How puffer fish can help treat pain in cancer patients

The Conversation

What if I told you that pufferfish could help us combat the pain associated with cancer? This animal is a fascinating being and not only for its aesthetics and morphology, which has made it the protagonist of films, but also for its medicinal properties associated with a substance it produces: tetrodotoxin.

A trip through Asia in search of puffer fish

First, we will embark on a trip through the Asian continent, where we will have the opportunity to eat its meat, considered a delicacy. But be careful! Our lives could be at risk. Pufferfish produce a potentially fatal toxin, tetrodotoxin. In fact, A few milligrams would be enough to kill him.

So… how do we eat this? For centuries, Asians have developed specific culinary techniques to inactivate the toxin so that it can be enjoyed safely. In a modest restaurant in the Haedomari market, in the coastal town of Shimonoseki (Japan), chef Saito Hamada shows us how he detoxifies the body. fugu –as they call it there– using the technique migaki.

The puffer fish has medicinal properties associated with a substance it produces: tetrodotoxin.Hal Beral/Getty Images

Despite the extensive popular experience in consuming this fish and the knowledge of the poison it produces, there are hundreds of poisonings annually associated with tetrodotoxin. Hamada warns us to only consume meat from fugu in certified establishments that guarantee proper processing. In fact, to be able to cook it legally, a license obtained after several years of training is required.

After tasting puffer fish in all its culinary forms, we return to Europe where, curiously, there have also been cases of poisoning.

Good news from Granada

To expand our knowledge about the therapeutic applications of tetrodotoxin, we will now travel to Spain. On the top floor of the Faculty of Medicine of the University of Granada, one of the tallest buildings in the city, we met José M. Baeyens and Francisco R. Nieto, professors of the Department of Pharmacology.

In their office, with Sierra Nevada in the background, they tell us that they have been investigating the possible usefulness of tetrodotoxin as an analgesic in a model of neuropathic pain (that which occurs when there is damage to the nervous system) induced by chemotherapy in animals. experimentation (preclinical trials), obtaining very promising results.

In fact, a few years ago they participated in the patent of said molecule for the treatment of neuropathic pain induced by antineoplastic chemotherapy (which prevents cell proliferation).

Today, the efficacy of tetrodotoxin in preclinical models of neuropathic pain is very solid and has been confirmed by numerous groups from different corners of the world. Regarding its clinical evidence, focused on cancer-related pain, it is more modest but robust, as confirmed by several phase II and III clinical trials.

Cancer pain and its treatment with tetrodotoxin

Cancer-related pain is a complex, heterogeneous and very common phenomenon. It may be due to the tumor growth itself or its treatment with surgery, radiotherapy or chemotherapy. It usually has a high neuropathic component, which makes its treatment difficult to manage.

In particular, neuropathy induced by cancer chemotherapy is a real headache for patients and doctors. Few drugs work and none are specific for this problem, since most are antidepressants or antiepileptics that have shown moderate effectiveness and produce numerous undesirable effects.

In this context, there is a need for new analgesics to treat cancer-related pain. And this is where tetrodotoxin comes into play, whose clinical development is in an advanced stage. In fact, a recent meta-analysis in which I participated concluded that it is effective in treating cancer-related pain without increasing serious adverse effects.

“Its clinical usefulness is exciting: it has shown effectiveness in a type of pain that is especially difficult to treat, peripheral neuropathy associated with chemotherapy,” comments Professor Nieto. For his part, Professor Baeyens adds: “There are also clinical trials that show effectiveness in patients with cancer-related pain, a more heterogeneous condition with a very high prevalence.”

Anyway, these Clinical results are preliminary and must be confirmed with trials involving a larger number of patients.

A phase III clinical trial is currently underway to justify the marketing request and we will soon know the results. If approved by regulatory agencies, it would be the first drug developed specifically for peripheral neuropathy associated with chemotherapy and a great joy for so many patients who would see their lives drastically improved.

One more example that nature is surprising and that almost everything in life can have a solution, even the most complex pain. And thanks to these investigations, we are getting closer to eliminating it.