Sodium channels and nociception: recent concepts and therapeutic opportunities

Current Opinion in Pharmacology

Volumn 8, Issue 1, 2008, Pages 50-56

  Krafte, Douglas S ^a   Bannon, Anthony W ^a  

^a Icagen Inc   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

A 803467; ANTISENSE OLIGONUCLEOTIDE; CARBAMAZEPINE; CDA 54; DULOXETINE; ENFLURANE; GABAPENTIN; LIDOCAINE; M 58373; PREGABALIN; RALFINAMIDE; SMALL INTERFERING RNA; SODIUM CHANNEL; SODIUM CHANNEL AFFECTING AGENT; SODIUM CHANNEL BLOCKING AGENT; TRICYCLIC ANTIDEPRESSANT AGENT; UNCLASSIFIED DRUG; VOLTAGE GATED SODIUM CHANNEL;

ANALGESIA; ATAXIA; BLOOD BRAIN BARRIER; CONGENITAL ANALGESIA; DIZZINESS; DRUG APPROVAL; DRUG EFFICACY; DRUG INDICATION; DRUG STRUCTURE; DRUG TARGETING; EXPERIMENTAL MODEL; GENE MUTATION; HUMAN; MEMBRANE PERMEABILITY; NEUROLOGIC DISEASE; NEUROPATHIC PAIN; NOCICEPTION; NONHUMAN; PRIORITY JOURNAL; REVIEW; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; UNITED STATES;

ANIMALS; HUMANS; NERVE TISSUE PROTEINS; NEUROPEPTIDES; PAIN; PERIPHERAL NERVOUS SYSTEM; SODIUM CHANNEL BLOCKERS; SODIUM CHANNELS; TETRODOTOXIN;

EID: 38649130197     PISSN: 14714892     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coph.2007.09.007     Document Type: Review

References (51)

