) Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuropathic conditions. J Neurosci 18:2174–2187
115. Numann R, Catterall WA, Scheuer T (1991) Functional modulation of brain sodium channels by protein kinase C phosphorylation. Science 254:115–118
116. Obata K, Noguchi K (2004) MAPK activation in nociceptive neurons and pain hypersensitivity. Life Sci 74:2643–2653
117. Obata K, Yamanaka H, Kobayashi K, Dai Y, Mizushima T, Katsura H, Fukuoka T, Tokunaga A, Noguchi K (2004) Role of mitogen-activated protein kinase activation in injured and intact primary afferent neurons for mechanical and heat hypersensitivity after spinal nerve ligation. J Neurosci 24:10211–10222
118. Ogata N, Tatebayashi H (1993) Kinetic analysis of two types of Na+ channels in rat dorsal root ganglia. J Physiol 466:9–37
119. Oida H, Namba T, Sugimoto Y, Ushikubi F, Ohishi H, Ichikawa A, Narumiya S (1995) In situ hybridization studies of prostacyclin receptor mRNA expression in various mouse organs. Br J Pharmacol 116:2828–2837
120. Ostman JA, Nassar MA, Wood JN, Baker MD (2008) GTP up-regulated persistent Na+ current and enhanced nociceptor excitability require NaV1.9. J Physiol 586:1077–1087
121. Parada CA, Yeh JJ, Reichling DB, Levine JD (2003) Transient attenuation of protein kinase Cepsilon can terminate a chronic hyperalgesic state in the rat. Neuroscience 120:219–226
122. Perl ER (1996) Cutaneous polymodal receptors: characteristics and plasticity. Prog Brain Res 113:21–37
123. Petho G, Reeh PW (2012) Sensory and signaling mechanisms of bradykinin, eicosanoids, plateletactivating factor, and nitric oxide in peripheral nociceptors. Physiol Rev 92:1699–1775
124. Petruska JC, Napaporn J, Johnson RD, Gu JG, Cooper BY (2000) Subclassified acutely dissociated cells of rat DRG: histochemistry and patterns of capsaicin-, proton-, and ATP-activated currents. J Neurophysiol 84:2365–2379
125. Petruska JC, Napaporn J, Johnson RD, Cooper BY (2002) Chemical responsiveness and histochemical phenotype of electrophysiologically classified cells of the adult rat dorsal root ganglion. Neuroscience 115:15–30
126. Price TJ, Flores CM (2007) Critical evaluation of the colocalization between calcitonin generelated peptide, substance P, transient receptor potential vanilloid subfamily type 1 immunoreactivities, and isolectin B4 binding in primary afferent neurons of the rat and mouse. J Pain 8:263–272
127. Priest BT, Murphy BA, Lindia JA, Diaz C, Abbadie C, Ritter AM, Liberator P, Iyer LM, Kash SF, Kohler MG, Kaczorowski GJ, MacIntyre DE, Martin WJ (2005) Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to sensory transmission and nociceptive behavior. Proc Natl Acad Sci U S A 102:9382–9387
128. Priestley JV, Michael GJ, Averill S, Liu M, Willmott N (2002) Regulation of nociceptive neurons by nerve growth factor and glial cell line derived neurotrophic factor. Can J Physiol Pharmacol 80:495–505
129. Qu Y, Rogers J, Tanada T, Scheuer T, Catterall WA (1994) Modulation of cardiac Na+ channels expressed in a mammalian cell line and in ventricular myocytes by protein kinase C. Proc Natl Acad Sci U S A 91:3289–3293
130. Raymond CK, Castle J, Garrett-Engele P, Armour CD, Kan Z, Tsinoremas N, Johnson JM (2004) Expression of alternatively spliced sodium channel α-subnit genes: unique splicing patterns are observed in dorsal root ganglia. J Biol Chem 279:46234–46241
