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Identification of FAM173B as a protein methyltransferase promoting chronic pain
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Date
2018
Author
Willemen, Hanneke L. D. M., Kavelaars, Annemieke, Prado, Judith, Maas, Mirjam, Versteeg, Sabine, Nellissen, Lara J. J., Tromp, Jeshua, Gonzalez Cano, Rafael, Zhou, Wenjun, Jakobsson, Magnus E., Małecki, Jędrzej, Posthuma, George, Habib, Abdella M., Heijnen, Cobi J., Falnes, Pål Ø., Eijkelkamp, Niels
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Abstract
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.