• Pain · Aug 2022

    Prdm12 modulates pain-related behavior by remodeling gene expression in mature nociceptors.

    • Aurore Latragna, Alba Sabaté San José, Panagiotis Tsimpos, Simon Vermeiren, Roberta Gualdani, Sampurna Chakrabarti, Gerard Callejo, Simon Desiderio, Orr Shomroni, Maren Sitte, Sadia Kricha, Maëlle Luypaert, Benoit Vanhollebeke, Geoffroy Laumet, Gabriela Salinas, SmithEwan St JohnESJDepartment of Pharmacology, University of Cambridge, Cambridge, United Kingdom., Laurence Ris, and Eric J Bellefroid.
    • ULB Neuroscience Institute (UNI), Université Libre de Bruxelles (ULB), Gosselies, Belgium.
    • Pain. 2022 Aug 1; 163 (8): e927e941e927-e941.

    AbstractPrdm12 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.Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

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