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

Abstract We investigated the antinociceptive action of amlodipine, a dihydropyridine derivative, which acts on both L- and N-type voltage-dependent Ca 2+ 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 α 1A , α 1B , α 1E  , α 1F , α 1H , 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 Ca 2+ 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 Ca 2+ channels in the primary nociceptive afferent fibers. Blocking of the Ca 2+ channels results in attenuation of synaptic transmission of nociceptive neurons. Furthermore, it is suggested that some N-type Ca 2+ channel blockers might have therapeutic potential as analgesics when applied directly into the subarachnoidal space.