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

First Author  Neely GG Year  2010
Journal  Cell Volume  143
Issue  4 Pages  628-38
PubMed ID  21074052 Mgi Jnum  J:167904
Mgi Id  MGI:4881348 Doi  10.1016/j.cell.2010.09.047
Citation  Neely GG, et al. (2010) A genome-wide Drosophila screen for heat nociception identifies alpha2delta3 as an evolutionarily conserved pain gene. Cell 143(4):628-38
abstractText  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 alpha2delta family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (alpha2delta3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, alpha2delta3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in alpha2delta3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in alpha2delta3 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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