Researchers have taken an interest in a euphorbia plant growing in Marocco as a possible painkiller. The plant’s active ingredient, resiniferatoxin (RTX), is extremely spicy, a 10,000 times hotter than the world’s hottest pepper. RTX is a potent analog of capsaicin, the active ingredient in chilli peppers, and has numerous benefits over existing painkillers. It doesn’t require frequent dosing, targets only the areas causing pain, and doesn’t produce a potentially addictive high. All this makes it a promising candidate for the clinics.

On the Scoville Scale of hotness, RTX reaches 16 billion units. That is 10,000 times hotter than the Carolina Reaper and 4.5 million times hotter than a jalapeno chili pepper. Euphorbia resinifera, so-called resin spurge, is definitely not to be eaten.

The human body has different kinds of sensory neurons. Some flavors respond to touch, others signal limb position, yet others respond only to stimuli like injury and frost. RTX binds to a TRPV1 (pronounced TRIP-vee one) molecule in specifically pain-sensing nerve endings. TRPV1 receptor responds to temperature, but it also responds to a family of molecules called pungents. They include capsaicin, the active ingredient in hot pepper.

“So when you put hot pepper on your tongue and it feels like it’s burning, it’s not because your tongue is on fire,” Tony Yaksh, an anesthesiologist and pharmacologist at UC San Diego who’s studied RTX, said for WIRED. “It’s simply activating the same sensory axons that would have been activated if your tongue had been on fire.”

RTX is a capsaicin analog and up to 1000 times more potent. When injected into the body RTX binds to TRPV1. This opens an ion channel in the nerve ending that allow calcium to flow through. This calcium overload deactivates the pain-sensing nerve endings.

RTX is highly specific to TRPV1. “So you gain selectivity because it only acts on TRPV1, which is only on a certain class of fibers, which only transmit pain,” said Yaksh. “Therefore you can selectively knock out pain without knocking out, say, light touch or your ability to walk.”

If researchers want to treat knee pain, they will inject RTX directly into the knee tissue. Patients need to be anesthetized first since the pain would be too intense otherwise. After a few hours, that knee is desensitized to pain. It is not just a theory anymore. Researchers have already made tests on dogs and results are promising.

“It is profoundly effective there, and lasts much, much longer than I might have expected, maybe a median of 5 months before the owners of the dogs asked for reinjection,” said Michael Iadarola, who’s studying RTX at the National Institutes of Health (NIH). “The animals went from basically limping to running around.” One dog even went 18 months before the pain had returned.

RTX is a very good solution for targeted applications, but it can also work as a powerful painkiller for widespread pain. The NIH is already in the midst of trials with bone cancer patients.

“We use the same technique for administering this as we would a spinal anesthetic,” said NIH anesthesiologist Andrew Mannes. “The whole idea is you’re not injecting into the spinal column itself, you’re injecting it into the fluid that surrounds the spinal column.”

This way damage to the cord is avoided. For the process, patients are anesthetized and afterward treated with short-term painkillers. Over the next few hours the pain subsides until the point where patients don’t feel the pain any longer. Because RTX is injected more centrally, it delivers widespread pain relief.

“For many of the cancer patients, we need to have the drug remove pain from a lot of different regions,” said Michael Iadarola. “So we give it into a compartment where the nerves to the lower half of the body are gathered together.”

Evolutionary, we feel pain for a good reason. Pain lets us know we are doing something to our body that we should not be. Like drinking ice cold water or shaving with an old razor. So, is it a problem if painkillers get too effective? For people with localized pain, not really. Since injections target a specific area, the rest of the body can still feel pain. Moreover, for those in terminal conditions a central injection can bring long-awaited relief.

“We’re doing that on cancer pain patients who have tried all other treatments and they’ve not been successful,” said NIH neurosurgeon John Heiss. “The FDA has only allowed us to have the indication for cancer patients with limited life expectancy because the concern is that if you lose pain and temperature sensation you could have deleterious effects.”

RTX’s advantage lies in its specificity. Broadly used opioids target receptors all over the body and not only a specific kind of sensory neuron. Consequently, patients could get problems with constipation, sedation or engage in respiratory depression. That is not the case with RTX.

Another of RTX’s advantages is that patients do not have to take it constantly. “You give it once and it should last for an extended period of time because it is destroying the fibers,” said Mannes. “But the other thing with this to remember is there’s no reinforcement. There’s no high associated with it, there’s no addiction potential whatsoever.”

If RTX does become widely available for human use, it will probably be used to only treat serious conditions. By more directly addressing the root of the pain, it could help us cut back on opioids and other painkillers with wide impact and addiction issues.

You or someone you know struggling with addiction? The experts at can help out!

Learn more about resiniferatoxin in the video below:

By Andreja Gregoric, MSc