Epigenetic understanding of pain mechanisms and modern treatment perspectives

Abstract

Human and animal research showed that environmental factors and lifestyle change ‘activate and deactivate’ gene expression due to epigenetic processes, which influences the perception of pain. Chronic and acute pain induce cellular memory of pain. It means that tissue lesion may cause epigenetic changes depending on the scale and kind of injury and conditions related to it. Cellular memory about pain may be transmitted to the cells of offspring through transgenerational transmission, thus inducing in further generations anxiety to neutral stimuli, related to the pain of their ancestors. In the same way, the consequences of excess opioid use may be transmitted to future generations, which is particularly dangerous, as the phenomenon of opioid abuse is becoming a serious threat to public health. It was proved that epigenetic changes in chronic pain occur in concrete genes in various diseases and conditions. Epigenetic changes also occur in genes influencing pain sensitivity. Changes in DNA methylation, histone modifications and non-coding RNA in regions related to pain, cause neuropathic, inflammatory and visceral pains. Epigenetic regulation of gene expression has recently been one of the most important objects in research on pain pathogenesis. The consequences are therapy trials with the use of DNA demethylation or reacetylation of histone lysine residues. In animal and human research, it was proved that the use of histone deacetylase inhibitors and DNA methyltransferase inhibitors decreases pain sensation. The research in the creation of new analgesics is promising. However, current epigenetic medications are highly nonspecific inhibitors that may have unknown side effects. Currently available knowledge does not allow yet to state whether they can be used in a long-term treatment of chronic pain.