SMALL AND MIGHTY

Scientists are turning to tiny venomous snails to create alternatives to opioid painkillers

The US opioid epidemic, which now kills 91 people per day, began with good intentions based on misinformation: Doctors in the mid-1990s started prescribing opioid painkillers more freely to help suffering patients after drug companies falsely advertised them as safe to use for chronic pain. In reality, though, drugs like Vicodin and OxyContin are highly addictive, and often lead patients to use heroin, a cheaper, illegal form of opiate that can be bought on the street. Any type of opioid can be lethal when taken in a high enough dose.

Now that health care providers are realizing the danger opioids cause patients, treating them for pain means accepting a trade off of risks: On the one hand, doctors don’t want their patients to endure any undue suffering due to an injury, surgery, or illness. On the other, they don’t want to prescribe drugs that could quickly become addictive and cause more harm later on.

To solve this problem, scientists are desperately trying to develop alternatives. They’re even taking tips from the animal kingdom: Research published (paywall) Feb. 20 suggests that tiny, venomous snails that live in Caribbean waters carry a compound that can alleviate pain in sick patients without using the addictive pathway opioids do.

Conus regius, or the crown snail, is a tiny critter that, at its largest, reaches just under 3 inches (7.5 cm). The snail’s venom, which it shoots into prey through microscopic hollow harpoons, makes up for its size: It quickly paralyzes the injection site, and then prevents the prey’s brain from sending signals to surrounding muscles. In one case, a 42-year-old man who was stung by a crown snail could barely move his arm for 12 hours (luckily, he made a full recovery).

Scientists from the University of Utah broke down the combination of toxins in the venom, and found that one compound, called RgIA4, works to block nerve pain—similar to the kind caused by cancer treatment and diabetes.

The research team then tested the compound on mouse models. They gave mice a chemotherapy drug known to cause nerve damage in humans that makes even routine sensations, like the feeling of clothing on skin, extremely painful. Then, some of these mice were treated with RgIA4. Somehow, the RgIA4 blocked the mice from feeling extreme sensitivity to cold—a common test used to measure nerve pain. Even though the compound itself stayed around in the mice’s bodies for only four hours, it had lasting effects. “[It] was still working 72 hours after the injection, still preventing pain,” J. Michael McIntosh, a psychiatrist at the University of Utah and one of the lead researchers on the project, said in a statement.

The team also used chemical modeling to show how RgIA4 could work in the human brain, and it appears that it binds with completely different receptors than opioids. Theoretically, this means that it wouldn’t be addictive, and, based on the duration of pain treatment in mice, could last much longer than traditional painkillers. They’ve still got a long way to go before RgIA4 can be tested in humans, but even finding this alternative pathway could help them come up with other novel, non-addictive drugs to treat nerve pain, if it turns out the snail venom isn’t quite the perfect solution.

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