Pain sensitivity in mice lacking the Cav2.1α1 subunit of P/Q-type Ca2+ channels

The role of voltage-gated Ca2+ (CaV) channels in pain mechanisms has been the object of intense investigation using pharmacological approaches and, more recently, using mutant mouse models lacking the CaVαl 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 CaV2.1α1 subunit of P/Q-type channels. Homozygous null mutant CaV2.1α1−/− 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, CaV2.1α1−/− mice showed reduced tail withdrawal latencies in the tail-flick test and reduced abdominal writhes in the acetic acid writhing test. Adult heterozygous CaV2.1α1+/− 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 CaV2.1 channels in central sensitization.