Mysterious pain

After living for 71 years, Jo never knew what it was like to feel pain: she didn’t use an anesthetic when she gave birth to a child. “It feels like itching.” She is often cut and burned, but her wounds always seem to recover. Soon; she suffered from severe joint disease that affected walking, but she never felt anxious or panicked. People like Jo, less than one in every one million people, are generally characterized by their own painkillers.

Double cannabinoid

The University of London research team sequenced the DNA of Jo and his family, eventually locking the FAAH (fatty acid amide hydrolase) gene.

The enzyme encoded by the FAAH gene is capable of decomposing an endogenous cannabinoid. As the name implies, this substance is similar to the active ingredients of cannabis, and it can provide a feeling of relaxation and is closely related to pain perception, emotion and memory.

Specifically, Jo carries two mutations. These two mutations work together to completely inactivate the FAAH gene in Jo. Without the enzyme that breaks down it, the endogenous cannabinoid AEA in Jo continues to accumulate, reaching twice the level in the blood. This also explains why Jo’s level of anxiety is so low.

The research team believes that Jo may have inherited such mutations from his father. Her father almost never took painkillers during her lifetime, and her mother and daughter had normal pain. Her son is also less sensitive to pain and is often burnt by hot drinks or food, but the situation is not as extreme as her.

Mysterious pain

Today, when brain science is so developed, pain is still one of the most mysterious feelings of human beings. Scientists still have not found the so-called “painful brain area” because pain activates activities in different brain areas, including feelings, emotions, cognition, decision making, and brainstem.

Pain insensitivity may be caused by mutations in different genes. This situation can be roughly divided into two categories: some people have an overall developmental abnormality in the nervous system associated with pain, and the other part of the human nervous system is mostly intact, but the pain receptors are inoperable.

Diseases caused by inability to work with pain receptors are called congenital analgesia. According to data from the National Institutes of Health, there are currently only about 20 cases documented. This disease is mainly caused by genetic mutations, which are found in pain receptors and olfactory neurons. Therefore, most patients with congenital analgesia completely lose their sense of smell. Other studies have shown that patients who retain their sense of smell carry another mutation, and they also have symptoms of excessive sweating.

In contrast, diseases caused by abnormalities in the relevant nervous system are more complicated. For example, a type of congenital painless and sweat-free disease is also caused by genetic mutations. These patients not only completely lost their pain, but also were not sensitive to temperature (including temperature perception and body temperature regulation), and many people also had symptoms such as mental retardation.

Due to impaired thermoregulatory capacity, congenital painless and sweat-free patients have a higher risk of dying from fever or heat stroke than the general population.

Painless drawback

The painless feeling brought some inconvenience to Jo. Because there is no pain, Jo often cannot find himself injured in time. For example, when she is burnt, she often smells the barbecue first, and then finds out what is wrong. There are also many people who are not sensitive to the pain and who suffer from serious bone or joint diseases because they cannot detect early symptoms in time.

Jo may not be able to enjoy the feeling of eating spicy. Spicy is actually a pain, but for Jo, it is just a “pleasant burning sensation.”

In addition, perhaps because of the close relationship between memory and emotion, Jo has long been very forgetful. She often forgets the following half of the words, or forgets where to put the keys.

Today, with the growing problem of painkillers, cases like Jo have important implications for the medical community. Scientist James Cox said: “We can learn a lot from her. Once we understand how this newly discovered gene works, we can explore new gene therapies and mimic the workings of genes in her. Millions of people endure With the pain of pain, we need new painkillers. Patients like Jo can give us a new understanding of the pain system.”