Pain as a Trigger for Epigenetic Modifications in Limbic Circuitry
Chronic pain involves both central and peripheral neuronal plasticity that encompasses changes in the brain, spinal cord, and peripheral nociceptors. Within the forebrain, mesocorticolimbic regions associated with emotional regulation have recently been shown to exhibit enduring gene expression changes in models of chronic pain. To better understand how such enduring transcriptional changes might be regulated within brain structures associated with processing of pain or affect, we examined epigenetic modifications associated with active or permissive transcriptional states (histone H3 lysine 4 mono and trimethylation, and histone H3 lysine 27 acetylation) in periaqueductal gray, lateral hypothalamus, nucleus accumbens, and ventral tegmental area five weeks after sciatic nerve injury to model chronic pain. For mice in chronic pain, we observed an overall trend for a reduction of these epigenetic markers in the periaqueductal gray, lateral hypothalamus, and nucleus accumbens, but not the ventral tegmental area. Moreover, we discovered that some epigenetic modifications exhibited changes associated with pain history, while others were associated with individual differences in pain sensitivity. When taken together, these results suggest that chronic pain may lead to a suppression of transcription and gene expression in key limbic brain structures and circuits, which may ultimately result in maladaptive plasticity within these systems.