The paper document the first use of [11C]Martinostat, an HDAC-selective radiotracer, positron emission tomography to assess HDAC availability in chronic pain condition. Our data revealed a significant reduction of [11C]Martinostat binding in several brain regions associated with pain processing in patients with chronic back pain relative to controls.

Abstract

Epigenetics has gained considerable interest as potential mediators of molecular alterations that could underlie the prolonged sensitization of nociceptors, neurons, and glia in response to various environmental stimuli. Histone acetylation and deacetylation, key processes in modulating chromatin, influence gene expression; elevated histone acetylation enhances transcriptional activity, whereas decreased acetylation leads to DNA condensation and gene repression. Altered levels of histone deacetylase (HDAC) have been detected in various animal pain models, and HDAC inhibitors have demonstrated analgesic effects in these models, indicating HDACs’ involvement in chronic pain pathways. However, animal studies have predominantly examined epigenetic modulation within the spinal cord after pain induction, which may not fully reflect the complexity of chronic pain in humans. Moreover, methodological limitations have previously impeded an in-depth study of epigenetic changes in the human brain. In this study, we employed [11C]Martinostat, an HDAC-selective radiotracer, positron emission tomography to assess HDAC availability in the brains of 23 patients with chronic low back pain (cLBP) and 11 age-matched and sex-matched controls. Our data revealed a significant reduction of [11C]Martinostat binding in several brain regions associated with pain processing in patients with cLBP relative to controls, highlighting the promising potential of targeting HDAC modulation as a therapeutic strategy for cLBP.

Reference:
Yoo, C. H., Rani, N., Shen, S., Loggia, M. L., Gaynor, K., Moore, K. E., Bagdasarian, F. A., Lin, Y. S., Edwards, R. R., Price, J. C., Hooker, J. M., & Wey, H. Y. (2024). Investigating neuroepigenetic alterations in chronic low back pain with positron emission tomography. Pain, 10.1097/j.pain.0000000000003272. Advance online publication. https://doi.org/10.1097/j.pain.0000000000003272