Epigenetics and the autonomic nervous system: what is their role in chronic pain?   May 21st, 2022

The word “epigenetics” can be split in “epi” and “genetics” - “epi” means on and “genetics” refers to DNA - so epigenetics refers to molecules that are attached on our DNA. These molecules change the readability of the manual of our body and thus impact all body functions. What is interesting about epigenetics, is that it can be influenced by several factors, for example lifestyle and environmental factors.

From epigenetics via dysautonomia to chronic pain

One body function that can be impacted by epigenetics is the autonomic nervous system (ANS). For instance, epigenetic mechanisms can impact the readability of the manual giving instructions about the enzymes that regulate the concentrations of the messengers (e.g. catecholamines) of the ANS. If those epigenetic mechanisms are disturbed, this can lead to a dysregulation in the balance between the sympathetic and parasympathetic part. This dysregulation is called dysautonomia.

In turn, dysautonomia is linked to several things that could lead to the induction and/or maintenance of chronic pain. For example, the ANS is involved in the release of pro- and anti-inflammatory cytokines and thus interacts with inflammation. This interaction is reflected by the inverse relationship between heart rate variability and various inflammatory markers. Dysautonomia due to decreased activity of the vagal nerve in the cholinergic anti-inflammatory pathway may lead to chronic inflammation. And pain is one of the five cardinal signs of inflammation.

Another way through which dysautonomia has an effect on pain is via the baroreflex. Activation of the baroreflex, which is triggered via an increase in blood pressure in turn regulated via the ANS, is namely associated with a global inhibitory effect on the brain. As a result, there is an inverse relation between blood pressure and pain sensitivity. Dysautonomia can thus result in an increased sensitivity to painful stimuli via its effect on the baroreflex.

A higher sensitivity to the development of inflammation and increased sensitivity to painful stimuli can thus contribute to the development of pain or even chronic pain when dysautonomia lasts.

What can lifestyle do?

Your epigenetic profile is built by all experiences throughout your entire life. Stress is one of the factors that shapes your epigenetic profile from very early on. It has been shown that stress increases DNA methylation - one of the best known epigenetic mechanisms - on genes encoding for the enzymes regulating catecholamine levels. In one of our recent studies (unpublished data), we showed that patients with chronic pain already have increased DNA methylation on such genes. It is thus important to eliminate stress as much as possible in order to prevent a further increase in DNA methylation on those genes and enhance dysautonomia. Similar to stress, tobacco smoking also increases DNA methylation on those genes and can thus increase one’s susceptibility to develop dysautonomia and chronic pain.

Lifestyle factors can therefore have an impact on chronic pain mechanisms. Physical activity for example will decrease pain sensitivity and leads to a more effective ‘muscle pump’ (by increased blood volume and muscle tone), decreased cardiac sympathetic and increased vagal activity, lower blood pressure, and increased stroke volume. The latter factors indicate an improved function of the ANS.

Lifestyle factors clearly have a major impact on both epigenetics and the ANS. Improving your lifestyle can thus positively impact biological mechanisms that may be involved in the maintenance of chronic pain and eventually help with managing symptoms.

Jente Bontinck, Jolien Hendrix, Michel Mertens, Yannick Tobbackx

2022 Pain in Motion

References and further reading: