Genetic mutation enhances the functioning of the endocannabinoid system, which blocks pain
Some rare and very happy families have inherited insensitivity to pain. From cuts and burns to usually painful hand surgeries, some people experience no pain. In the case study, “Microdeletion in an FAAH pseudogene identified in a patient with high anandamide levels and insensitivity to pain,” a 66-year-old woman with this rare disorder was examined and the researchers were amazed at what her DNA revealed.
The woman who feels no pain
In this case, it was found that the pain-insensitive patient has a genetic disorder that causes a deficiency in the function of fatty acid amide hydrolase (FAAH). Doctors were surprised after she underwent hand surgery and had no post-operative pain. Also, in her previous medical interventions, including hip replacements and dental work, she did not need pain relievers (analgesics) and had quick healing without pain when it came to cuts and burns. She could even eat extremely hot peppers with no discomfort! Even more surprising is that she has not experienced any anxiety or depression and says that she does not panic in dangerous or anxious situations.
FAAH Mutation Enhanced Endocannabinoid Signaling
The researchers decided to examine the patient’s DNA and found that a deletion mutation on chromosome 1 was inherited from her father, who also had no pain sensation. This inheritable DNA deletion means that your FAAH enzymes won’t break down complex molecules into simpler ones as they should. FAAH normally breaks down fatty acid amides (FAAs) like anandamide (AEA), which are part of the endocannabinoid system (ECS). AEA is like the natural version of the cannabinoid tetrahydrocannabinol (THC) and also affects how the ECS sends messages about pain and fear to the body.
New goals for drug development
The ECS helps regulate body functions such as pain perception and fear perception. Mice that lack a functioning FAAH, like the patient, have increased AEA blood concentrations, improved endocannabinoid signal transmission, rapid wound healing and a poor sense of pain. This has made FAAH inhibitors an exciting target for drug development. Previous attempts were unsuccessful, but this new genetic information may allow researchers to make progress in the future.
Picture: https://unsplash.com/photos/NFvdKIhxYlU from the National Cancer Institute on Unsplash
- Habib AM, Okorokov AL, Hill MN et al. Microdeletion in an FAAH pseudogene identified in a patient with high levels of anandamide and insensitivity to pain. British Journal of Anesthesia. 2019; 123 (2): e249-e253. doi: 10.1016 / j.bja.2019.02.019 Accessed on April 5, 2021. https://www.sciencedirect.com/science/article/pii/S0007091219301382