Redistribution of Nav1.8 in uninjured axons enables neuropathic pain

Michael S. Gold, Daniel Weinreich, Chang Sook Kim, Ruizhong Wang, James Treanor, Frank Porreca, Josephine Lai

Research output: Contribution to journalArticle

313 Citations (Scopus)

Abstract

The underlying mechanisms of neuropathic pain are poorly understood, and existing treatments are mostly ineffective. We recently demonstrated that antisense mediated "knock-down" of the sodium channel isoform, Nav1.8, reverses neuropathic pain behavior after L5/L6 spinal nerve ligation (SNL), implicating a critical functional role of Nav1.8 in the neuropathic state. Here we have investigated mechanisms through which Nav1.8 contributes to the expression of experimental neuropathic pain. Nav1.8 does not appear to contribute to neuropathic pain through an action in injured afferents because the channel is functionally downregulated in the cell bodies of injured neurons and does not redistribute to injured terminals. Although there was little change in Nav1.8 protein or functional channels in the cell bodies of uninjured neurons in L4 ganglia, there was a striking increase in Nav1.8 immunoreactivity along the sciatic nerve. The distribution of Nav1.8 reflected predominantly the presence of functional channels in unmyelinated axons. The C-fiber component of the sciatic nerve compound action potential (CAP) was resistant (>40%) to 100 μM TTX after SNL, whereas both A- and C-fiber components of sciatic nerve CAP were blocked (>90%) by 100 μM TTX in sham-operated rats or the contralateral sciatic nerve of SNL rats. Attenuating expression of Nav1.8 with antisense oligodeoxynucleotides prevented the redistribution of Nav1.8 in the sciatic nerve and reversed neuropathic pain. 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 Nav1.8 would be an effective treatment of neuropathic pain.

Original languageEnglish (US)
Pages (from-to)158-166
Number of pages9
JournalJournal of Neuroscience
Volume23
Issue number1
StatePublished - Jan 1 2003

Fingerprint

Neuralgia
Sciatic Nerve
Axons
Spinal Nerves
Unmyelinated Nerve Fibers
Ligation
Action Potentials
Neurons
Sodium Channels
Oligodeoxyribonucleotides
Ganglia
Protein Isoforms
Down-Regulation
Pain
Wounds and Injuries
Therapeutics
Proteins

Keywords

  • Dorsal root ganglion
  • Nerve injury
  • Nociceptor
  • Peripheral nerve
  • Tetrodotoxin resistant
  • Voltage-gated Na

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Gold, M. S., Weinreich, D., Kim, C. S., Wang, R., Treanor, J., Porreca, F., & Lai, J. (2003). Redistribution of Nav1.8 in uninjured axons enables neuropathic pain. Journal of Neuroscience, 23(1), 158-166.

Redistribution of Nav1.8 in uninjured axons enables neuropathic pain. / Gold, Michael S.; Weinreich, Daniel; Kim, Chang Sook; Wang, Ruizhong; Treanor, James; Porreca, Frank; Lai, Josephine.

In: Journal of Neuroscience, Vol. 23, No. 1, 01.01.2003, p. 158-166.

Research output: Contribution to journalArticle

Gold, MS, Weinreich, D, Kim, CS, Wang, R, Treanor, J, Porreca, F & Lai, J 2003, 'Redistribution of Nav1.8 in uninjured axons enables neuropathic pain', Journal of Neuroscience, vol. 23, no. 1, pp. 158-166.
Gold MS, Weinreich D, Kim CS, Wang R, Treanor J, Porreca F et al. Redistribution of Nav1.8 in uninjured axons enables neuropathic pain. Journal of Neuroscience. 2003 Jan 1;23(1):158-166.
Gold, Michael S. ; Weinreich, Daniel ; Kim, Chang Sook ; Wang, Ruizhong ; Treanor, James ; Porreca, Frank ; Lai, Josephine. / Redistribution of Nav1.8 in uninjured axons enables neuropathic pain. In: Journal of Neuroscience. 2003 ; Vol. 23, No. 1. pp. 158-166.
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