Identification of FAM173B as a protein methyltransferase promoting chronic pain.

• Main Authors: Hanneke L D M Willemen, Annemieke Kavelaars, Judith Prado, Mirjam Maas, Sabine Versteeg, Lara J J Nellissen, Jeshua Tromp, Rafael Gonzalez Cano, Wenjun Zhou, Magnus E Jakobsson, Jędrzej Małecki, George Posthuma, Abdella M Habib, Cobi J Heijnen, Pål Ø Falnes, Niels Eijkelkamp
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2018-02-01
• Series: PLoS Biology
• Online Access: http://europepmc.org/articles/PMC5828452?pdf=render
• ISSN: 1544-9173; 1545-7885

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.