Researchers have studied people who are genetically ‘pain insensitive’, in order to identify new analgesic strategies for treating chronic pain.
The overuse of opioid-based drugs to treat pain is leading to an opioid epidemic in several countries, write Dr Andrei Okorokov of University College London, UK, and colleagues in today’s Brain.
“Poorly treated chronic pain therefore makes life intolerable for extreme numbers of people and new painkilling medications are hence urgently needed,” they add.
So, the team looked at people with a rare genetic mutation that allows the individual to live virtually pain-free and heal more rapidly.
The authors previously identified the ‘FAAH-OUT’ gene and have now found that it turns down expression of this gene and impacts other molecular pathways linked to wound healing and mood.
They report that the FAAH-OUT gene regulates a related endocannabinoid system gene.
“We have uncovered a network of genes that are dysregulated from disruption of the FAAH-FAAH-OUT axis, thus providing a coherent mechanistic basis to understand the human phenotype observed and a platform for development of future gene and small molecule therapies,” they write.
Dr Okorokov said: “As well as the molecular basis for painlessness, these explorations have identified molecular pathways affecting wound healing and mood, all influenced by the FAAH-OUT mutation.
“As scientists it is our duty to explore and I think these findings will have important implications for areas of research such as wound healing, depression and more.”
Co-author Professor James Cox added: “By understanding precisely what is happening at a molecular level, we can start to understand the biology involved and that opens up possibilities for drug discovery that could one day have far-reaching positive impacts for patients.”
Mikaeili, H. et al. Molecular basis of FAAH-OUT-associated human pain insensitivity. Brain 24 May 2023; doi: 10.1093/brain/awad098
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