A snakebite may bring on a world of hurt, but a substance found in black mamba venom could actually relieve pain. The finding reveals a new possible approach for pain treatment, researchers report online October 3 in Nature.
The black mamba, Dendroaspis polylepis polylepis, is one of the most lethal snakes on Earth. But a team of researchers in France found that compounds in the snake’s venom have the same pain-banishing effect on mice that morphine does.
The compounds, called mambalgins, appear to work by blocking certain channels in nerve cells. Under acidic conditions, these channels open up, triggering pain signals. By preventing the flow of charged atoms through these channels, the mambalgins stop pain signals in their tracks.
The work highlights such acid-sensing channels as a potential target for pain treatment, says neuroscientist Candice Askwith of Ohio State University, who was not involved in the study. Morphine and other opioids work well, she says, “but they do have limitations and they do have side effects. So having an alternative chemical or pathway that could be manipulated would be a great advantage clinically.”
Molecules found in the venom of snakes, predatory sea snails and many other animals have been widely studied for their therapeutic effects in conditions ranging from diabetes to cardiovascular disease. The venom toxins home in on specific nerve channels, activating or deactivating them. While some snake venom compounds cause pain, the researchers noticed those in black mamba venom seem to do the reverse.
“If you inject the venom, it’s really deadly — you quickly kill the animal,” says study coauthor Eric Lingueglia of the Institute of Molecular and Cellular Pharmacology in Valbonne, France. “But surprisingly, if you inject a small constituent of the venom — the mambalgins — you have no neurotoxic effect and you have analgesia.”
Lingueglia’s team injected mice with either the venom ingredient (mambalgin) or morphine before exposing the animals to hot water or after injecting them with chemicals designed to cause painful inflammation. In most of the tests, the venom treatment soothed pain as well as morphine did. The mambalgin was effective when injected into either the central nervous system — comprising the brain and spinal cord — or the peripheral nervous system. And because mambalgin appears to work through a different mechanism than morphine, it lacks some of the side effects that plague morphine use, such as breathing problems and increasing tolerance to the drug.
Although the researchers suspected mambalgin was targeting a particular type of acid-sensing nerve channel, they needed proof. There are two possible explanations for the mambalgin’s effectiveness, says Lingueglia: “The optimistic one is that the analgesic effect is due to inhibition of the targets you have identified, and the pessimistic one is that your analgesic effect is due to inhibition of another target you don’t know about.”
In mice lacking a functional gene for the suspected nerve channel, the venom compound had no hurt-reducing effect, confirming that these channels are indeed crucial players in its pain-placating mechanism.
While the snake venom painkiller worked like a charm in mice, its effectiveness in humans has yet to be shown. Although the research focused on only one type of pain — acute inflammatory pain — Lingueglia says future studies will explore its effect on other types, such as neuropathic pain, which can be very difficult to treat.
“We are just at the beginning of the story,” says Lingueglia, but “the pain pathways are pretty well comparable in mice and humans, so we expect that this will also be effective in humans.”
S. Diochot et al. Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature. Published online October 3, 2012. Doi:10.1038/nature11494. [Go to]
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