Jo Cameron, a 75-year-old Scottish woman, possesses an extraordinary ability to live without experiencing significant pain throughout her life. Even major surgeries and childbirth failed to deliver the discomfort most people would normally feel. Cameron's rare condition, known as congenital analgesia, is shared by only a few individuals worldwide. With multiple genetic causes, this one-in-a-million anomaly may present additional symptoms such as a lack of sense of smell or excessive sweating.
Scientists at University College London (UCL) are currently studying Cameron's genes to unravel the mechanisms that can deactivate pain pathways in individuals with chronic pain conditions. While pain serves as a crucial indicator of bodily harm, it can sometimes become stuck in an overactive state that no longer serves a beneficial purpose. Chronic pain, lasting beyond a few months, poses significant challenges. Cameron's genetic makeup may hold the key to understanding and potentially alleviating this suffering.
By delving into the molecular level of her condition, researchers aim to gain insights into the underlying biology, paving the way for future drug discoveries that could greatly benefit patients. The specific variation in Cameron's FAAH-OUT gene, discovered and named by UCL pain geneticist James Cox and his team in 2019, plays a pivotal role in modulating the FAAH gene. FAAH, also known as the "happy gene" or "forgetful" gene, tends to reduce anxiety and enhance absentmindedness.
Cameron's FAAH-OUT mutation, in combination with a more common variant in a neighboring gene, results in her inability to experience even the surge of adrenaline in fearful situations, such as car crashes. Researchers have attempted to develop drugs targeting FAAH over the past two decades, but none have successfully passed human clinical trials. Understanding the interplay between FAAH and FAAH-OUT could refine these efforts and deepen our understanding of pain.
The latest study by Cox and his colleagues reveals that both genes are frequently co-expressed in the same cells. Further experiments mimicking Cameron's condition showed that silencing or editing FAAH-OUT in lab-grown human cells led to reduced expression of FAAH. Consequently, this affected genes related to pain and opioid receptors, wound healing lipids, and brain proteins involved in mood modulation.
"The FAAH-OUT gene is just one small corner of a vast continent, which this study has begun to map," says molecular biologist Andrei Okorokov from UCL. "These explorations have identified molecular pathways affecting wound healing, mood, and pain, all influenced by the FAAH-OUT mutation. These findings will have important implications for research areas such as wound healing and depression."
It wasn't until Cameron turned 65 that she realized how distinct her experience of life was compared to most individuals. Now, her unique cellular secrets hold promise for a happier and less painful existence for many others.