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People's main senses correspond to five senses: eyes (vision), ears (hearing), nose (smell), tongue (taste) and skin (touch). But in fact, there are feelings in other organs of the body, and unfortunately, this feeling is usually pain and means that there is something wrong with the body's organs. It can be said that this "sixth sense" is not miraculous, but a research direction that is expected to reveal the pathological mechanism of various organs of the human body and explore the corresponding means of prevention and treatment.

Wen Jing | Wen Jing

When a person encounters something that puts him in a bad mood, he often has a bad appetite. Some people often go to the toilet when they encounter exams, interviews, appointments, public speeches and other things that make them nervous. When we go through these things, there is always a wonderful feeling that the stomach and intestines are controlled by the brain. In fact, there is a gut brain, and the latest research also reveals the connection between the gut and the brain.

The second brain and its contact brain with the "first brain" mainly include cerebrum and cerebellum, with a total of about 86 billion nerve cells (about 14 billion ~ 16 billion nerve cells in the cerebral cortex and 55 billion ~ 70 billion in the cerebellum). The human brain can be said to be the highest part of the human nervous system, but some scientists believe that there are actually "two brains" in our bodies: one is the traditional human brain, and the other is the intestinal tract, also known as the "intestinal brain" or "second brain".

Studies have shown that there are about 500 million nerve cells in the gut (including multistage ear cells, ganglion cells in the sympathetic chain or gastrointestinal plexus). This number is second only to the total number of nerve cells in the central nervous system. The gut brain can operate independently and can communicate with the central nervous system in both directions.

However, in fact, the concept of enteric brain has not been put forward for a long time, and scientists' exploration of the communication mechanism between it and the central nervous system is limited. At present, it is mainly believed that there are three ways of communication.

Vagus nerve: the nerve cells between the central nervous system and the gut brain are connected by the vagus nerve. The vagus nerve can transmit information in both directions.

Neurotransmitters: studies have shown that the intestinal nervous system produces 50% of the body's dopamine and about 90% of serotonin (serotonin). These neurotransmitters can act on the brain and are very important for mood regulation. On the contrary, neurotransmitters produced by the central nervous system also act on the gut brain. In addition, intestinal flora can produce a neurotransmitter called gamma-aminobutyric acid (GABA), which can help us control emotions such as fear and anxiety.

Third, other chemicals produced by intestinal flora, such as acetic acid, propionic acid and butyric acid, can also stimulate nerve cells, and the electronic signals produced by these stimuli can be transmitted to parts of the brain.

In order to have a better understanding of the enteric brain and develop more methods for the treatment of neurological diseases, it is also necessary to explain the mechanism between the enteric brain and the central nervous system more clearly.

Nerve cells in the colon that experience different stimuli, researchers at Harvard Medical School recently published an article in Cell, defining for the first time five different sensory nerve cells that transmit signals to the brain in the colon. These cells can respond to different forms of stimulation, including small, mild forces, as well as strong stimuli.

The researchers first explored the communication between sensory nerve cells in the skin and the brain to understand the process of tactile formation. They developed precise tools to label different types of sensory nerve cells and used these tools to reveal basic information about the structure, organization and function of skin sensory nerve cells.

The researchers then tried to apply a similar method to other organs such as the colon. In the new study, the researchers used a genetically labeled mouse model to simulate the slight stretching that might occur when food or feces passed through the colon, recording which nerve cells became active after different levels of stimulation.

After identifying the nerve cells corresponding to different levels of stimulation, the researchers artificially activated nerve cells that were sensitive to high-intensity stimuli, and the mice showed a pain-like response; after the nerve cells sensitive to high-intensity stimuli were artificially removed, the pain response of the mice weakened.

In addition, experiments have shown that if the mice have an inflammatory response, one of the pain-sensing nerve cells becomes more sensitive. In other words, the intestines may be more "fragile" when the mice get sick. This is a noteworthy phenomenon because inflammation is a major source of pain in patients with inflammatory bowel disease.

Although the current research is still in the experimental stage of mice, the researchers believe that this finding is expected to provide ideas for the study of better treatments for different gastrointestinal diseases. For example, studying nerve cells sensitive to low-intensity stimuli can help deal with intestinal movement-related diseases such as constipation and diarrhea, while studying nerve cells sensitive to high-intensity stimuli can help deal with pain originating in the colon.

In addition to irritations such as mild stretching and inflammation of the colon, the researchers also plan to study other stimuli that may cause abdominal pain (such as toxins or insufficient blood flow), and will also study other parts of the gastrointestinal tract.

References:

DRG afferents that mediate physiologic and pathologic mechanosensation from the distal colon. Cell (2023). DOI: https://doi.org/10.1016/j.cell.2023.07.007

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