Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway
Drosophila Nociceptive Sensitization Requires BMP Signaling via the Canonical SMAD Pathway
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DOI：
10.1523/jneurosci.3458-16.2017
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发表时间：
2017-08-30
影响因子：
5.3
通讯作者：
Ganter, Geoffrey K.
中科院分区：
文献类型：
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作者：
Follansbee, Taylor L.;Gjelsvik, Kayla J.;Ganter, Geoffrey K.
伤害性敏化是慢性疼痛的一个常见特征，但其基本细胞机制仅被部分了解。本研究使用果蝇模型系统和候选基因方法来鉴定调节损伤诱导的伤害性敏化途径（可能是 Hedgehog 下游）所需的新成分。这项研究表明，RNAi 沉默骨形态发生蛋白 (BMP) 信号通路成员 Decapentaplegic (Dpp)，特别是在 IV 类多树突伤害性神经元中，可显着减弱紫外线损伤引起的敏化。此外，在没有损伤的情况下，IV 类神经元中 Dpp 的过度表达足以诱发热超敏反应。还证明了伤害性敏化中各种 BMP 受体和 SMAD 信号转导途径成员的需要。 BMP 信号传导的影响很大程度上是致敏途径特异的，与无损伤时伤害感受的变化或树突形态的变化无关。因此，结果表明 Dpp 及其途径在伤害性敏化中发挥着至关重要且新颖的作用。由于 BMP 家族在脊椎动物和无脊椎动物之间非常保守，因此本研究中分析的成分似乎代表了治疗人类慢性疼痛的潜在治疗靶点。
Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the Drosophila melanogaster model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans.