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

S. Luvisetto, S. Marinelli, M. S. Panasiti, F. R. D'Amato, C. F. Fletcher, F. Pavone, D. Pietrobon

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)823-832
Number of pages10
JournalNeuroscience
Volume142
Issue number3
DOIs
Publication statusPublished - Oct 27 2006

Keywords

  • formalin
  • inflammatory pain
  • knock-out mice
  • neuropathic pain
  • tail-flick
  • writhing

ASJC Scopus subject areas

  • Neuroscience(all)

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    Luvisetto, S., Marinelli, S., Panasiti, M. S., D'Amato, F. R., Fletcher, C. F., Pavone, F., & Pietrobon, D. (2006). Pain sensitivity in mice lacking the Cav2.1α1 subunit of P/Q-type Ca2+ channels. Neuroscience, 142(3), 823-832. https://doi.org/10.1016/j.neuroscience.2006.06.049