Paolo Rossi Castelli 29 December 2021 5 min read

A new pain-relief strategy from Arizona

A molecule (currently known as 194) has been identified that seems to be as powerful as opiates, but without the negative effects and, in particular, it appears non-addictive.

Researchers at the University of Arizona in the US have made an important breakthrough in pain relief, by identifying a substance from among 50,000 possibilities that can block feelings of pain as effectively as opioids, but without causing dependency.

So how did they do it?
It all starts, explains the journal Science Translational Medicine - with an in-depth knowledge of mechanisms that control how we perceive pain: in particular, the sodium ion channels (to give them their technical name). These are minute channels that open onto the surface of nerve cells in response to changes in electrical potential, to allow the movement of ions like calcium, potassium, chloride and sodium in two directions – into and out of the cell. These ions have their own positive or negative electrical charge and are electrically 'unbalanced' atoms. As ions flow through the channels they alter the cell’s electrical state, triggering the reactions that usually take place inside it and controlling the transmission of nervous impulses.

It has long been thought that altering the activity of these channels could ‘turn off’ pain stimuli. Until now, however, attempts to block the most important of these channels in terms of producing pain, known as NaV1.7, have been unsuccessful. Researchers at the University of Arizona decided to stop looking for a direct inhibitor, and to try instead to act on NaV1.7 by altering its activity indirectly with a compound called 194, chosen as stated above from 50,000 candidate substances. By acting on certain proteins and enzymes, this keeps NaV1.7 closed and stimulates the system of endogenous opiates (those produced by the body itself, like endorphins).

An aid to recovery
194 proved highly effective in laboratory experiments on different cell ‘pathways’ and this was also the case when it was tested on six different types of animals. There were no significant side effects, or any dependency or tolerance. 194 also acts in synergy with classic opiates like morphine and could be an important aid in getting clean and alleviating addiction.

Opioid abuse causes alarm in the U.S.
50-60,000 people die of opioid overdoses in the U.S. alone each year. The situation is so serious that Congress has officially declared it a health emergency. It is estimated that almost one in three people suffer from chronic pain and are prescribed opioids for conditions like back pain that could be treated in other ways. One in three users do not take opioids correctly and one in ten quickly become addicted to them. This is why alternatives are so urgently sought.

Studies will continue on 194 with a view to testing on humans as soon as possible.

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Paolo Rossi Castelli

Journalist since 1983, Paolo has been dealing with scientific divulgation for years, especially in the fields of medicine and biology. He is the creator of Sportello Cancro, the site created by corriere.it on oncology in collaboration with the Umberto Veronesi Foundation. He collaborated with the pages of the Science of Corriere della Sera for several years. He is the founder and director of PRC-Comunicare la scienza.