RRC ID 11674
Author 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.
Title A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene.
Journal Cell
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 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.
Volume 143(4)
Pages 628-38
Published 2010-11-12
DOI 10.1016/j.cell.2010.09.047
PII S0092-8674(10)01133-5
PMID 21074052
PMC PMC3040441
MeSH Adult Animals Back Pain / genetics Calcium Channels / genetics* Calcium Channels / metabolism Drosophila / genetics* Drosophila Proteins / genetics* Drosophila Proteins / metabolism Gene Knockdown Techniques Genome-Wide Association Study Hot Temperature Humans Mice Pain / genetics* Polymorphism, Single Nucleotide RNA Interference
IF 31.398
Times Cited 102
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Drosophila NP1574-Gal4 (DGRC#104034 or DGRC#112708)