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

Publication ,  Journal Article
Neely, GG; Hess, A; Costigan, M; Keene, AC; Goulas, S; Langeslag, M; Griffin, RS; Belfer, I; Dai, F; Smith, SB; Diatchenko, L; Gupta, V ...
Published in: Cell
November 12, 2010

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.

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

November 12, 2010

Volume

143

Issue

4

Start / End Page

628 / 638

Location

United States

Related Subject Headings

  • RNA Interference
  • Polymorphism, Single Nucleotide
  • Pain
  • Mice
  • Humans
  • Hot Temperature
  • Genome-Wide Association Study
  • Gene Knockdown Techniques
  • Drosophila Proteins
  • Drosophila
 

Citation

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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
Neely, G Gregory, Andreas Hess, Michael Costigan, Alex C. Keene, Spyros Goulas, Michiel Langeslag, Robert S. Griffin, et al. “A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene.Cell 143, no. 4 (November 12, 2010): 628–38. https://doi.org/10.1016/j.cell.2010.09.047.
Neely GG, Hess A, Costigan M, Keene AC, Goulas S, Langeslag M, et al. A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene. Cell. 2010 Nov 12;143(4):628–38.
Neely, G. Gregory, et al. “A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene.Cell, vol. 143, no. 4, Nov. 2010, pp. 628–38. Pubmed, doi:10.1016/j.cell.2010.09.047.
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 C-P, Amann S, Kreitz S, Heindl-Erdmann C, Wolz S, Ly CV, Arora S, Sarangi R, Dan D, Novatchkova M, Rosenzweig M, Gibson DG, 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. A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene. Cell. 2010 Nov 12;143(4):628–638.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

November 12, 2010

Volume

143

Issue

4

Start / End Page

628 / 638

Location

United States

Related Subject Headings

  • RNA Interference
  • Polymorphism, Single Nucleotide
  • Pain
  • Mice
  • Humans
  • Hot Temperature
  • Genome-Wide Association Study
  • Gene Knockdown Techniques
  • Drosophila Proteins
  • Drosophila