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Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons.

Publication ,  Journal Article
Liu, L; Oortgiesen, M; Li, L; Simon, SA
Published in: J Neurophysiol
February 2001

Capsaicin, the pungent ingredient in hot pepper, activates nociceptors to produce pain and inflammation. However, repeated exposures of capsaicin will cause desensitization to nociceptive stimuli. In cultured trigeminal ganglion (TG) neurons, we investigated mechanisms underlying capsaicin-mediated inhibition of action potentials (APs) and modulation of voltage-gated sodium channels (VGSCs). Capsaicin (1 microM) inhibited APs and VGSCs only in capsaicin-sensitive neurons. Repeated applications of capsaicin produced depolarizing potentials but failed to evoke APs. The capsaicin-induced inhibition of VGSCs was prevented by preexposing the capsaicin receptor antagonist, capsazepine (CPZ). The magnitude of the capsaicin-induced inhibition of VGSCs was dose dependent, having a K(1/2) = 0.45 microM. The magnitude of the inhibition of VGSCs was proportional to the capsaicin induced current (for -I(CAP) < 0.2 nA). Capsaicin inhibited activation of VGSCs without changing the voltage dependence of activation or markedly changing channel inactivation and use-dependent block. To explore the changes leading to this inhibition, it was found that capsaicin increased cAMP with a K(1/2) = 0.18 microM. At 1 microM capsaicin, this cAMP generation was inhibited 64% by10 microM CPZ, suggesting that activation of capsaicin receptors increased cAMP. The addition of 100 microM CPT-cAMP increased the capsaicin-activated currents but inhibited the VGSCs in both capsaicin-sensitive and -insensitive neurons. In summary, the inhibitory effects of capsaicin on VGSCs and the generation of APs are mediated by activation of capsaicin receptors. The capsaicin-induced activation of second messengers, such as cAMP, play a part in this modulation. These data distinguish two pathways by which neuronal sensitivity can be diminished by capsaicin: by modulation of the capsaicin receptor sensitivity, since the block of VGSCs is proportional to the magnitude of the capsaicin-evoked currents, and by modulation of VGSCs through second messengers elevated by capsaicin receptor activation. These mechanisms are likely to be important in understanding the analgesic effects of capsaicin.

Duke Scholars

Published In

J Neurophysiol

DOI

ISSN

0022-3077

Publication Date

February 2001

Volume

85

Issue

2

Start / End Page

745 / 758

Location

United States

Related Subject Headings

  • Trigeminal Ganglion
  • Sodium Channels
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Neurology & Neurosurgery
  • Ion Channel Gating
  • Electrophysiology
  • Cells, Cultured
  • Capsaicin
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, L., Oortgiesen, M., Li, L., & Simon, S. A. (2001). Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons. J Neurophysiol, 85(2), 745–758. https://doi.org/10.1152/jn.2001.85.2.745
Liu, L., M. Oortgiesen, L. Li, and S. A. Simon. “Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons.J Neurophysiol 85, no. 2 (February 2001): 745–58. https://doi.org/10.1152/jn.2001.85.2.745.
Liu L, Oortgiesen M, Li L, Simon SA. Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons. J Neurophysiol. 2001 Feb;85(2):745–58.
Liu, L., et al. “Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons.J Neurophysiol, vol. 85, no. 2, Feb. 2001, pp. 745–58. Pubmed, doi:10.1152/jn.2001.85.2.745.
Liu L, Oortgiesen M, Li L, Simon SA. Capsaicin inhibits activation of voltage-gated sodium currents in capsaicin-sensitive trigeminal ganglion neurons. J Neurophysiol. 2001 Feb;85(2):745–758.

Published In

J Neurophysiol

DOI

ISSN

0022-3077

Publication Date

February 2001

Volume

85

Issue

2

Start / End Page

745 / 758

Location

United States

Related Subject Headings

  • Trigeminal Ganglion
  • Sodium Channels
  • Rats, Sprague-Dawley
  • Rats
  • Neurons
  • Neurology & Neurosurgery
  • Ion Channel Gating
  • Electrophysiology
  • Cells, Cultured
  • Capsaicin