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A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha 2 delta 3 as an Evolutionarily Conserved Pain Gene

Neely, G Gregory (author)
Austrian Academy of Science
Hess, Andreas (author)
University of Erlangen Nurnberg
Costigan, Michael (author)
Harvard University
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Keene, Alex C (author)
NYU
Goulas, Spyros (author)
Austrian Academy of Science
Langeslag, Michiel (author)
Innsbruck Medical University
Griffin, Robert S (author)
Massachusetts General Hospital,Strand Life Science Pvt Ltd
Belfer, Inna (author)
University of Pittsburgh
Dai, Feng (author)
University of Pittsburgh
Smith, Shad B (author)
University N Carolina
Diatchenko, Luda (author)
University N Carolina
Gupta, Vaijayanti (author)
Strand Life Science Pvt Ltd
Xia, Cui-Ping (author)
Austrian Academy Science
Amann, Sabina (author)
Austrian Academy of Science
Kreitz, Silke (author)
University of Erlangen Nurnberg
Heindl-Erdmann, Cornelia (author)
University of Erlangen Nurnberg
Wolz, Susanne (author)
University of Erlangen Nurnberg
Ly, Cindy V (author)
Strand Life Science Pvt Ltd
Sarangi, Rinku (author)
Strand Life Science Pvt Ltd
Dan, Debasis (author)
Strand Life Science Pvt Ltd
Novatchkova, Maria (author)
Austrian Academy of Science
Rosenzweig, Mark (author)
Brandeis University
Gibson, Dustin G (author)
University N Carolina
Truong, Darwin (author)
Austrian Academy of Science
Schramek, Daniel (author)
Austrian Academy of Science
Zoranovic, Tamara (author)
Austrian Academy of Science
Cronin, Shane J F (author)
Austrian Academy of Science
Angjeli, Belinda (author)
Austrian Academy of Science
Brune, Kay (author)
University of Erlangen Nurnberg
Dietzl, Georg (author)
Stanford University
Maixner, William (author)
University N Carolina
Meixner, Arabella (author)
Austrian Academy of Science
Thomas, Winston (author)
Deltagen Inc
Pospisilik, J Andrew (author)
Max Planck Institute
Alenius, Mattias (author)
Linköpings universitet,Hälsouniversitetet,Utvecklingsbiologi
Kress, Michaela (author)
Innsbruck Medical University
Subramaniam, Sai (author)
Strand Life Science Pvt Ltd
Garrity, Paul A (author)
Brandeis University
Bellen, Hugo J (author)
Baylor College of Medicine
Woolf, Clifford J (author)
Harvard University
Penninger, Josef M (author)
Austrian Academy of Science
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 (creator_code:org_t)
Elsevier Science B.V., Amsterdam. 2010
2010
English.
In: Cell. - : Elsevier Science B.V., Amsterdam.. - 0092-8674 .- 1097-4172. ; 143:4, s. 628-638
Related links:
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the alpha 2 delta family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (alpha 2 delta 3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, alpha 2 delta 3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in alpha 2 delta 3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in alpha 2 delta 3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.

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