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 Sarangi & 22 others Debasis Dan, Maria Novatchkova, Mark Rosenzweig, Dustin 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 journalArticle

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

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Nociception
Drosophila
Hot Temperature
Genes
Genome
Pain
Chronic Pain
Instinct
Pain Clinics
Smell
Touch
Acute Pain
Audition
Calcium Channels
Back Pain
RNA Interference
Thalamus
Hearing
Single Nucleotide Polymorphism
Brain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Neely, G. G., Hess, A., Costigan, M., Keene, A. C., Goulas, S., Langeslag, M., ... Penninger, J. M. (2010). A Genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene. Cell, 143(4), 628-638. https://doi.org/10.1016/j.cell.2010.09.047

A Genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene. / 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.; Arora, Suchir; Sarangi, Rinku; Dan, Debasis; Novatchkova, Maria; Rosenzweig, Mark; Gibson, Dustin; 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.

In: Cell, Vol. 143, No. 4, 12.11.2010, p. 628-638.

Research output: Contribution to journalArticle

Neely, GG, Hess, A, Costigan, M, Keene, AC, Goulas, S, Langeslag, M, Griffin, RS, Belfer, I, Dai, F, Smith, SB, Diatchenko, L, Gupta, V, Xia, CP, Amann, S, Kreitz, S, Heindl-Erdmann, C, Wolz, S, Ly, CV, Arora, S, Sarangi, R, Dan, D, Novatchkova, M, Rosenzweig, M, Gibson, D, Truong, D, Schramek, D, Zoranovic, T, Cronin, SJF, Angjeli, B, Brune, K, Dietzl, G, Maixner, W, Meixner, A, Thomas, W, Pospisilik, JA, Alenius, M, Kress, M, Subramaniam, S, Garrity, PA, Bellen, HJ, Woolf, CJ & Penninger, JM 2010, 'A Genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene', Cell, vol. 143, no. 4, pp. 628-638. https://doi.org/10.1016/j.cell.2010.09.047
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. ; Arora, Suchir ; Sarangi, Rinku ; Dan, Debasis ; Novatchkova, Maria ; Rosenzweig, Mark ; Gibson, Dustin ; 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. / A Genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene. In: Cell. 2010 ; Vol. 143, No. 4. pp. 628-638.
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AU - Hess, Andreas

AU - Costigan, Michael

AU - Keene, Alex C.

AU - Goulas, Spyros

AU - Langeslag, Michiel

AU - Griffin, Robert S.

AU - Belfer, Inna

AU - Dai, Feng

AU - Smith, Shad B.

AU - Diatchenko, Luda

AU - Gupta, Vaijayanti

AU - Xia, Cui ping

AU - Amann, Sabina

AU - Kreitz, Silke

AU - Heindl-Erdmann, Cornelia

AU - Wolz, Susanne

AU - Ly, Cindy V.

AU - Arora, Suchir

AU - Sarangi, Rinku

AU - Dan, Debasis

AU - Novatchkova, Maria

AU - Rosenzweig, Mark

AU - Gibson, Dustin

AU - Truong, Darwin

AU - Schramek, Daniel

AU - Zoranovic, Tamara

AU - Cronin, Shane J F

AU - Angjeli, Belinda

AU - Brune, Kay

AU - Dietzl, Georg

AU - Maixner, William

AU - Meixner, Arabella

AU - Thomas, Winston

AU - Pospisilik, J. Andrew

AU - Alenius, Mattias

AU - Kress, Michaela

AU - Subramaniam, Sai

AU - Garrity, Paul A.

AU - Bellen, Hugo J.

AU - Woolf, Clifford J.

AU - Penninger, Josef M.

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