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pubmed: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 ?2? family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (?2?3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, ?2?3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in ?2?3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in ?2?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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