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

G. Gregory Neely, Andreas Hess, Michael Costigan, Alex C. Keene, Spyros Goulas, Michiel Langeslag, Robert S. Griffin, Inna Belfer, Feng Dai, Shad B. Smith, Luda Diatchenko, Vaijayanti Gupta, Cui ping Xia, Sabina Amann, Silke Kreitz, Cornelia Heindl-Erdmann, Susanne Wolz, Cindy V. Ly, Suchir Arora, Rinku SarangiDebasis Dan, Maria Novatchkova, Mark Rosenzweig, Dustin G. Gibson, Darwin Truong, Daniel Schramek, Tamara Zoranovic, Shane J.F. Cronin, Belinda Angjeli, Kay Brune, Georg Dietzl, William Maixner, Arabella Meixner, Winston Thomas, J. Andrew Pospisilik, Mattias Alenius, Michaela Kress, Sai Subramaniam, Paul A. Garrity, Hugo J. Bellen, Clifford J. Woolf, Josef M. Penninger

Research output: Contribution to journalArticlepeer-review

175 Scopus citations

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 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 humans, α2δ3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in α2δ3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in α2δ3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.

Original languageEnglish
Pages (from-to)628-638
Number of pages11
JournalCell
Volume143
Issue number4
DOIs
StatePublished - Nov 12 2010

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