131. Reichling DB, Levine JD (2009) Critical role of nociceptor plasticity in chronic pain. Trends Neurosci 32:611–618
132. Renganathan M, Cummins TR, Hormuzdiar WN, Waxman SG (2000) alpha-SNS produces the slow TTX-resistant sodium current in large cutaneous afferent DRG neurons. J Neurophysiol 84:710–718
133. Renganathan M, Cummins TR, Waxman SG (2001) Contribution of Na(v)1.8 sodium channels to action potential electrogenesis in DRG neurons. J Neurophysiol 86:629–640
134. Ringkamp MMRA (2009) Physiology of nociceptors. In: Basbaum AIBMC (ed) Science of pain. Elsevier, pp 97–114
135. Rizzo MA, Kocsis JD, Waxman SG (1995) Selective loss of slow and enhancement of fast Na+ currents in cutaneous afferent dorsal root ganglion neurones following axotomy. Neurobiol Dis 2:87–96
136. Roy ML, Narahashi T (1992) Differential properties of tetrodotoxin-sensitive and tetrodotoxinresistant sodium channels in rat dorsal root ganglion neurons. J Neurosci 12:2104–2111
137. Rush AM, Waxman SG (2004) PGE(2) increases the tetrodotoxin-resistant Na(v)1.9 sodium current in mouse DRG neurons via G-proteins. Brain Res 1023:264–271
138. Rush AM, Brau ME, Elliott AA, Elliott JR (1998) Electrophysiological properties of sodium current subtypes in small cells from adult rat dorsal root ganglia. J Physiol 511:771–789
139. Rush AM, Cummins TR, Waxman SG (2007) Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. J Physiol 579:1–14
140. Sachs D, Villarreal C, Cunha F, Parada C, Ferreira S (2009) The role of PKA and PKCepsilon pathways in prostaglandin E2-mediated hypernociception. Br J Pharmacol 156:826–834
141. Sampo B, Tricaud N, Leveque C, Seagar M, Couraud F, Dargent B (2000) Direct interaction between synaptotagmin and the intracellular loop I-II of neuronal voltage-sensitive sodium channels. Proc Natl Acad Sci U S A 97:3666–3671
142. Sangameswaran L, Delgado SG, Fish LM, Koch BD, Jakeman LB, Stewart GR, Sze P, Hunter JC, Eglen RM, Herman RC (1996) Structure and function of a novel voltage-gated, tetrodotoxinresistant sodium channel specific to sensory neurons. J Biol Chem 271:5953–5956
143. Sangameswaran L, Fish LM, Koch BD, Rabert DK, Delgado SG, Ilnicka M, Jakeman LB, Novakovic S, Wong K, Sze P, Tzoumaka E, Stewart GR, Herman RC, Chan H, Eglen RM, Hunter JC (1997) A novel tetrodotoxin-sensitive, voltage-gated sodium channel expressed in rat and human dorsal root ganglia. J Biol Chem 272:14805–14809
144. Schild JH, Kunze DL (1997) Experimental and modeling study of Na+ current heterogeneity in rat nodose neurons and its impact on neuronal discharge. J Neurophysiol 78:3198–3209
145. Schmidt JW, Catterall WA (1986) Biosynthesis and processing of the α subunit of the voltagesensitive sodium channel in rat brain neurons. Cell 46:437–444
146. Schreibmayer W, Dascal N, Lotan I, Wallner M, Weigl L (1991) Molecular mechanism of protein kinase C modulation of sodium channel α-subunits expressed in Xenopus oocytes. FEBS Lett 291:341–344
147. Schreibmayer W, Frohnwieser B, Dascal N, Platzer D, Spreitzer B, Zechner R, Kallen RG, Lester HA (1994) β-adrenergic modulation of currents produced by rat cardiac Na+ channels expressed in Xenopus laevis oocytes. Receptors Channels 2:339–350
148. Seger R, Krebs EG (1995) The MAPK signaling cascade. FASEB J 9:726–735
