A woman who does not feel pain could be the key to the development of painkillers and new treatments

Stay in a state of constant well-being. It seems like a utopian situation but Joanne Cameron, a 75-year-old woman from Scotland, is lucky enough to live that way. A modification in the expression of the FAAH gene, producer of an enzyme that processes endocannabinoids and causes them to be absorbed in the body, is related to this.

Levels of anandamide, a substance with marijuana-like effects, are higher than normal in Cameron's body. So, your levels of anxiety, stress or pain are much lower.

"This makes me ridiculously happy," she told Spain's El Pais newspaper.

His case seems to be the key to the development of painkillers without the addictive risk of opioids, according to the Spanish newspaper.

The case of Jo Cameron, the woman who does not feel pain, could be the key to developing painkillers.

Cameron's story reached pain geneticists at University College London (UCL) in 2013 after his doctors realised he was pain-free after two complex operations, one on the hip and one on the hand.

From that moment on, investigators try to understand what makes Cameron special. The idea, with this analysis, is to help millions of people who live with chronic pain and anxiety and, so far, must resort to medications that generate addiction.

New study

Recently, the journal Brain published a work led by Andrei Okorokov and James Cox, from UCL, in which the researchers detailed some of Cameron's particularities.

One in three people have mutated the FAAH gene and higher levels of anandamide, but not everyone enjoys the protection that this Scottish woman has. This has to do with the fact that she has another rare mutation in the FAAH-OUT gene, which is found in what was known as junk DNA, a part of the genome that was considered useless because it does not produce proteins.

In recent years, it was discovered that these genes influence how genes that do produce proteins are expressed. That interaction explains Cameron's case.

"The FAAH-OUT gene is a small corner of a vast continent that this study has begun to map," said Okorokov, one of the researchers.

In addition to identifying the molecular basis of the absence of pain, this work found the way in which the mutation of this gene improves mood or facilitates the healing of wounds, according to the Spanish newspaper.

For Okorokov, "these findings will have important implications for areas of research such as wound healing or depression."

The researchers observed that, in addition to reducing the activity of the gene responsible for removing endocannabionides from the blood, there are 348 other attenuated genes, but also 797 intensified ones. Among them is WNT16, related to bone regeneration, or BDNF, which influences mood.

Javier Fernández, director of the cannabinoid research group at the Complutense University of Madrid, said that these results "open the possibility of intervening directly on this regulatory process."

The researcher stressed that, from a practical point of view, it is still science fiction, "because it is difficult to bring this type of agent to the sites where they are going to be useful and, in many cases, they are very ubiquitous enzymes or proteins, so such a tool can affect many things and have side effects." However, he assured that "it is a good guide for the future."

Although Fernández acknowledges that the potency of cannabinoids to combat pain is lower than that of opioids, he recalls that "they are also much safer."

According to the researcher, one way to take advantage of these synergistic effects would be to combine a lowdose, which alone would have no effect, of an opioid, with another reduced dose of a cannabinoid. "With that combination, the same effects would be obtained as the opioids used now, but without the problems of the epidemic due to the use of these drugs that has been seen in the United States and is now beginning to be seen in Europe," he explained.

Meanwhile, Andrés Ozaita, professor of Pharmacology at Pompeu Fabra University, said that the knowledge obtained with the study of people like Joanne Cameron can lead to therapies that change the way we understand the treatment of pain.

"Knowing these mechanisms of gene expression, new approaches can be proposed, such as gene therapy for people with chronic pain," Ozaita added.

This type of therapy would consist of the transfer of genetic material to change the expression of some genes of patients and make them more similar to that of people like Cameron.

Although Cameron is a person with less anxiety and pain than average, she herself acknowledged in 2019 that her mutations not only offer advantages: "I burn often in the kitchen and I don't find out until it smells like burnt meat. I have a lot of scars on my body."

"It's not a good thing. This has its advantages and disadvantages. The pain warns you that something bad is happening and I don't know about it," he warned.

SC