A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha 2 delta 3 as an Evolutionarily Conserved Pain Gene
In: Cell, Jg. 143 (2010), Heft 4, S. 628-638
Online
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Zugriff:
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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A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha 2 delta 3 as an Evolutionarily Conserved Pain Gene
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Autor/in / Beteiligte Person: | Neely, G Gregory ; Hess, Andreas ; Costigan, Michael ; Keene, Alex C ; Goulas, Spyros ; Langeslag, Michiel ; Griffin, Robert S ; Belfer, Inna ; Dai, Feng ; Smith, Shad B ; Diatchenko, Luda ; Gupta, Vaijayanti ; Xia, Cui-Ping ; Amann, Sabina ; Kreitz, Silke ; Heindl-Erdmann, Cornelia ; Wolz, Susanne ; Ly, Cindy V ; Sarangi, Rinku ; Dan, Debasis ; Novatchkova, Maria ; Rosenzweig, Mark ; Gibson, Dustin G ; Truong, Darwin ; Schramek, Daniel ; Zoranovic, Tamara ; Cronin, Shane J F ; Angjeli, Belinda ; Brune, Kay ; Dietzl, Georg ; Maixner, William ; Meixner, Arabella ; Thomas, Winston ; Pospisilik, J Andrew ; Alenius, Mattias ; Kress, Michaela ; Subramaniam, Sai ; Garrity, Paul A ; Bellen, Hugo J ; Woolf, Clifford J ; Penninger, Josef M |
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Zeitschrift: | Cell, Jg. 143 (2010), Heft 4, S. 628-638 |
Veröffentlichung: | 2010 |
Medientyp: | unknown |
ISSN: | 0092-8674 (print) ; 1097-4172 (print) |
DOI: | 10.1016/j.cell.2010.09.047 |
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