[New research] Discovery of the chronic pain treatment process!

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Author: Yun Introduction: Recently, a new version of CRISPR gene therapy can temporarily inhibit the Nav1.
7 gene (a gene related to perception of pain) and increase mice Pain tolerance reduces their sensitivity to pain and provides months of pain relief without causing numbness
.

For pain, people have been looking for ways to explain the source and eliminate the pain for thousands of years
.

Although we have a better understanding of the mechanism behind this feeling, we are still puzzled by many issues and continue to look for better pain relief methods
.

Hundreds of years ago, the ancient Egyptians used a decoction of dried leaves of the Myrtle family plant on the back and abdomen to relieve uterine pain; then, the Greeks used its aspen bark/willow bark extract to treat eye diseases; chewing Willow bark extract relieves childbirth pain and fever
.

In 1899, Hoffmann, a chemist from Bayer, Germany, successfully synthesized aspirin, which has anti-inflammatory, antipyretic and analgesic effects
.

So far, aspirin has been used for a hundred years and has become one of the three classic drugs in the history of medicine.
It is still the most widely used antipyretic, analgesic and anti-inflammatory drug in the world
.

On March 10, 2021, the University of California, San Diego published a study titled "Long-lasting analgesia via targeted in situ repression of NaV1.
7 in mice" in "Science Translational Medicine"
.

This is a new version of CRISPR gene therapy, which works by temporarily inhibiting the Nav1.
7 gene (a gene related to pain perception), increasing the tolerance of mice to pain and reducing their sensitivity to pain.
It also provides months of pain relief without causing numbness
.

In fact, chronic pain itself is already a high-incidence disease
.

According to epidemiological survey data, the overall prevalence of chronic pain remains high worldwide, 17.
5% in Japan, 37.
6% in South Korea, 19.
9% ​​in Thailand, 21% in Morocco, and 24.
9% in Germany
.

In China, there are more than 300 million people suffering from chronic pain, and it is increasing at a rate of 20 million every year
.

When chronic pain occurs, the painful parts often involve multiple areas and are difficult to relieve.
The patients are often accompanied by sleep disorders, depression, and anxiety
.

Due to the serious impact on the quality of life and physical and mental health of patients, some people compare chronic pain to an immortal cancer
.

At present, analgesic drugs are widely used, mainly to relieve all kinds of pain and relieve the patients' emotions such as fear and nervousness
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The most common analgesic drug is morphine.
In fact, the analgesic effect of morphine is very good.
Morphine can directly act on the nerves of the human body.
Through various links, it can increase the anti-pain system in the human brain and reduce the body’s internal and external environment.
Sensitivity to stimulation can achieve very good analgesic effects, but long-term medication will form a certain degree of drug resistance
.

Morphine is mainly targeted at patients with advanced cancer
.

Morphine is not recommended for mild pain
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There are many factors that cause chronic pain, and its treatment methods are also more complicated
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At present, the main method of treating chronic pain is opioids
.

However, opioids are specially managed narcotic and psychotropic drugs that have potential risks such as safety, compliance, drug dependence, and abuse/addiction.
Long-term use of opioids may lead to poor prognosis
.

In fact, there are many painkillers.
Most painkillers have certain side effects.
It is not recommended to use them in large quantities, so you should not abuse painkillers
.

CRISPR Therapy to Suppress Pain Genes Traditional CRISPR gene therapy can treat diseases by editing a person's genome, but the technology that permanently changes the genetic code is not suitable for pain relief
.

Because the moderate pain signal can remind the patient to pay attention to it and prevent the body from getting more harm
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When patients have a long life expectancy, it is not a good thing to permanently eliminate their pain perception ability
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"You don't want to lose the ability to sense pain forever," Moreno said
.

"One of the biggest concerns of CRISPR gene editing is the off-target effect
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Once you cut the DNA, it's over.
.
.
We will not do irreversible things
.

" The new version of CRISPR is different from the previous direct editing of target genes.
Instead, it prevents gene expression and does not cause permanent changes to the gene
.

In other words, they do not completely eliminate pain, but by inhibiting the Nav1.
7 gene of individuals with chronic pain, reducing the gene expression and bringing it to a non-pathogenic level
.

The researchers explored two independent genetic methods to inhibit the spread of pain at the spine level.
One is to use the dCas9 protein (which does not produce cutting, only adheres to a genetic target and prevents its expression) to achieve NaV1.
7 non-permanent gene suppression; the other is the use of ZFP zinc finger protein (recognizing and modifying specific DNA sequences) for epigenetic regulation of the expression of NaV1.
7
.

The two proteins are packaged in adeno-associated virus (AAV) and shuttle into the cell
.

Both methods worked! A schematic diagram of the genetics of inhibiting chronic pain in mice.
They injected mice with inflammation and chemotherapy-induced pain to the spinal cord.
These mice showed a higher pain threshold than mice that did not receive gene therapy: they were stimulated by pain (heat , Cold or pressure), the paw retracts more slowly, and it takes less time to lick the paw after being injured
.

Through controlled experiments with three different models, the research team concluded that the in situ inhibition of NaV1.
7 can achieve long-term analgesia
.

The treated mice showed a higher pain threshold than the control mice.
Since the Nav1.
7 gene is only related to pain, the mice did not lose any sensation except for pain, nor did they show any changes in normal motor function, which means This treatment plan has no other side effects
.

Gene therapy of Nav1.
7 gene can relieve chronic pain without causing side effects, although these results are still in the preliminary stage, and more work needs to be done in order to be translated into humans
.

With the discovery of this CRISPR therapy that inhibits pain genes, humans have one more method for the treatment of pain, and compared with commonly used drugs for pain relief, it has no side effects.
This is another milestone in the study of chronic pain treatment methods.
Found out
.

Reference materials: https://stm.
sciencemag.
org/content/13/584/eaay9056.
full Note: This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment options
.

If you need health guidance, please go to a regular hospital
.