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.
Original language | English |
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Pages (from-to) | e2003452 |
Journal | PLoS Biology |
Volume | 16 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2018 Feb |
Externally published | Yes |
Subject classification (UKÄ)
- Biochemistry and Molecular Biology
Free keywords
- Animals
- Chromosomes, Human, Pair 5
- Chronic Pain/enzymology
- Female
- Gene Knockdown Techniques
- Genome-Wide Association Study
- HEK293 Cells
- Histone-Lysine N-Methyltransferase/genetics
- Humans
- Male
- Mice, Inbred C57BL
- Microglia/metabolism
- Polymorphism, Single Nucleotide
- Reactive Oxygen Species/metabolism