Painful research: Identification of a small-molecule inhibitor that selectively targets Nav1.8 sodium channels

Molecular Interventions

Volumn 7, Issue 4, 2007, Pages 192-195

  Rush, Anthony M ^a   Cummins, Theodore R ^b  

^a NEUROSOLUTIONS LTD   (United Kingdom)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

A 803467; SODIUM CHANNEL BLOCKING AGENT; SODIUM CHANNEL V1.8; UNCLASSIFIED DRUG; VOLTAGE GATED SODIUM CHANNEL;

ACTION POTENTIAL; BINDING SITE; DEPOLARIZATION; DISEASE MODEL; DRUG EFFECT; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG RESEARCH; DRUG STRUCTURE; HUMAN; MOLECULAR SIZE; NONHUMAN; PAIN; REVIEW; SODIUM CURRENT; SPINAL GANGLION;

ANILINE COMPOUNDS; ANIMALS; FURANS; HUMANS; NEURONS; NOCICEPTORS; PAIN; PROTEIN ISOFORMS; SODIUM CHANNEL BLOCKERS; SODIUM CHANNELS;

EID: 34548755733     PISSN: 15340384     EISSN: 15432548     Source Type: Journal    
DOI: 10.1124/mi.7.4.4     Document Type: Review

References (20)

1. v1.8 and has a long-lasting analgesic activity. Biochemistry 45, 7404-7414 (2006).
2. v1.8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits. Proc. Natl. Acad. Sci. U.S.A. 103, 17030-17035 (2006).
3. v1.8, as described in this Viewpoint.
4. Rush, A.M., Cummins, T.R., and Waxman, S.G. Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons. J. Physiol. 579, 1-14 (2007).
5. v1.7 on excitability depends on expression of Nav1.8 channels.
6. Amir, R., Argoff, C.E., Bennett, G.J., Cummins, T.R., Durieux, M.E., Gerner, P., Gold, M.S., Porreca, F., and Strichartz, G.R. The role of sodium channels in chronic inflammatory and neuropathic pain. J. Pain 7, S1-S29 (2006).
7. v1.8.
8. v1.9.
9. + channels. J. Neurophysiol. 86, 241-248 (2001).
10. + current in nociceptors. Proc. Natl. Acad. Sci. U.S.A. 93, 1108-1112 (1996). This was the first demonstration that inflammatory agents could increase the activity of TTX-resistant sodium channels, which would be likely to contribute to nociceptor sensitization.
11. v1.9 sodium current in mouse DRG neurons via G-proteins. Brain Res. 1023, 264-271 (2004).
12. v1.8 has a crucial role in pain mechanisms.
13. v1.8 in NGF-induced hyperalgesia, but not neuropathic pain. Neuroreport 12, 3077-8300 (2001).
14. Amaya, F., Wang, H., Costigan, M.. et al. The voltage-gated sodium channel Na(v)1.9 is an effector of peripheral inflammatory pain hypersensitivity. J. Neurosci. 26,12852-12860 (2006).
15. Fjell, J., Cummins, T.R., Dib-Hajj, S.D., Fried, K., Black, J.A., and Waxman, S.G. Differential role of GDNF and NGF in the maintenance of two TTX- resistant sodium channels in adult DRG neurons. Mol. Brain Res. 67, 267-282 (1999).
16. v1.8 could reduce neuropathic pain.
17. 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 Na(V)1.8 tetrodotoxin-resistant sodium channel reverses mechanical allodynia in neuropathic rats. Neuroscience 146, 812-821 (2007).
18. v1.8 is essential for pain at low temperatures. Nature 447, 855-858 (2007).
19. v1.7 channels seems to cause a complete, and relatively specific, insensitivity to pain in humans.
20. v1.6 is expressed along nonmyelinated axons and it contributes to conduction. Mol. Brain Res. 105, 19-28 (2002).