title: A genome-wide Drosophila screen for heat nociception identifies α2δ3 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 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.
authors.affiliation: Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria.
authors.forename: G Gregory
authors.initials: GG
authors.lastname: Neely
authors.forename: Andreas
authors.initials: A
authors.lastname: Hess
authors.forename: Michael
authors.initials: M
authors.lastname: Costigan
authors.forename: Alex C
authors.initials: AC
authors.lastname: Keene
authors.forename: Spyros
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authors.lastname: Goulas
authors.forename: Michiel
authors.initials: M
authors.lastname: Langeslag
authors.forename: Robert S
authors.initials: RS
authors.lastname: Griffin
authors.forename: Inna
authors.initials: I
authors.lastname: Belfer
authors.forename: Feng
authors.initials: F
authors.lastname: Dai
authors.forename: Shad B
authors.initials: SB
authors.lastname: Smith
authors.forename: Luda
authors.initials: L
authors.lastname: Diatchenko
authors.forename: Vaijayanti
authors.initials: V
authors.lastname: Gupta
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Xia
authors.forename: Sabina
authors.initials: S
authors.lastname: Amann
authors.forename: Silke
authors.initials: S
authors.lastname: Kreitz
authors.forename: Cornelia
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authors.lastname: Heindl-Erdmann
authors.forename: Susanne
authors.initials: S
authors.lastname: Wolz
authors.forename: Cindy V
authors.initials: CV
authors.lastname: Ly
authors.forename: Suchir
authors.initials: S
authors.lastname: Arora
authors.forename: Rinku
authors.initials: R
authors.lastname: Sarangi
authors.forename: Debasis
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authors.lastname: Dan
authors.forename: Maria
authors.initials: M
authors.lastname: Novatchkova
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenzweig
authors.forename: Dustin G
authors.initials: DG
authors.lastname: Gibson
authors.forename: Darwin
authors.initials: D
authors.lastname: Truong
authors.forename: Daniel
authors.initials: D
authors.lastname: Schramek
authors.forename: Tamara
authors.initials: T
authors.lastname: Zoranovic
authors.forename: Shane J F
authors.initials: SJ
authors.lastname: Cronin
authors.forename: Belinda
authors.initials: B
authors.lastname: Angjeli
authors.forename: Kay
authors.initials: K
authors.lastname: Brune
authors.forename: Georg
authors.initials: G
authors.lastname: Dietzl
authors.forename: William
authors.initials: W
authors.lastname: Maixner
authors.forename: Arabella
authors.initials: A
authors.lastname: Meixner
authors.forename: Winston
authors.initials: W
authors.lastname: Thomas
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Pospisilik
authors.forename: Mattias
authors.initials: M
authors.lastname: Alenius
authors.forename: Michaela
authors.initials: M
authors.lastname: Kress
authors.forename: Sai
authors.initials: S
authors.lastname: Subramaniam
authors.forename: Paul A
authors.initials: PA
authors.lastname: Garrity
authors.forename: Hugo J
authors.initials: HJ
authors.lastname: Bellen
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Woolf
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
mesh_terms: D000328:Adult; D000818:Animals; D001416:Back Pain / Q000235:genetics; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D055106:Genome-Wide Association Study; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D010146:Pain / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D034622:RNA Interference
chemical_list: C531012:CACNA2D3 protein, human; C553974:CACNA2D3 protein, mouse; D015220:Calcium Channels; D029721:Drosophila Proteins; C528236:stj protein, Drosophila