Identification of FAM173B as a protein methyltransferase promoting chronic pain Willemen, Hanneke L.D.M. González-Cano, Rafael The authors thank Cilia de Heus for excellent technical support and Rene Scriwanek for the preparation of the electron micrographs for publication (UMCU, Utrecht, the Netherlands). We thank Angela Ho (University of Oslo, Oslo, Norway) for technical assistance. Author Contributions Conceptualization: Hanneke L. D. M. Willemen, Niels Eijkelkamp Chronic pain is a debilitating problem, and insights in the neurobiology of chronic pain are needed for the development of novel pain therapies. A genome-wide association study implicated the 5p15.2 region in chronic widespread pain. This region includes the coding region for FAM173B, a functionally uncharacterized protein. We demonstrate here that FAM173B is a mitochondrial lysine methyltransferase that promotes chronic pain. Knockdown and sensory neuron overexpression strategies showed that FAM173B is involved in persistent inflammatory and neuropathic pain via a pathway dependent on its methyltransferase activity. FAM173B methyltransferase activity in sensory neurons hyperpolarized mitochondria and promoted macrophage/microglia activation through a reactive oxygen species±dependent pathway. In summary, we uncover a role for methyltransferase activity of FAM173B in the neurobiology of pain. These results also highlight FAM173B methyltransferase activity as a potential therapeutic target to treat debilitating chronic pain conditions. 2018-05-10T14:56:37Z 2018-05-10T14:56:37Z 2018-02-14 info:eu-repo/semantics/article Willemen HLDM, Kavelaars A, Prado J, Maas M, Versteeg S, Nellissen LJJ, et al. (2018) Identification of FAM173B as a protein methyltransferase promoting chronic pain. PLoS Biol 16(2): e2003452 [http://hdl.handle.net/10481/50821] http://hdl.handle.net/10481/50821 https://doi.org/10.1371/ journal.pbio.2003452 eng http://creativecommons.org/licenses/by-nc-nd/3.0/es/ info:eu-repo/semantics/openAccess Atribución-NoComercial-SinDerivadas 3.0 España Public Library of Science (PLOS)