Marked by pain

Chronic pain can be marked in the DNA

The work was published in the open-access journal PlosOne. To model pain, scientists injured nerves in the tight of laboratory mice through surgery. The purpose of the study? To understand if the lesion remains in the DNA of cells as a mark.

The research showed that epigenetic marks can be found in the DNA of cells from brains of mice suffering from chronic pain. Epigenetics comprises the chemical marks in the DNA and associated proteins that are the product of signals and stimuli arising from different sources. In the same way as each cell is characterized by its genes (genetics), it is now clear that cells are also characterized by the chemical modifications in those genes (epigenetics). Even if epigenetics cannot change the sequence of genes in the DNA molecule, it can control the way genes are "read". In this experiment, peripheral nerve injury led to epigenetic alterations in the brains of the mice, at the level of DNA, as if to remind the animals of the lesion suffered 6 months before.

credits: Ana Costa
A new system for quantifying pain can
originate from the new observations.  

 It is not clear yet which consequences originate from the epigenetic marks in specific regions of the brain. To better understand the mechanism observed, scientists induced symptom relief, to some extent, by means of exposing the mice to modified cages (a procedure somehow similar to a series of physiotherapy sessions). The changes in the symptoms were associated with changes in the epigenetic marks of the DNA molecule in the brain cells. Scientists learnt that the marks in the DNA could be related by the levels of pain.

In the future, will this information be useful to those patients suffering from chronic pain, regardless of its cause? The authors of this study are optimistic about the future and believe that one day it will be possible to treat pain if the epigenetic marks in the DNA are modulated by clinicians. And even if the treatment of pain is far from reality, these new observations can start by serving another purpose: that of quantifying pain. Currently, assessing pain in complex due to subject to subject variability. However, establishing a more objective method of quantification could be beneficial for the correct diagnosis and treatment of various pathologies. This new study can be the basis for a new, epigenetics-based, quantification method for pain.

Epigenetics of cancer

Cancer signatures extend to epigenetic marks. Credits: Ana Costa

Cancer's new signatures:

Epigenetic modifications are conserved among various metastases in the same person.

Today’s EpiPost focuses on a new discovery concerning prostate cancer and its metastases. The report published in Science Translational Medicine (23rd January 2013 ) highlights the need for personalized medicine by showing that the patterns of epigenetic modifications vary considerably between lethal prostatic tumours from different men but are maintained within the tumour and metastases in the same person.

Epigenetics is the layer of genomic regulation that is not due to the sequence of As, Ts, Cs and Gs in the DNA molecule, but instead relies on chemical marks found in nuclear DNA and its associated proteins. These epigenetic marks that sit on DNA, namely the methylation mark, are very relevant from the point of view of physiology, as they may shape to the way cells responds to stimulus, both from outside, and from inside the cell itself. In recent years, scientists have observed that tumours display their own patterns of DNA methylation and those differ from the ones found in the “normal” cells of the same person. This observation led to the question: can DNA methylation be used as a diagnostic biomarker for cancer?

So far, the general belief that DNA methylation patterns varied too much in each patient's widespread cancers procrastinated the development of diagnostic strategies or even therapies. Now, with the help of new biochemical and computational technologies, scientists from the Johns Hopkins University, in Baltimore, USA, made two seminal observations that may change this view: first, that the DNA methylation patterns were considerably altered between tumours from different individuals; and second, that tumours and metastases from the same individual had identical DNA methylation patterns. For this analysis, the samples were obtained from autopsies of men who had died of metastatic prostate cancer. Both samples from the various metastases, as well as samples from normal tissues were collected for genomic comparisons.

The results led the scientists to conclude that each cancer evolves to acquire its own characteristic signature of DNA modifications, and that this epigenetic signature is maintained at sites of metastases. This observation has a close parallel to what is known about genetic alterations of tumours, which are also stable within each individual. As with genetic alterations that contribute to the onset and dissemination of cancer, epigenetic changes are also to be taken into account when investigating the events leading to cancer progression.

The new data revealed that new biomarkers of aggressive cancers lie in the epigenetic landscapes of each patient’s cancer cells. Scientists believe that this knowledge will help in the early identification of these forms of cancer and may possibly contribute to the development of therapeutic strategies directed at each person’s specific cancer epigenetic signatures. 

From the brains of the bees

Of bees and…

credits: Ana Costa

From the brains of honeybees, we learned that epigenetics can control social behaviour and career changes.

EpiPost

Epigenetics…let’s get started.

The text below refers to laboratory results published back in 2011. However, those results are a good example of what epigenetics can mean to our lives. If, after reading the post, you’re more confused than before, don’t worry – even senior scientists working in this field for a long time can be surprised by the experimental results related with epigenetics!

I am writing about a paper published more than a year ago to start a new series called: EpiPosts. More to come soon – how can we resist this topic?!