149. Smith RD, Goldin AL (1992) Protein kinase A phosphorylation enhances sodium channel currents in Xenopus oocytes. Am J Physiol 263:C660–C666
150. Smith RD, Goldin AL (1996) Phosphorylation of brain sodium channels in the I-II linker modulates channel function in Xenopus oocytes. J Neurosci 16:1965–1974
151. Smith MR, Goldin AL (1997) Interaction between the sodium channel inactivation linker and domain III S4-S5. Biophys J 73:1885–1895
152. Smith RD, Goldin AL (2000) Potentiation of rat brain sodium channel currents by PKA in Xenopus oocytes involves the I-II linker. Am J Physiol 278:C638–C645
153. Snider WD, McMahon SB (1998) Tackling pain at the source: new ideas about nociceptors. Neuron 20:629–632
154. Spiegel I, Adamsky K, Eshed Y, Milo R, Sabanay H, Sarig-Nadir O, Horresh I, Scherer SS, Rasband MN, Peles E (2007) A central role for Necl4 (SynCAM4) in Schwann cell-axon interaction and myelination. Nat Neurosci 10:861–869
155. Stamboulian S, Choi JS, Ahn HS, Chang YW, Tyrrell L, Black JA, Waxman SG, Dib-Hajj SD (2010) ERK1/2 mitogen-activated protein kinase phosphorylates sodium channel Na(v)1.7 and alters its gating properties. J Neurosci 30:1637–1647
156. Stucky CL, Lewin GR (1999) Isolectin B(4)-positive and -negative nociceptors are functionally distinct. J Neurosci 19:6497–6505
157. Sugimoto Y, Shigemoto R, Namba T, Negishi M, Mizuno N, Narumiya S, Ichikawa A (1994) Distribution of the messenger RNA for the prostaglandin E receptor subtype EP3 in the mouse nervous system. Neuroscience 62:919–928
158. Tate S, Benn S, Hick C, Trezise D, John V, Mannion RJ, Costigan M, Plumpton C, Grose D, Gladwell Z, Kendall G, Dale K, Bountra C, Woolf CJ (1998) Two sodium channels contribute to the TTX-R sodium current in primary sensory neurons. Nat Neurosci 1:653–655
159. Toledo-Aral JJ, Moss BL, He ZJ, Koszowski AG, Whisenand T, Levinson SR, Wolf JJ, Silos-Santiago I, Halegoua S, Mandel G (1997) Identification of PN1, a predominant voltage-dependent sodium channel expressed principally in peripheral neurons. Proc Natl Acad Sci U S A 94:1527–1532
160. Tripathi PK, Trujillo L, Cardenas CA, Cardenas CG, de Armendi AJ, Scroggs RS (2006) Analysis of the variation in use-dependent inactivation of high-threshold tetrodotoxin-resistant sodium currents recorded from rat sensory neurons. Neuroscience 143:923–938
161. Tyrrell L, Renganathan M, Dib-Hajj SD, Waxman SG (2001) Glycosylation alters steady-state inactivation of sodium channel Nav1.9/NaN in dorsal root ganglion neurons and is developmentally regulated. J Neurosci 21:9629–9637
162. Vanoye CG, Kunic JD, Ehring GR, George AL Jr (2013) Mechanism of sodium channel NaV1.9 potentiation by G-protein signaling. J Gen Physiol 141:193–202
163. Vasko MR, Campbell WB, Waite KJ (1994) Prostaglandin E2 enhances bradykinin-stimulated release of neuropeptides from rat sensory neurons in culture. J Neurosci 14:4987–4997
164. Vijayaragavan K, O’Leary ME, Chahine M (2001) Gating properties of Na(v)1.7 and Na(v)1.8 peripheral nerve sodium channels. J Neurosci 21:7909–7918
165. Vijayaragavan K, Boutjdir M, Chahine M (2004) Modulation of nav1.7 and nav1.8 peripheral nerve sodium channels by protein kinase a and protein kinase C. J Neurophysiol 91:1556–1569
