Targeting epigenetic mechanisms for chronic visceral pain: A valid approach for the development of novel therapeutics.

Abstract

Chronic visceral pain is persistent pain emanating from thoracic, pelvic, or abdominal origin that is poorly localized with regard to the specific organ affected. The prevalence can range up to 25% in the adult population as chronic visceral pain is a common feature of many visceral disorders, which may or may not be accompanied by distinct structural or histological abnormalities within the visceral organs. Mounting evidence suggests that changes in epigenetic mechanisms are involved in the top-down or bottom-up sensitization of pain pathways and the development of chronic pain. Epigenetic changes can lead to long-term alterations in gene expression profiles of neurons and consequently alter functionality of peripheral neurons, dorsal root ganglia, spinal cord, and brain neurons. However, epigenetic modifications are dynamic, and thus, detrimental changes may be reversible. Hence, external factors/therapeutic interventions may be capable of modulating the epigenome and restore normal gene expression for extended periods of time. The goal of this review is to highlight the latest discoveries made toward understanding the epigenetic mechanisms that are involved in the development or maintenance of chronic visceral pain. Furthermore, this review will provide evidence supporting that targeting these epigenetic mechanisms may represent a novel approach to treat chronic visceral pain.