Most people, if asked to contemplate a snakebite, would probably imagine a world of pain. But the venoms of snakes are very complex mixtures of chemicals, many of which have unexpected effects on the body. Now, researchers have dug through the contents of venom from the black mamba, and found it contains a potent painkiller, as effective as morphine, but lacking some of the side effects.

Black mambas in general have a fearsome reputation. They're one of the largest venomous snakes in the world, as well as one of the fastest moving. But their reputation is enhanced by their venom, which contains potent neuro- and cardio-toxins—ones that can cause paralysis and an irregular heartbeat.

Nevertheless, a group of French researchers included some black mamba venom in a screen they were doing. The goal was to find inhibitors of acid-sensing ion channels, proteins that appear on the surface of some nerve cells that are associated with the ability to sense pain from a variety of causes (not just acid). When triggered, these ASICs allow charged ions to enter nerve cells, starting a nerve impulse that can make its way to the brain.

The authors purified two small proteins (57 amino acids) that stuck to ASICs, which they termed mambalgins. They used the protein sequence to identify the genes that encodes them, and found they belong to a larger group of venom proteins called three-finger toxins. Most three-finger toxins kill the nerve cells they stick to, but that doesn't seem to be the case with mambalgins. In fact, animal testing revealed that the mambalgins "do not produce motor dysfunction, apathy, flaccid paralysis, convulsions or death upon central injections."

What they did do is quickly inhibit the ASICs expressed both in the brain and those found on sensory nerves in the periphery. That translated to a pain-killing ability that was roughly on par with morphine in some experiments. It also worked both when injected at the site of injury and when given systemically. That indicates it can block pain in sensory nerves and the relaying of pain signals by the central nervous system. The central nervous system effect appears to act independently of that pathway that mediates the effects of opioids.

In fact, the authors argue that the mambalgins reveal the presence of a previously unidentified pathway in the brain that relies on a specific combination of ASICs. It's impossible to ask a mouse about any side effects of being injected with these proteins, but the authors argue that the mambalgins are "powerful, naturally occurring, analgesic peptides of potential therapeutic value."

Nature, 2012. DOI: 10.1038/nature11494 (About DOIs).