166. Villarreal CF, Sachs D, Cunha FQ, Parada CA, Ferreira SH (2005) The role of Na(V)1.8 sodium channel in the maintenance of chronic inflammatory hypernociception. Neurosci Lett 386:72–77
167. Waddell PJ, Lawson SN (1990) Electrophysiological properties of subpopulations of rat dorsal root ganglion neurons in vitro. Neuroscience 36:811–822
168. Waxman SG, Kocsis JD, Black JA (1994) Type III sodium channel mRNA is expressed in embryonic but not adult spinal sensory neurons, and is reexpressed following axotomy. J Neurophysiol 72:466–470
169. West JW, Numann R, Murphy BJ, Scheuer T, Catterall WA (1991) A phosphorylation site in the Na+ channel required for modulation by protein kinase C. Science 254:866–868
170. Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79:143–180
171. Wittmack EK, Rush AM, Hudmon A, Waxman SG, Dib-Hajj SD (2005) Voltage-gated sodium channel Nav1.6 is modulated by p38 mitogen-activated protein kinase. J Neurosci 25:6621–6630
172. Woolf CJ, CostiganM(1999) Transcriptional and posttranslational plasticity and the generation of inflammatory pain. Proc Natl Acad Sci U S A 96:7723–7730
173. Woolf CJ, Ma Q (2007) Nociceptors–noxious stimulus detectors. Neuron 55:353–364
174. Wright DE, Snider WD (1996) Focal expression of glial cell line-derived neurotrophic factor in developing mouse limb bud. Cell Tissue Res 286:209–217
175. Xu JT, Xin WJ, Wei XH, Wu CY, Ge YX, Liu YL, Zang Y, Zhang T, Li YY, Liu XG (2007) p38 activation in uninjured primary afferent neurons and in spinal microglia contributes to the development of neuropathic pain induced by selective motor fiber injury. Exp Neurol 204:355–365
176. Yoshida S, Matsuda Y (1979) Studies on sensory neurons of the mouse with intracellularrecording and horseradish peroxidase-injection techniques. J Neurophysiol 42:1134–1145
177. Zelano J, Plantman S, Hailer NP, Cullheim S (2009) Altered expression of nectin-like adhesion molecules in the peripheral nerve after sciatic nerve transection. Neurosci Lett 449:28–33
178. Zhang H, Cang CL, Kawasaki Y, Liang LL, Zhang YQ, Ji RR, Zhao ZQ (2007) Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCepsilon: a novel pathway for heat hyperalgesia. J Neurosci 27:12067–12077
179. Zhao J, O’Leary ME, Chahine M (2011) Regulation of Nav1.6 and Nav1.8 peripheral nerve Na+ channels by auxiliary {beta}-subunits. J Neurophysiol 106:608–619
180. Zheng T, Kakimura J, Matsutomi T, Nakamoto C, Ogata N (2007) Prostaglandin E2 has no effect on two components of tetrodotoxin-resistant Na+ current in mouse dorsal root ganglion. J Pharmacol Sci 103:93–102
181. Zhou J, Yi J, Hu NN, George AL Jr, Murray KT (2000) Activation of protein kinase A modulates trafficking of the human cardiac sodium channel in Xenopus oocytes. Circ Res 87:33–38
182. Zhou J, Shin HG, Yi J, Shen W, Williams CP, Murray KT (2002) Phosphorylation and putative ER retention signals are required for protein kinase A-mediated potentiation of cardiac sodium current. Circ Res 91:540–546
183. Zwick M, Davis BM, Woodbury CJ, Burkett JN, Koerber HR, Simpson JF, Albers KM (2002) Glial cell line-derived neurotrophic factor is a survival factor for isolectin B4-positive, but not vanilloid receptor 1-positive, neurons in the mouse. J Neurosci 22:4057–4065
184. Zylka MJ, Rice FL, Anderson DJ (2005) Topographically distinct epidermal nociceptive circuits revealed by axonal tracers targeted to Mrgprd. Neuron 45:17–25