Pain sensitivity in mice lacking the Ca(v)2.1alpha1 subunit of P/Q-type Ca2+ channels.
The role of voltage-gated Ca(2+) (Ca(V)) channels in pain mechanisms has been the object of intense investigation using pharmacological approaches and, more recently, using mutant mouse models lacking the Ca(V)alpha(l) pore-forming subunit of N-, R- and T-type channels. The role of P/Q-type channels in nociception and pain transmission has been investigated by pharmacological approaches but remains to be fully elucidated. To address this issue, we have analyzed pain-related behavioral responses of null mutant mice for the Ca(V)2.1alpha(1) subunit of P/Q-type channels. Homozygous null mutant Ca(V)2.1alpha(1)-/- mice developed dystonia at 10-12 days after birth and did not survive past weaning. Tested at ages where motor deficit was either absent or very mild, Ca(V)2.1alpha(1)-/- mice showed reduced tail withdrawal latencies in the tail-flick test and reduced abdominal writhes in the acetic acid writhing test. Adult heterozygous Ca(V)2.1alpha(1)+/- mice did not show motor deficits in the rotarod and activity cage tests and did not show alterations in pain responses in the tail-flick test and the acetic acid writhing test. Strikingly, they showed a reduced licking response during the second phase of formalin-induced inflammatory pain and a reduced mechanical allodynia in the chronic constriction injury model of neuropathic pain. Our findings show that P/Q-type channels play an antinociceptive role in sensitivity to non-injurious noxious thermal stimuli and a pronociceptive role in inflammatory and neuropathic pain states, pointing to an important role of Ca(V)2.1 channels in central sensitization.
Luvisetto
S
S
CNR Institute of Neuroscience, Section of Psychobiology and Psychopharmacology, Via del Fosso di Fiorano 64, 00143 Roma, Italy. siro.luvisetto@ipsifar.rm.cnr.it
Marinelli
S
S
Panasiti
M S
MS
D'Amato
F R
FR
Fletcher
C F
CF
Pavone
F
F
Pietrobon
D
D
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D020864:Calcium Channels, N-Type / Q000172:deficiency*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D010146:Pain / Q000235:genetics*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology*; D021122:Protein Subunits / Q000235:genetics; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time / Q000235:genetics; D013997:Time Factors
D020864:Calcium Channels, N-Type; D021122:Protein Subunits