Chronic pain affecting mental and physical health can be treated with this new method, research finds-health

The effects of chronic pain include physical and mental health damage, decreased productivity, and drug addiction. A new study, led by scientists at the Weizmann Institute of Science, uniquely treats this pain by targeting a major gateway that leads to activation of genes in peripheral nerve cells that play a role in many forms of chronic pain. Suggests an approach.

The results of this study were published today in Science.

Pain begins with sensory neurons-sensory neurons pass information from the skin to the central nervous system. Damage, chronic damage, or illness to these neurons can “short-circuit” them and send a continuous pain message.

Professor Mike Fines Gilber of the Institute of Biomolecular Sciences is investigating the molecules that regulate biomolecular messaging activity within these neurons. Found in all cells, these molecules-importins- act as conduits between the cell nucleus and its cytoplasm, allowing molecules to enter and exit the nucleus and control access to genes.

This role is of special importance in peripheral nerve cells, a long, thin body that can take several hours for molecular messages to reach the nucleus from nerve endings. Several key Fein Gimbers and his team, for example, relayed messages about damage to nerve cell bodies and initiated repair mechanisms.

To ask if Infantin is involved in chronic neuropathic pain, a researcher led by Dr Letizia Marvaldi of Fainzilber’s group was first generated by the lab of Dr. Michael Bader of Professor Max-Delbruck. We have set out to screen a large number of importin mutant mouse strains in the center of Berlin in collaboration with this study. The research was supported by the European Research Council.

Behavioral screening of these different lines revealed a specific importin-importin alpha-3-3 as the only importin involved in the control of pain pathways. Next, the team identified a gene expression pattern associated with persistent pain in peripheral nerve cells and examined how it was associated with importin α-3 activity.

Analyzing the difference in expression patterns between normal and importin-alpha3 deficient neurons, Malvardi turned his attention to c-Fos, a protein that importin-alpha3 brings to the nucleus. c-Fos is a transcription factor-a molecule that increases or decreases the expression of many genes. Further experiments in mice have shown that c-Fos accumulates in the nucleus of peripheral nerve cells in mice suffering from chronic pain.

Next, we used a specialized virus as a tool to reduce or abolish mouse peripheral nerve importin α-3 or c-Fos. These mice had significantly less response to chronic pain situations than did normal mice. Further studies have shown that importin alpha-3 is important for late and chronic pain. c-Fos is also involved in the early pain response, but seems to enter the nucleus by other means in the early stages. This suggests that blocking importin α-3 activity is particularly suitable for preventing persistent chronic pain.

The research team then took the discovery to the next level and asked how easy it could be to turn it into a clinical application. They used a special database called Connectivity Map (CMap) provided by Broad Institute of Massachusetts. This reveals a link between drugs and gene expression patterns.

This database allowed us to identify approximately 30 existing drugs that could target the importin α-3-c-Fos pathway. Nearly two-thirds of the compounds they identified were previously unknown to be associated with analgesia. The team chose two-one to test them again with cardiotonics and another with antibiotics-mice. In fact, injection of these compounds alleviates neuropathic pain symptoms in mice.

“The compound identified in this database search is a sort of fast track. It proves that drugs already approved for other uses in patients can probably be diverted to treat chronic pain,” Marvaldi said. States. “These compounds have already been shown to be safe in humans and may be in clinical trials in the near future.”

“We are now in a position to screen new and better drug molecules that can accurately target this series of sensory neuron events. Such target molecules are better than current therapies. It has fewer side effects, may be less addictive, and may offer new options to reduce the burden of chronic pain,” FineSilver said.

(This article has been published from the telegraph agency feed with no changes to the text. Only the headings have changed.)

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