1. Kyle D.J., and Ilyin V.I. Sodium channel blockers. J Med Chem 50 (2007) 2583-2588
2. Priest B.T., and Kaczorowski G.J. Blocking sodium channels to treat neuropathic pain. Expert Opin Ther Targets 11 3 (2007) 291-306
3. Goldin A.L. Resurgence of sodium channel research. Annu Rev Physiol 63 (2001) 871-894
4. Suzuki H., Beckh S., Kubo H., Yahagi N., Ishida H., Kayano T., Noda M., and Numa S. Functional expression of cloned cDNA encoding sodium channel III. FEBS Lett 228 1 (1988) 195-200
5. Waxman S.G., Kocsis J.D., and Black J.A. Type III sodium channel mRNA is expressed in embryonic, but not adult spinal sensory neurons, and is reexpressed following axotomy. J Neurophysiol 72 1 (1994) 466-470
6. Dib-Hajj S.D., Fjell J., Cummins T.R., Zheng Z., Fried K., LaMotte R., Black J.A., and Waxman S.G. Plasticity of sodium channel expression in DRG neurons in the chronic constriction injury model of neuropathic pain. Pain 83 (1999) 591-600
7. Garry E.M., Delaney A., Anderson H.A., Sirinathsinghji E.C., Clapp R.H., Martin W.J., Kinchington P.R., Krah D.L., Abbadie C., and Fleetwood-Walker S.M. Varicella zoster virus induces neuropathic changes in rat dorsal root ganglia and behavioral reflex sensitization that is attenuated by gabapentin or sodium channel blocking drugs. Pain 118 1-2 (2005) 97-111
8. Black J.A., Liu S., Tanaka M., Cummins T.R., and Waxman S.G. Changes in the expression of tetrodotoxin-sensitive sodium channels within dorsal root ganglia neurons in inflammatory pain. Pain 108 3 (2004) 237-247
9. Cummins T.R., and Waxman S.G. Down regulation of tetrodotoxin-resistant sodium currents and upregulation of a rapidly repriming tetrodoxin-sensitive sodium current in small spinal sensory neurons after nerve injury. J Neurosci 17 10 (1997) 3503-3514
10. D'Arcangelo G., Padiso K., Shepherd D., Brehm P., Halegoua S., and Mandel G. Neuronal growth factor regulation of two different sodium channel types through distinct signal transduction pathways. J Cell Biol 122 4 (1993) 915-921
11. Toledo-Aral J.J., Brehm P., Halegoua S., and Mandel G. A single pulse of nerve growth factor triggers long-term excitability through sodium channel gene induction. Neuron 14 3 (1995) 607-611
12. Toledo-Aral J.J., Moss B.L., Je Z.J., Koszowski A.G., Whisenand S., Levinson S.R., Wolff J.J., Silos-Santiago I., Halegoua S., and Mandel G. Identification of PN1, a predominant voltage-dependent sodium channel expressed principally in peripheral neurons. Proc Natl Acad Sci USA 94 4 (1997) 1527-1535
13. Klugbauer N., Lacinova L., Flockerzi V., and Hofmann F. Structure and functional expression of a new member of the tetrodotoxin-sensitive voltage-gated sodium channel family from human neuroendocrine cells. EMBO J 14 6 (1995) 1084-1090
14. Cummins T.R., Howe J.R., and Waxman S.G. Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the hNE/PN1 sodium channel. J Neurosci 18 23 (1998) 9607-9619
15. Sangameswaran L., Delgado S.G., Fish L.M., Koch B.D., Jakman L.B., Stewart G.R., Sze P., Hunter J.C., Eglen R.M., and Herman R.C. Structure and function of a novel voltage-gated, tetrodotoxin-resistant sodium channel specific to sensory neurons. J Biol Chem 271 11 (1996) 5953-5956
16. Renganathan M., Cummins T.R., and Waxman S.G. Contribution of Nav1.8 sodium channels to action potential electrogenesis in DRG neurons. J Neurophysiol 86 2 (2001) 629-640
17. Blair N.T., and Bean B.P. Role of tetrodotoxin (TTX)-sensitive Na current, TTX-resistant Na current and Ca current in the action potentials of nociceptive sensory neurons. J Neurosci 22 23 (2002) 10277-10290
18. Zimmerman K., Leffler A., Babes A., Cendan C.M., Carr R.W., Kobayashi J., Nau C., Wood J.N., and Reeh P.W. Sensory neuron sodium channel Nav1.8 is essential for pain at low temperatures. Nature 447 7146 (2007) 855-858. This study shows Nav1.8 becomes the sole functional sodium channel in nociceptive neurons upon cooling. This is due to a resistance to shifts in slow inactivation that are observed in other sodium channels and render them inactive at normal resting potentials in cooled neurons. These results indicate a crucial role for Nav1.8 in signaling cold-induced pain.
19. Dib-Hajj S.D., Tyrrell L., Black J.A., and Waxman S.G. NaN, a novel voltage-gated Na channel is expressed preferentially in peripheral sensory neurons and down-regulated after axotomy. Proc Natl Acad Sci USA 95 15 (1998) 8963-8968
