The Role of Sodium Channels in Chronic Inflammatory and Neuropathic Pain

Ron Amir, Charles E. Argoff, Gary J. Bennett, Theodore R. Cummins, Marcel E. Durieux, Peter Gerner, Michael S. Gold, Frank Porreca, Gary R. Strichartz

Research output: Contribution to journalArticle

255 Citations (Scopus)

Abstract

Clinical and experimental data indicate that changes in the expression of voltage-gated sodium channels play a key role in the pathogenesis of neuropathic pain and that drugs that block these channels are potentially therapeutic. Clinical and experimental data also suggest that changes in voltage-gated sodium channels may play a role in inflammatory pain, and here too sodium-channel blockers may have therapeutic potential. The sodium-channel blockers of interest include local anesthetics, used at doses far below those that block nerve impulse propagation, and tricyclic antidepressants, whose analgesic effects may at least partly be due to blockade of sodium channels. Recent data show that local anesthetics may have pain-relieving actions via targets other than sodium channels, including neuronal G protein-coupled receptors and binding sites on immune cells. Some of these actions occur with nanomolar drug concentrations, and some are detected only with relatively long-term drug exposure. There are 9 isoforms of the voltage-gated sodium channel α-subunit, and several of the isoforms that are implicated in neuropathic and inflammatory pain states are expressed by somatosensory primary afferent neurons but not by skeletal or cardiovascular muscle. This restricted expression raises the possibility that isoform-specific drugs might be analgesic and lacking the cardiotoxicity and neurotoxicity that limit the use of current sodium-channel blockers. Perspective: Changes in the expression of neuronal voltage-gated sodium channels may play a key role in the pathogenesis of both chronic neuropathic and chronic inflammatory pain conditions. Drugs that block these channels may have therapeutic efficacy with doses that are far below those that impair nerve impulse propagation or cardiovascular function.

Original languageEnglish (US)
JournalJournal of Pain
Volume7
Issue number5 SUPPL.
DOIs
StatePublished - May 2006

Fingerprint

Sodium Channels
Voltage-Gated Sodium Channels
Neuralgia
Chronic Pain
Sodium Channel Blockers
Protein Isoforms
Pharmaceutical Preparations
Local Anesthetics
Action Potentials
Analgesics
Afferent Neurons
Pain
Tricyclic Antidepressive Agents
G-Protein-Coupled Receptors
Therapeutics
Binding Sites
Muscles

Keywords

  • Allodynia
  • hyperalgesia
  • inflammatory pain
  • local anesthetics
  • neuropathic pain
  • sodium channels

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Clinical Neurology
  • Neurology
  • Nursing(all)

Cite this

Amir, R., Argoff, C. E., Bennett, G. J., Cummins, T. R., Durieux, M. E., Gerner, P., ... Strichartz, G. R. (2006). The Role of Sodium Channels in Chronic Inflammatory and Neuropathic Pain. Journal of Pain, 7(5 SUPPL.). https://doi.org/10.1016/j.jpain.2006.01.444

The Role of Sodium Channels in Chronic Inflammatory and Neuropathic Pain. / Amir, Ron; Argoff, Charles E.; Bennett, Gary J.; Cummins, Theodore R.; Durieux, Marcel E.; Gerner, Peter; Gold, Michael S.; Porreca, Frank; Strichartz, Gary R.

In: Journal of Pain, Vol. 7, No. 5 SUPPL., 05.2006.

Research output: Contribution to journalArticle

Amir, R, Argoff, CE, Bennett, GJ, Cummins, TR, Durieux, ME, Gerner, P, Gold, MS, Porreca, F & Strichartz, GR 2006, 'The Role of Sodium Channels in Chronic Inflammatory and Neuropathic Pain', Journal of Pain, vol. 7, no. 5 SUPPL.. https://doi.org/10.1016/j.jpain.2006.01.444
Amir R, Argoff CE, Bennett GJ, Cummins TR, Durieux ME, Gerner P et al. The Role of Sodium Channels in Chronic Inflammatory and Neuropathic Pain. Journal of Pain. 2006 May;7(5 SUPPL.). https://doi.org/10.1016/j.jpain.2006.01.444
Amir, Ron ; Argoff, Charles E. ; Bennett, Gary J. ; Cummins, Theodore R. ; Durieux, Marcel E. ; Gerner, Peter ; Gold, Michael S. ; Porreca, Frank ; Strichartz, Gary R. / The Role of Sodium Channels in Chronic Inflammatory and Neuropathic Pain. In: Journal of Pain. 2006 ; Vol. 7, No. 5 SUPPL.
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