Pain perception is one of the basic senses of human beings and higher animals. Its function lies in making the organism benefit and avoid harm and keep away from risk.
But in many cases, chronic and long-term severe pain has not only lost the significance of warning of danger, but also will bring great physical trauma and psychological pressure to patients.
On March 10, researchers at the University of California, San Diego, published a paper on gene therapy for pain in the journal Science Translational Medicine.
The study found that modifying the pain gene in mice with gene therapy can reduce the pain perception in mice for a period of time, and does not permanently disable the pain sensing system.
The results in mice suggest that chronic pain, which affects quality of life in humans, could be overcome by cutting-edge gene therapy.
How do traditional painkillers work?
Each of us may experience severe chronic pain at some point in our lives. Pain not only causes pain to the patient, but also adversely affects the central nervous system, circulation, respiratory, endocrine, digestive and autonomic nervous systems.
According to a survey conducted in the United States in 2018, 20 percent of American adults experience chronic pain and 8 percent say it has seriously affected their normal life.
Physical pain usually refers to the discomfort caused by physical injury, illness or adverse external stimuli.
Pain is a common or major symptom of many diseases, such as headache caused by brain tumors, chest pain caused by coronary heart disease, biliary colic and abdominal pain caused by gallstones, and cancerous pain in patients with advanced tumors.
Some pain is a disease in itself, such as herpes zoster neuralgia and trigeminal neuralgia.
Like other sensory systems in the body, pain is generated by the coordination of pain receptors located throughout the body and the central nervous system, such as the brain.
For example, when we accidentally touch a hot stove, pain receptors located in the skin will send the external stimulus through the nervous system to the brain, where the pain center of the brain will form a “pain” sensation.
Pain receptors throughout the body work with the central nervous system, such as the brain, to create pain.
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Sometimes, even though pain receptors throughout the body don’t actually feel pain, there’s damage to the nervous system that’s responsible for transmitting pain signals, and pain can form in the brain. This is neuropathic pain.
In addition to the above two kinds of pain, there is a relatively rare pain called psychogenic pain.
This kind of pain is the central nervous system has the pathological change, causes the patient to appear the painful feeling without the pain stimulation circumstance.
At present, the human to pain is not completely countermeasure, all kinds of painkiller is undoubtedly one of the greatest inventions in human history.
But common home pain relievers only relieve mild pain and only last for a few hours.
The opioid painkillers, which are used to relieve severe pain in clinic, have serious side effects such as addiction.
Moreover, as the body becomes more and more adaptable to the drug, the effectiveness of the treatment will decrease significantly over a period of time.
The root cause is that many traditional painkillers act directly on the central nervous system of the human body. Therefore, while affecting the pain center, they will also interfere with the normal function of other centers, causing side effects such as vomiting, lethargy, constipation, dizziness and even cramps.
Addiction and tolerance are also related to their action on the central nervous system.
So, is there a way to avoid the impact on the central nervous system and make the pain disappear completely within a certain period of time without affecting other bodily functions?
Is Pain Controlled by Genes?
The team focused on a human gene called SCN9A.
The gene is highly active in nerve cells outside the brain and spinal cord, in the peripheral nervous system.
Once it is disabled, the ability to perceive pain is turned off.
And when this is overexpressed, people become unusually sensitive to pain.
Generally speaking, gene expression is the process by which genetic information (DNA or RNA fragments) expresses itself as external traits by guiding the synthesis of living macromolecules (proteins, etc.).
The genes that control hair color, for example, can make our hair look different by controlling the proportion of eumelanin and melanin in our hair.
SCN9A is a gene that controls human’s ability to feel pain, and its expression level and way will largely determine a person’s ability to feel and tolerate pain.
Specifically, the pain gene acts on a special sodium channel in nerve cells (Nav1.7), which plays a role in transmitting pain information from peripheral nerves to the brain.
In other words, the pain gene does not act on the central nervous system itself, but only on the process by which the peripheral nerves transmit information to the central nervous system.
If there were a way to safely weaken the signaling of sodium channels, chronic pain might no longer be a problem.
The human ability to feel pain is controlled by genes, and it may be possible to modulate pain perception through gene therapy.
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“Simple” and “clean” pain genes
Rememingly, the pain gene acts almost exclusively on this sodium channel and has little effect on the body’s other physiological activities.
This is a very rare condition in humans.
Generally speaking, genes that control one trait may also control other traits, and a particular trait may be controlled by multiple genes at the same time.
But there is a simple one-to-one relationship between the pain gene and the sodium channel, which makes it easier to implement gene therapy.
One of the researchers involved in the study said: “One of the most exciting aspects of this treatment is that it uses a gene with a very simple and well-defined phenotype, and this gene is at the heart of the body’s pain response.
It’s the perfect target for people with chronic pain.”
The researchers used CRISPR/Cas-9, the newly popular gene-editing tool, and traditional zinc finger protein to edit the pain gene in mice. They also used a series of techniques to prevent the effects of the gene editing from being maintained permanently.
The mice in the study had chronic pain, including inflammatory pain and neuropathic pain.
In addition, they were subjected to a series of thermal or tactile stimuli.
The results showed that the gene therapy not only made the mice much more tolerant to short-term pain, but also maintained long-term relief from chronic pain.
In the mouse model of pain perception, the pain perception of mice and rats was judged by their appearance (0, no expression;
1, moderate;
2, severe.)
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The future is bright, but the road is tortuous
Of course, the technology is still in its very early stages, and there are countless questions that need to be answered before it can be used.
For one thing, mice, after all, are not representative, and they may still experience pain differently from humans.
Second, even if no side effects have been reported, this fact remains to be confirmed.
For example, abnormalities in the sense of smell have been reported in humans with a mutation in the pain gene SCN9A, but much research remains to be done on whether it is as “simple” as scientists once thought.
In addition, one of the basic senses the body uses to understand the world would have to be more cautious if turning off the gene not only alleviates pain but also deprives the body of the ability to feel it.
Here is a 71-year-old Scottish woman who has a mutated pain gene that means she has never known pain and therefore cannot act on it.
On her hands, we could see numerous burn marks.
A 71-year-old woman with a genetic mutation that prevents her from feeling pain has burns all over her hands.
| Source: [3]
For all these reasons, it can be concluded that gene therapy is difficult to be applied to actual pain treatment in the short term, but as a new route different from traditional therapy, it still deserves our attention and encouragement.
In the future, the team aims to test the efficacy of the treatment in larger animals and even laboratory primates.