Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Dr. Bohr Gasse 3-5, A-1030 Vienna, Austria.
Cell. 2010 Nov 12;143(4):628-38. doi: 10.1016/j.cell.2010.09.047.
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.
在全球范围内，急性和慢性疼痛影响了 20%的成年人口，给他们带来了巨大的经济和情感负担。通过在果蝇中进行全基因组神经元特异性 RNAi 敲低，我们报告了一项针对先天行为的全基因组筛选，并鉴定了数百个与热伤害感受相关的基因，包括α2δ 家族钙通道亚基直筒夹克（stj）。stj 同源物 CACNA2D3（α2δ3）突变的小鼠也表现出行为性热痛觉敏感性受损。此外，在人类中，α2δ3 SNP 变体与对急性有害热和慢性背痛的敏感性降低有关。在 α2δ3 突变小鼠中的功能成像显示，从丘脑到高级疼痛中心的热痛觉诱发信号的传递受损。有趣的是，在 α2δ3 突变小鼠中，热痛觉和触觉刺激强烈地交叉激活了涉及视觉、嗅觉和听觉的大脑区域，即联觉。