20. Cummins T.R., Dib-Hajj S.D., Black J.A., Wood J.N., and Waxman S.G. A novel persistant tetrodotoxin-resistant sodium current in SNS null and wild-type small primary sensory neurons. J Neurosci 19 24 (1999) RC43
21. Hains B.C., Klein J.P., Saab C.Y., Craner M.J., Black J.A., and Waxman S.G. Upregulation of sodium channel Nav1.3 and functional involvement in neuronal hyperexcitability associated with central neuropathic pain after spinal cord injury. J Neurosci 23 26 (2003) 8881-8892
22. Hains B.C., Saab C.Y., Lo A.C., and Waxman S.G. Altered sodium channel expression in second-order spinal sensory neurons contributes to pain after peripheral nerve injury. J Neurosci 24 20 (2004) 4829-4832
23. Lindia J.A., Kohler M.G., Martin W.J., and Abbadie C. Relationship between sodium channel Nav1.3 expression and neuropathic pain behavior in rats. Pain 117 1-2 (2005) 145-153
24. Nassar M.A., Bayer M.D., Levato A., Ingram R., Mallucci G., McMahon S.B., and Wood J.N. Nerve injury induces robust allodynia and ectopic discharges in Nav1.3 null mutant mice. Mol Pain 2 (2006) 33
25. Nassar M.A., Stirling L.C., Forlani G., Baker M.D., Matthews E.A., Dickenson A.H., and Wood J.N. Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain. Proc Natl Acad Sci USA 101 34 (2004) 12706-12711
26. Cummins T.R., Dib-Hajj S.D., and Waxman S.G. Electrophysiological properties of mutant Nav1.7 sodium channels in painful inherited neuropathy. J Neurosci 24 38 (2004) 8232-8236
27. Fertleman C.R., Baker M.D., Parker K.A., Moffatt S., Elmslie F.V., Abrahamsen B., Ostman J., Klugbauer N., Wood J.N., Gardiner R.M., and Rees M. SCN9A mutations in paroxysmal extreme pain disorder: allelic variants underlie distinct channel defects and phenotypes. Neuron 52 5 (2006) 767-774
28. Cox J.J., Reimann F., Nicholas A.K., Thornton G., Roberts E., Springell K., Karbani G., Jafri H., Mannan J., Raashid Y., et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 4444 7121 (2006) 894-898. This is the first report that nonsense mutations in the SCN9A gene that encodes Nav1.7 channels led to loss-of-function of Nav1.7 and a human syndrome called Congenital Indifference to Pain. People with this syndrome are resistant to a wide variety of painful stimuli.
29. Goldberg Y.P., MacFarlane J., MacDonald M.L., Thompson J., Dube M.P., Mattice M., Fraser R., Young C., Hossain S., Pape T., et al. Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet 71 4 (2007) 311-319
30. Ahmad S., Dahllund L., Eriksson A.B., Hellgren D., Karlsson U., Lund P.E., Meijer I.A., Meury L., Mills L., Moody A., et al. A stop codon mutation in SCN9A causes lack of pain sensation. Hum Mol Genet 16 (2007) 2114-2121
31. Akopian A.N., Souslova V., England S., Okuse K., Ogata N., Ure J., Smith A., Kerr B.J., McMahon S.B., Boyce S., et al. The tetrodtoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci 2 6 (1999) 541-548
32. Kerr B.J., Souslova V., McMahon S.B., and Wood J.N. A role for the TTX-resistant sodium channel in NGF-induced hyperalgesia, but not neuropathic pain. Neuroreport 12 14 (2001) 3077-3080
33. Nassar M.A., Levato A., Stirling L.C., and Wood J.N. Neuropathic pain develops normally in mice lacking both Nav1.7 and Nav1.8. Mol Pain 22 (2005) 1-24
34. Laird J.M., Souslova V., Wood J.N., and Cervero F. Deficits in visceral pain and referred hyperalgesia in Nav1.8 (SNS/PN3)-null mice. J Neurosci 22 19 (2002) 8352-8356
35. Porreca F., Lai J., Bian D., Wegert S., Ossipov M.H., Eglen R.M., Kassotakis L., Novakovic S., Rabert D.K., Sangameswaran L., and Hunter J.C. A comparison of the potential role of the tetrodotoxin-insensitive sodium channels PN3/SNS and NaN/SNS2, in rat models of chronic pain. Proc Natl Acad Sci USA 96 14 (1999) 7640-7644
36. Lai J., Gold M.S., Kim C.S., Bian D., Ossipov M.H., Hunter J.C., and Porreca F. Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, Nav1.8. Pain 95 1-2 (2002) 143-152
37. Joshi S.K., Mikusa J.P., Hernandez G., Baker S., Shieh C.C., Neelands T., Zhang X.F., Niforatos W., Kage K., Han P., et al. Involvement of the TTX-resistant sodium channel Nav1.8 in inflammatory and neuropathic pain, but not post-operative, pain states. Pain 23 1-2 (2006) 75-82
