Pain is a defensive mechanism that is activated in the face of potentially harmful stimuli, but not all are able to feel it. Certain mutations make some people suffer from congenital insensitivity to pain. Most do not reach adulthood, since over the years they can suffer fractures, serious burns or conditions such as appendicitis or infarctions without noticing it.
Specifically, these individuals are born without proteins that belong to the family of the so -called “Voltage dependent sodium channels” or Christmas.
Christmas proteins work as doors: when they are closed, pain neurons are at rest, but when they open – for example, when we touch something that may burn us – let positive sodium ions and those nerve cells, called nociceptors, pass into the interior, are activated. Thus we feel pain and, most importantly, we activate a protective response of withdrawal.
Now, those same sodium channels responsible for our survival have shown to have a key role as therapeutic target against pain: after more than 20 years of research, a new molecule has been approved that acts by blocking them: the Suzetrigine (Journavx, by its commercial name). In clinical trials, he has revealed a great analgesic power.
Proper Christmas
Our NAV, present in each and every one of our cells, differ slightly from each other according to what tissue they are in. For example, in the heart we have those of type 1.5, fundamental for the adequate contraction of the myocardium, while in the neurons that feel the pain work nav 1.7, 1.8 and 1.9. In experimental models, If the opening of the latter is blocked with drugs or genetic manipulations, an analgesic effect occurs.
The “specific pain” Christmas has been known since the beginning of the 21st century. So why has it taken so long to develop suzectrigine?
The answer is not simple, since various factors intervene. The process of developing a drug is long and, at least, it usually lasts about 10 years. After showing efficacy and animal safety, 3 phases of clinical trials in humans must pass, with many possibilities that do not reach the end. In the case of analgesics, the success percentage is even lower.
With the compound that concerns us, the problem was that NAV subtypes are very structurally similar. And design a drug that interacts specifically with the Nav of interest (in this case the NAV1.7, 1.8 or 1.9) without doing so with any other (for example, the Nav1.5 of the heart) is extremely complex.
This “nonspecific” mechanism on all NAVs have it, for example, local anesthetics, such as those that the dentist puts us. It is true that thanks to them we stop feeling pain, but they also abandon us the necessary sensations to “move” correctly. Who has not ever left the dentist with his mouth asleep and practically unable to speak?
The use of these drugs should always be located in an area (where it is injected), since if they are administered in blood and reach other organs such as the heart we would have a problem. In fact, under strict monitoring, they are also used for the treatment of certain arrhythmias.
Nature gives us some solutions, and the scientists who study pain know how to take advantage of them. For example, the tetrodotoxin or TTX It is a toxin produced by the balloon fish whose controlled use at very small doses is close to being approved for Treat the pain associated with cancer. We know that TTX selectively inhibits the subtypes of the ships of the roads that transmit the pain, although at high doses it loses that selectivity and is deadly.
After years of research, they could develop Highly selective molecules for NAV1.7 and NAV1.8 which showed very promising preclinical results in animal studies. Clinical trials for NAV1.7 inhibitors were negativebut a selective molecule that blocks NAV1.8 (the antagonist VX-548, now called Suzetrigin) has turned out quite effective and safe as analgesic.
A milestone in a moment of necessity
This is a milestone after 20 years of notable failures in large clinical trials such as nervous growth factor inhibitors or angiotensin ii type 2 receptor antagonistswhich caused millionaire losses.
Inflammatory pain is usually treated with non -steroidal anti -inflammatories such as ibuprofen or minor analgesics such as paracetamol. However, when the pain is very severe, opioid drugs must be resorted to, which entails side effects that limit its use.
The main adverse effect of opioids, addiction (tolerance and dependence), in combination with a marketing misleading and overpred Thousands of overdose deaths. On the other hand, for other types of pain such as neuropathic (which is produced by damage or dysfunction of the peripheral or central nervous system), There are not even clearly effective analgesics.
For all the above, specialists in pain treatment have received the approval of Suzetrigin as a ray of hope. In addition, the mechanism of action of this new drug is completely different from any of the medications used so far: it not only touches the somatosensory route responsible for transmitting the pain, but it does so in the same neuron that detects it.
This medicine is expected to be used alone or in combination with non -steroidal anti -inflammatories, but it is also proposed that they replace, at least partially, opioids in the treatment of chronic pain.
Although its approved indication is for the management of acute post -surgical pain, they are currently being carried out several clinical trials to evaluate its effectiveness in the treatment of neuropathic pain, whose current approach remains limited.
At the moment, it remains to wait to see how this medicine behaves in real life, with more heterogeneous populations and outside a controlled environment. If you meet efficacy expectations and do not appear for security problems, we will be faced with one of the most used and worldwide medications.
Pain researchers will closely follow the results of clinical trials for neuropathic pain, since the approval of this indication could be supported, where new therapies are urgently needed.
Miguel Ángel Huerta Martínez is a predoctoral researcher at the University of Granada / Carolina Roza is a professor and researcher at UNIR
This article was originally published in The conversation. You can read it here
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