The role of voltage-gated Ca2+ (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 Cava, 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)2.1 alpha(1) subunit of P/Q-type channels. Homozygous null mutant Ca(v)2.1 alpha(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)2.1 alpha(1)-/- mice showed reduced tall withdrawal latencies in the tail-flick test and reduced abdominal writhes in the acetic acid writhing test. Adult heterozygous Ca(v)2.1 alpha(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. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.

Pain sensitivity in mice lacking the Ca(v)2.1 alpha(1) subunit of P/Q-type Ca2+ channels

PIETROBON, DANIELA
2006

Abstract

The role of voltage-gated Ca2+ (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 Cava, 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)2.1 alpha(1) subunit of P/Q-type channels. Homozygous null mutant Ca(v)2.1 alpha(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)2.1 alpha(1)-/- mice showed reduced tall withdrawal latencies in the tail-flick test and reduced abdominal writhes in the acetic acid writhing test. Adult heterozygous Ca(v)2.1 alpha(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. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/1564470
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