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- Neely, G Gregory, et al.
(författare)
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A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha 2 delta 3 as an Evolutionarily Conserved Pain Gene
- 2010
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Ingår i: Cell. - : Elsevier Science B.V., Amsterdam.. - 0092-8674 .- 1097-4172. ; 143:4, s. 628-638
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Tidskriftsartikel (refereegranskat)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 alpha 2 delta family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (alpha 2 delta 3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, alpha 2 delta 3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in alpha 2 delta 3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in alpha 2 delta 3 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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