Genetic Mutation Enhances Endocannabinoid System Function Blocking Pain
Some rare and very lucky families have inherited pain insensitivity. That’s right, from cuts and burns to normally painful hand surgeries, some people don’t feel pain. In the case study “Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity,” a 66-year-old female with this rare condition was evaluated and researchers were amazed by what her DNA revealed.
The Woman Who Doesn’t Feel Pain
In this case, the pain-insensitive patient was found to have a genetic disorder causing a lack of function of fatty-acid amide hydrolase (FAAH). Doctors were surprised after she underwent a hand surgery and exhibited no postoperative pain. In her previous medical procedures, including hip replacement and dental work, she also did not need pain killers (analgesics) and had fast healing without pain when it came to cuts and burns. She could even eat extremely spicy peppers with no discomfort! Even more surprising, she has not experienced anxiety or depression and says she does not panic in dangerous or fearful situations.
FAAH Mutation Enhanced Endocannabinoid Signaling
Researchers decided to study the patient’s DNA where they found that a deletion mutation on Chromosome 1 was inherited from her father who also had lack of pain sensation. This inheritable DNA deletion means that her FAAH enzymes do not break down complex molecules into simpler ones, as they should. FAAH normally breaks down fatty-acid amides (FAAs) such as anandamide (AEA) that are part of the endocannabinoid system (ECS). AEA is like the natural version of the cannabinoid tetrahydrocannabinol (THC) and likewise influences how the ECS communicates messages to the body about pain and fear.
New Targets for Drug Development
The ECS helps regulate body functions such as pain perception and fear perception. Mice that lack functioning FAAH, like the patient, have elevated blood concentrations of AEA, enhanced endocannabinoid signaling, fast wound healing, and lack of pain sensation. This has made FAAH inhibitors an exciting target for drug development. Previous attempts have been unsuccessful, but with this new genetic information, researchers may be able to make progress in the future.
Image: https://unsplash.com/photos/NFvdKIhxYlU by National Cancer Institute on Unsplash
References
- Habib AM, Okorokov AL, Hill MN, et al. Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity. British Journal of Anaesthesia. 2019;123(2):e249-e253. doi:10.1016/j.bja.2019.02.019 Accessed 05 April 2021. https://www.sciencedirect.com/science/article/pii/S0007091219301382
