Journal
NEUROSCIENCE
Volume 142, Issue 3, Pages 823-832Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2006.06.049
Keywords
tail-flick; writhing; formalin; inflammatory pain; neuropathic pain; knock-out mice
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Funding
- Telethon [E.1297] Funding Source: Medline
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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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