Differential nociceptive responses in mice lacking the alpha(1B) subunit of N-type Ca(2+) channels.
The role of N-type Ca(2+) channels in nociceptive transmission was examined in genetically engineered mice lacking the alpha(1B) subunit of N-type channels and in their heterozygote and wild-type littermates. In alpha(1B)-deficient mice, N-type channel activities in dorsal root ganglion neurons and spinal synaptoneurosomes were eliminated without compensation by other types of voltage-dependent Ca(2+) channels. The alpha(1B)-deficient mice showed a diminution in the phase 2 nociceptive responses more extensively than in the phase 1 nociceptive responses of the formalin test. The alpha(1B)-deficient mice exhibited significantly increased thermal nociceptive thresholds in the hot plate test, but failed to increase mechanical nociceptive thresholds in the tail pinch test. These results suggest a crucial role of N-type channels in nociceptive transmission, especially for persistent pain like phase 2 of the formalin test and for nociception induced by thermal stimuli.
Hatakeyama
S
S
Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Wakamori
M
M
Ino
M
M
Miyamoto
N
N
Takahashi
E
E
Yoshinaga
T
T
Sawada
K
K
Imoto
K
K
Tanaka
I
I
Yoshizawa
T
T
Nishizawa
Y
Y
Mori
Y
Y
Niidome
T
T
Shoji
S
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000235:genetics*; D005727:Ganglia, Spinal / Q000502:physiology*; D006358:Hot Temperature; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009553:Nimodipine / Q000494:pharmacology; D009619:Nociceptors / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D020867:omega-Agatoxin IVA; D009553:Nimodipine; D020866:omega-Conotoxin GVIA