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

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.

Pubmed ID: 21074052

Authors

  • 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 DG
  • Truong D
  • Schramek D
  • Zoranovic T
  • Cronin SJ
  • 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

Journal

Cell

Publication Data

November 12, 2010

Associated Grants

  • Agency: NIGMS NIH HHS, Id: 1 F32GM086207-01
  • Agency: NIGMS NIH HHS, Id: F32 GM086207
  • Agency: NIGMS NIH HHS, Id: F32 GM086207-02
  • Agency: NINDS NIH HHS, Id: NS038253
  • Agency: NINDS NIH HHS, Id: NS039518
  • Agency: NINDS NIH HHS, Id: NS044232
  • Agency: NINDS NIH HHS, Id: P01 NS072040
  • Agency: NINDS NIH HHS, Id: R01 NS038253
  • Agency: NINDS NIH HHS, Id: R01 NS038253-12
  • Agency: NINDS NIH HHS, Id: R01 NS039518
  • Agency: NINDS NIH HHS, Id: R01 NS039518-09
  • Agency: NINDS NIH HHS, Id: R01 NS058870
  • Agency: NINDS NIH HHS, Id: R01 NS058870-04
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

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