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

Cell | 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.

Pubmed ID: 21074052 RIS Download

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Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS039518-09
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS039518
  • Agency: NINDS NIH HHS, United States
    Id: R37 NS039518
  • Agency: NINDS NIH HHS, United States
    Id: P01 NS044232
  • Agency: NIGMS NIH HHS, United States
    Id: F32 GM086207-02
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS038253
  • Agency: NIGMS NIH HHS, United States
    Id: F32 GM086207
  • Agency: NINDS NIH HHS, United States
    Id: P01 NS072040
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS058870-04
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS058870
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS038253-12

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Entrez Gene (tool)

RRID:SCR_002473

Database for genomes that have been completely sequenced, have active research community to contribute gene-specific information, or that are scheduled for intense sequence analysis. Includes nomenclature, map location, gene products and their attributes, markers, phenotypes, and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases. All entries follow NCBI's format for data collections. Content of Entrez Gene represents result of curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases, and from many other databases available from NCBI. Records are assigned unique, stable and tracked integers as identifiers. Content is updated as new information becomes available.

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PANTHER (tool)

RRID:SCR_004869

System that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.

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GOstat (tool)

RRID:SCR_008535

GOstat is a tool that allows you to find statistically overrepresented Gene Ontologies within a group of genes. The Gene-Ontology database (GO: http://www.geneontology.org) provides a useful tool to annotate and analyze the function of large numbers of genes. Modern experimental techniques, as e.g. DNA microarrays, often result in long lists of genes. To learn about the biology in this kind of data it is desirable to find functional annotation or Gene-Ontology groups which are highly represented in the data. This program (GOstat) should help in the analysis of such lists and will provide statistics about the GO terms contained in the data and sort the GO annotations giving the most representative GO terms first. Run GOstat: * Go to search form - Computes GO statistics of a list of genes selected from a microarray. * GOstat Display - You can store results from a previously run and view them here, either by uploading them as a file or putting them on a selected URL. * Upload Custom GO Annotations - This allows you to upload your own GO annotation database and use it with GOstat. Variants of GOstat: * Rank GOstat - Takes input from all genes on microarray instead of using a fixed cutoff and uses ranks using a Wilcoxon test or either ranks or pvalues to score GOs using Kolmogorov-Smirnov statistics. * Gene Abundance GOstats - Takes input from all genes on microarray and sums up the gene abundances for each GO to compute statistics. * Two list GOstat - Compares GO statistics in two independent lists of genes, not necessarily one of them being the complete list the other list is sampled from. Platform: Online tool

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