A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha2delta3 as an Evolutionarily Conserved Pain Gene

A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha2delta3 as an Evolutionarily Conserved Pain Gene

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

Cell

2010

Biomarkers of Pain

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.

2010

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