Figure 4.

Epigenetic regulation of chronic stress-induced visceral pain. Epigenetics describes the processes by which the environment influences gene expression to cause persistent changes in behaviors. Stressors (early life stress, adult stressors, or both) induce changes in the methylation status of DNA promoter regions to enhance or repress transcription rates. Stressors also change the state of histone acetylation around the gene promoter regions to facilitate or hinder the binding of the transcription complex, which also affects gene transcription. These stress-induced changes in DNA methylation and histone acetylation cause changes in gene expression that persist well beyond the duration of the stressor. Additionally, due to hormonal differences across the lifespan, sex differences in response to stressors can also modify the epigenetically induced changes in gene expression. The net effect is the development of chronic visceral pain following stressors that persist through the individual's lifetime due to epigenetically induced changes in gene expression leading to enhanced neuronal sensitivity.