Mapping the epigenetic signatures of pain

Pain must be correctly categorised for the right treatment to be prescribed; however, it is challenging for patients to define their pain, its intensity or even its location using questionnaires. To overcome this difficulty, scientists from the University of Geneva (UNIGE) have joined forces with the Clinique romande de réadaptation (CRR) to carry out a complete epigenomic analysis of patients, making it possible to find the epigenetic signatures specific to each pain category.

Chronic pain is classified into two main categories: nociceptive pain — defined by the activation of receptors at the end of nerve fibres and found in osteoarthritis, burns or infections — and neuropathic pain, which is caused by damage to nerve structures, such as pain caused by shingles. In order to classify which pain the patient suffers from, they fill in several questionnaires and quantify pain intensity using assessment scales. This is very subjective and time-consuming.

“At the CRR, we treat many people suffering from chronic diseases,” said researcher Bertrand Léger. “We joined forces with UNIGE scientists to carry out a complete epigenomic study and define specific biomarkers for each type of pain, in order to be able to categorise the various types of pain quickly and reliably.”

To do this, the Geneva team carried out an analysis of the entire genomes of 57 patients: 20 with no pain, 18 with nociceptive pain and 19 with neuropathic pain. As explained by UNIGE Professor Ariane Giacobino, “The aim was to start without any prior hypothesis to probe the genome as a whole and identify all the biomarkers involved in pain.”

Not only did the scientists identify very striking epigenetic signatures of pain, they also found no overlap between nociceptive and neuropathic pain. Prof Giacobino said, “This total absence of similarities between the two categories of pain is very surprising, because intuitively, we might think that the difficulty in defining one’s pain comes from a similarity in the epigenetic signature. We could prove that it is absolutely not the case.”

Indeed, the biomarkers specific to nociceptive pain are expressed by the genes of the opioid system — involved in emotion, reward and pain — as well as by the genes of inflammation, specific to irritation. Conversely, the biomarkers for neuropathic pain are linked only to genes of the GABA system, the neurotransmitters of the central nervous system. The results were published in The Journal of Pain.

“Now that these epigenetic signatures are clearly defined, a simple blood test will make it possible to define the type of pain the person is suffering from and prescribe the appropriate treatment,” Léger said. The treatment will thus no longer target the symptoms, but the very root of the problem — and since epigenetics is characterised by the fact that the expression of a gene is durably modified, the right treatment may return it to normal.

“We could imagine monitoring the reversion of pain by observing, from an epigenetic point of view, whether the biomarkers return to normal, and adapt the treatment accordingly,” Prof Giacobino concluded.

Image credit: ©stock.adobe.com/au/pankajstock123

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