Chronic pain causes epigenetic changes in the brain and immune system

This 2015 Canadian rodent study by McGill researchers found:

“The critical involvement of DNA methylation in chronic pain. We show that in the PFC [prefrontal cortex], a brain region strongly implicated in chronic pain, a stunning number of promoters [control gene expression] are differentially methylated 9 months after injury. These changes are distant both in time and space from the original injury.

The changes in DNA methylation are highly organized in functional pathways that have been implicated in pain such as dysregulation of dopaminergic, glutamatergic, opioid and serotoninergic systems and important signaling and inflammatory pathways.

Genome-wide DNA methylation modifications of T cells [circulating white blood cells that control immune response] are also associated with nerve injury.

Most of the promoters (72%) identified as differentially methylated in T cells after nerve injury were also affected in the brain. While the methylation profiles in some of these modules were affected in the same direction in the brain and the T cells, others went in opposite direction. This is consistent with the idea that the brain and the immune system play different roles in chronic pain.

These data suggest that persistent pain is associated with broad and highly organized organism-wide changes in DNA methylation, including two critical biological systems: the central nervous and immune systems. This work also provides a possible mechanistic explanation for commonly observed comorbidities observed in chronic pain (i.e anxiety, depression). Finally, the sheer magnitude of the impact of chronic pain, particularly in the prefrontal cortex, illustrates the profound impact that living with chronic pain exerts on an individual.”


The news coverage focused on how the study’s findings may lead to non-invasive DNA methylation measurements of chronic pain as well as treatments of the effects. I’d argue that the researchers’ concluding statement of the Discussion section deserved the most focus:

“Beyond the example of chronic pain, the robust and highly organized DNA methylation changes seen here in response to nerve injury provides some of the strongest evidence to date that experience effects DNA methylation landscapes at large distances in time and space.”

The study provided¬†“some of the strongest evidence to date” that experiences caused widespread, long-lasting epigenetic changes. Given experiences’ etiologic functions, research with working hypotheses that experiences may also reverse epigenetic changes should be green-lighted.

“DNA methylation landscapes at large distances in time and space” warrant systematic examination of how experiential epigenetic changes during early life may be reversed by experiential therapies later in life. In 2016, there’s sufficient evidence for modifying research goals to primarily address causes, not just effects.

http://www.nature.com/articles/srep19615 “Overlapping signatures of chronic pain in the DNA methylation landscape of prefrontal cortex and peripheral T cells”

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