Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice

Manabu Murakami, Osamu Nakagawasai, Shigeo Fujii, Kimiko Kameyama, Shinobu Murakami, Soichi Hozumi, Akihisa Esashi, Ryoo Taniguchi, Teruyuki Yanagisawa, Koichi Tan-no, Takeshi Tadano, Kenji Kitamura, Kensuke Kisara

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23 Citations (Scopus)

Abstract

We investigated the antinociceptive action of amlodipine, a dihydropyridine derivative, which acts on both L- and N-type voltage-dependent Ca2+ channels (VDCCs), in mice. Intrathecal injection of amlodipine (300 nmol/kg) significantly shortened the licking time in the late phase of a formalin test, while no effect was found with another dihydropyridine derivative, nicardipine (300 nmol/kg). Cilnidipine and ω-conotoxin GVIA also showed marked analgesic effects under the same experimental conditions. Transcripts of α1A, α1B, α1E, α1F, α1H, β3, and β4 subunits were detected by polymerase-chain reaction (PCR) in the dorsal root ganglion, suggesting the existence of a variety of voltage-dependent Ca2+ channels. Electrophysiological experiments showed that amlodipine and cilnidipine inhibit N-type currents in the dorsal root ganglion cells. These results suggest that amlodipine, cilnidipine, and ω-conotoxin GVIA exert their antinociceptive actions by blocking N-type Ca2+ channels in the primary nociceptive afferent fibers. Blocking of the Ca2+ channels results in attenuation of synaptic transmission of nociceptive neurons. Furthermore, it is suggested that some N-type Ca2+ channel blockers might have therapeutic potential as analgesics when applied directly into the subarachnoidal space.

Original languageEnglish
Pages (from-to)175-181
Number of pages7
JournalEuropean Journal of Pharmacology
Volume419
Issue number2-3
DOIs
Publication statusPublished - 2001 May 11

Keywords

  • Amlodipine
  • Ca channel
  • Nociception

ASJC Scopus subject areas

  • Pharmacology

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    Murakami, M., Nakagawasai, O., Fujii, S., Kameyama, K., Murakami, S., Hozumi, S., Esashi, A., Taniguchi, R., Yanagisawa, T., Tan-no, K., Tadano, T., Kitamura, K., & Kisara, K. (2001). Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. European Journal of Pharmacology, 419(2-3), 175-181. https://doi.org/10.1016/S0014-2999(01)00985-2