Prdm12 is a conserved epigenetic transcriptional regulator that displays restricted expression in nociceptors of the developing peripheral nervous system. In mice, Prdm12 is required for the development of the entire nociceptive lineage. In humans, PRDM12 mutations cause congenital insensitivity to pain, likely because of the loss of nociceptors. Prdm12 expression is maintained in mature nociceptors suggesting a yet-to-be explored functional role in adults. Using Prdm12 inducible conditional knockout mouse models, we report that in adult nociceptors Prdm12 is no longer required for cell survival but continues to play a role in the transcriptional control of a network of genes, many of them encoding ion channels and receptors. We found that disruption of Prdm12 alters the excitability of dorsal root ganglion neurons in culture. Phenotypically, we observed that mice lacking Prdm12 exhibit normal responses to thermal and mechanical nociceptive stimuli but a reduced response to capsaicin and hypersensitivity to formalin-induced inflammatory pain. Together, our data indicate that Prdm12 regulates pain-related behavior in a complex way by modulating gene expression in adult nociceptors and controlling their excitability. The results encourage further studies to assess the potential of Prdm12 as a target for analgesic development.

Prdm12 是一种保守的表观遗传转录调节因子，在发育中的周围神经系统的伤害感受器中表达受限。在小鼠中，Prdm12 是整个伤害感受谱系发育所必需的。在人类中，PRDM12突变会导致先天性对疼痛不敏感，可能是因为伤害感受器的丧失。Prdm12 的表达在成熟的伤害感受器中得以维持，表明其在成人中的功能作用尚待探索。使用Prdm12诱导条件敲除小鼠模型，我们报告说，在成年伤害感受器中，Prdm12 不再是细胞生存所必需的，而是继续在基因网络的转录控制中发挥作用，其中许多基因编码离子通道和受体。我们发现 Prdm12 的破坏会改变培养物中背根神经节神经元的兴奋性。在表型上，我们观察到缺乏Prdm12 的小鼠对热和机械伤害性刺激表现出正常反应，但对辣椒素的反应减弱，并对福尔马林引起的炎性疼痛过敏。总之，我们的数据表明 Prdm12 通过调节成人伤害感受器的基因表达并控制其兴奋性，以复杂的方式调节疼痛相关行为。这些结果鼓励进一步研究评估 Prdm12 作为镇痛开发靶点的潜力。