38. Dong X.-W., Goregoaker S., Engler H., Zhou X., Mark L., Crona J., Terry R., Hunter J., and Priestley T. Small interfering RNA-mediated selective knockdown of Nav1.8 tetrodotoxin-resistant sodium channel reverses mechanical allodynia in neuropathic rats. Neuroscience 146 (2007) 812-821. This is the most recent demonstration using molecular biological approaches of the role Nav1.8 channels play in pain signaling. Using small interfering RNAs the authors demonstrate that knockdown of Nav1.8 leads to reductions in pain when tested in the chronic constriction injury model in rats.
39. Priest B.T., Murphy B.A., Lindia J.A., Diaz C., Abbadie C., Ritter A.M., Liberator P., Iyer L.M., Kash S.F., Kohler M.G., et al. Contribution of the tetrodotoxin-resistant voltage-gated sodium channel Nav1.9 to sensory transmission and nociceptive behavior. Proc Natl Acad Sci USA 102 26 (2005) 9382-9387
40. Amaya F., Wang H., Costigan M., Allchome A.J., Hatcher J.P., Egerton J., Stean T., Morisset V., Grose D., Gunthorpe M.J., et al. The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity. J Neurosci 26 50 (2006) 12852-12860. This report extends studies of Nav1.9 and confirms a key role for this channel in signaling pain following a variety of inflammatory stimuli such as prostaglandin E2 and bradykinin by using Nav1.9 knockout mice. These animals still experience neuropathic pain consistent with earlier studies.
41. Wallace M.J. Update on pharmacotherapy guidelines for treatment of neuropathic pain. Curr Pain Headache Rep 11 3 (2007) 208-214
42. Jarvis M.F., Honore P., Shieh C.C., Chapman M., Joshi S., Zhang X.F., Kort M., Carroll W., Marron B., Atkinson R., et al. A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proc Natl Acad Sci USA 104 20 (2007) 8520-8525. This study is the first to report that very selective (>100-fold) small molecules can be identified that block Nav1.8. The authors go on to show that selective pharmacological block of Nav1.8 is efficacious in a number of pain models.
43. Hoyt S.B., London C., Gorin D., Wyvratt M.J., Fisher M.H., Abbadie C., Felix J.P., Garcia M.L., Li X., Lyons K.A., et al. Discovery of a novel class of benzazepinone Nav1.7 blockers: potential treatments for neuropathic pain. Bioorg Med Chem Lett 17 16 (2007) 4630-4634
44. Liberatore A.-M., Schulz J., Favre-Guilmard C., Pommier J., Lannoy J., Pawlowski E., Barthelemy M.-A., Huchet M., Auguet M., Chabrier P.-E., and Bigg D. Butyl 2-(4[1.1′-biphenyl]-4-ul-1H-imidazol-2-yl)ethylcarbamate, a potent sodium channel blocker for the treatment of neuropathic pain. Bioorg Med Chem Lett 17 6 (2007) 1746-1749
45. Akada Y., Ogawa S., Amano K.-I., Fukudome Y., Yamasaki F., Itoh M., and Yamamoto I. Potent analgesic effects of a putative sodium channel blocker M58373 on formalin-induced and neuropathic pain in rats. Eur J Pharmacol 536 3 (2006) 248-255
46. Brochu R.M., Dick I.E., Tarpley J.W., McGowan E., Gunner D., Herringon J., Shao P.P., Ok D., Li C., Parsons W.H., et al. Block of peripheral nerve sodium channels selectively inhibits features of neuropathic pain in rats. Mol Pharmacol 69 3 (2006) 823-832. There has been debate on whether CNS penetration is necessary for sodium channel blockers to be effective in pain models. These authors are the first to report that a small molecule sodium channel blocker that does not penetrate the CNS is active in pre-clinical models of pain.
47. Shao P.P., Ok D., Fisher M.H., Garcia M.L., Kaczorowski G.J., Li C., Lyons K.A., Martin W.J., Meinke P.T., Priest B.T., et al. Novel cyclopentane dicarboxamide sodium channel blockers as a potential treatment for chronic pain. Bioorg Med Chem Lett 15 7 (2005) 1901-1907
48. Ok D., Li C., Abbbadie C., Felix J.P., Fisher M.H., Garcia M.L., Kaczorowski G.J., Lyons K.A., Martin W.J., Priest B.T., et al. Synthesis and SAR of 1,2-trans-(1-hydroxy-3-phenylprop-1-yl)cyclopentane carboxamide derivatives, a new class of sodium channel blockers. Bioorg Med Chem Lett 16 5 (2006) 1358-1361
49. Ilyin V.I., Pomonis J.D., Whiteside G.T., Harrison J.E., Pearson M.S., Mark L., Turchin P.I., Gottshall S., Carter R.B., Nguyen P., et al. Pharmacology of 2-[4-(4-chloro-2-fluorophenoxy) phenyl] pyrimidine-4-carboxamide: a potent, broad spectrum state-dependent sodium channel blocker for treating pain states. J Pharmacol Exp Ther 318 3 (2006) 1083-1093
50. Shao B., Victory S., Ilyin V.I., Goehring R.R., Sun Q., Hogenkamp D., Hodges D.D., Islam K., Sha D., Zhang C., et al. Phenoxyphenyl pyridines as novel state-dependent, high potency sodium channel inhibitors. J Med Chem 47 17 (2004) 4277-4285
51. + channel blocker, in experimental animal models of inflammatory and neuropathic pain. Pain 102 1-2 (2003) 17-25