Black mamba snakes are among the deadliest serpents on Earth, but their venom contains compounds that might help people overcome pain.
For the first time, scientists have isolated compounds called mambalgins from black mamba venom and injected them into mice. The venom ingredients worked as well as morphine at dulling pain in the rodents, but with fewer side effects and no toxic consequences.
The compounds appear to work by blocking structures in the nervous system called ion channels. People have these kinds of structures, too.
"These channels become therefore new potential therapeutic targets against pain," said Anne Baron, a molecular physiologist at the Institute of Molecular and Cellular Pharmacology in Valbonne, France. "It is remarkable that all of this was made possible from the deadly venom of one of the most venomous snakes."
Chronic pain affects some 20 percent of adults and half of all elderly people, Baron said. But many of today's painkillers cause side effects or lead to addiction, and many come with long-term safety concerns.
In the search for better drugs, some researchers have turned to the venoms of snakes, scorpions, spiders, cone snails and other creatures. Over millions of years of evolution, these animals have developed molecules with powerful effects on the nervous systems and cardiovascular systems of their victims.
Baron and colleagues have been particularly interested in structures called ASIC channels, which carry charged sodium atoms or ions across the membranes of nerve cells and have been implicated in causing pain in rodents, humans and other animals.
Previous research has shown that these ion channels appear in several parts of the pain pathway, including in the neurons that sense pain and in the spinal cord, where they send information to the brain. When the channels are open, electrical signals pass through.
Because some snake venoms are known to contain compounds that act on ion channels, Baron's team decided to screen black mamba venom for possibilities.
When the researchers discovered that the venom could block the electric currents flowing through ASIC channels, they purified the small protein compounds -- called peptides -- responsible for the effect. These mambalgins made up less than half a percent of the venom's proteins.
Finally, the team injected the mambalgins into mice before subjecting the rodents to various kinds of pain, including the immersion of a paw in water heated to 115 degrees Fahrenheit. Armed with venom compounds, the mice were slower to withdraw their paws from the water, the researchers report today in the journal Nature. That means they felt less pain.
It will take years of further research to turn the finding into new kinds of painkillers for people.
For now, the discovery helps illuminate some of the ways that pain works and what role ion channels play in causing pain, said David Julius, a neuroscientist at the University of California, San Francisco. In his own work, he and colleagues have found that pain-inducing toxic compounds in the Texas coral snake activate the same channels that the black mamba compounds inhibit.
The new study also highlights the broad potential of venom to inspire advances in medical research.
"Each of these venoms contain dozens if not hundreds of different peptides or small molecules, and we've only likely tapped a small component of that," Julius said. "There's a really great pharmacopeia of things in there and a wealth of potential tools and insights we can get from them. I'd say the potential is huge."
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