“This Chemical Is So Hot It Destroys Nerve Endings—In a Good Way: Resiniferatoxin Is 10,000× Hotter Than the Hottest Pepper, and Has Features That Make It Promising As a Painkiller of Last Resort”, 2018-11-14 (; backlinks):
In Morocco there grows a cactus-like plant that’s so hot, I have to insist that the next few sentences aren’t hyperbole. On the Scoville Scale of hotness, its active ingredient, resiniferatoxin, clocks in at 16 billion units. That’s 10,000× hotter than the Carolina reaper, the world’s hottest pepper, and 45,000× hotter than the hottest of habaneros, and 4.5 million times hotter than a piddling little jalapeno. Euphorbia resinifera, aka the resin spurge, is not to be eaten. Just to be safe, you probably shouldn’t even look at it.
But while that toxicity will lay up any mammal dumb enough to chew on the resin spurge, resiniferatoxin has also emerged as a promising painkiller. Inject RTX, as it’s known, into an aching joint, and it’ll actually destroy the nerve endings that signal pain. Which means medicine could soon get a new tool to help free us from the grasp of opioids.
…RTX is a capsaicin analog, only it’s 500–1,000× more potent. When RTX binds to TRPV1, it props open the nerve cell’s ion channel, letting a whole lot of calcium in. That’s toxic, leading to the inactivation of the pain-sensing nerve endings.
This leaves other varieties of sensory neurons unaffected, because 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”, says Yaksh. “Therefore you can selectively knock out pain without knocking out, say, light touch or your ability to walk.” So if you wanted to treat knee pain, you could directly inject RTX into the knee tissue. You’d anesthetize the patient first, of course, since the resulting pain would be intense. But after a few hours, that pain wears off, and you end up with a knee that’s desensitized to pain.
Researchers have already done this with dogs. “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”, says Michael Iadarola, who’s studying RTX at the National Institutes of Health. “The animals went from basically limping to running around.” One dog even went 18 months before its owners noticed the pain had returned…That and you have to take opioids constantly, but not so with RTX. “You give it once and it should last for an extended period of time because it is destroying the fibers”, says 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.”