A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha 2 delta 3 as an Evolutionarily Conserved Pain Gene
2010 (English)In: CELL, ISSN 0092-8674, Vol. 143, no 4, 628-638 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam. , 2010. Vol. 143, no 4, 628-638 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-62750DOI: 10.1016/j.cell.2010.09.047ISI: 000284149100019OAI: oai:DiVA.org:liu-62750DiVA: diva2:374205