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A genome-wide Drosophila screen for heat nociception identifies ?2?3 as an evolutionarily conserved pain gene.

ABSTRACT: 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 ?2? family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (?2?3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, ?2?3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in ?2?3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in ?2?3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.

SUBMITTER: Neely GG 

PROVIDER: S-EPMC3040441 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene.

Neely G Gregory GG   Hess Andreas A   Costigan Michael M   Keene Alex C AC   Goulas Spyros S   Langeslag Michiel M   Griffin Robert S RS   Belfer Inna I   Dai Feng F   Smith Shad B SB   Diatchenko Luda L   Gupta Vaijayanti V   Xia Cui-Ping CP   Amann Sabina S   Kreitz Silke S   Heindl-Erdmann Cornelia C   Wolz Susanne S   Ly Cindy V CV   Arora Suchir S   Sarangi Rinku R   Dan Debasis D   Novatchkova Maria M   Rosenzweig Mark M   Gibson Dustin G DG   Truong Darwin D   Schramek Daniel D   Zoranovic Tamara T   Cronin Shane J F SJ   Angjeli Belinda B   Brune Kay K   Dietzl Georg G   Maixner William W   Meixner Arabella A   Thomas Winston W   Pospisilik J Andrew JA   Alenius Mattias M   Kress Michaela M   Subramaniam Sai S   Garrity Paul A PA   Bellen Hugo J HJ   Woolf Clifford J CJ   Penninger Josef M JM  

Cell 20101101 4

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 α2δ family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (α2δ3) also exhibit impaired behavioral heat pain sensitivity. In addition, in  ...[more]

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