Everyone has felt pain, and many experience it daily. But for such a universal sensation, it is still a mysterious one. We are only starting to understand the molecules that produce a painful sensation. Nature, however, is well ahead of us. Many animals are armed with chemicals that hijack the nervous systems of their targets, producing feelings of intense pain. They are unknowing neuroscientists, and by studying their weapons, we can better understand how pain manifests in our bodies.
Take the Texas coral snake. This brightly coloured serpent, clad in warning hues of red, black and yellow, usually shies away from confrontation. When it’s threatened, it defends itself with venom that can cause excruciating and unremitting pain.
Christopher Bohlen and Alexander Chesler from the University of California, San Francisco tested a wide variety of snake venoms for molecules that can trigger sensory neurons. The coral snake’s venom stood out. Bohlen and Chesler found that the active ingredient in this cocktail is a chemical called MitTx.
MitTx is a toxin of two halves, neither of which do anything alone. When they unite, the two subunits – MitTX-a and MitTx-b – activate proteins called acid-sensing ion channels, or ASICs. These act as gates that sit on the surface of neurons. When they detect an acidic environment, they open up and let ions into the cells, causing them to fire.
ASICs can be triggered by tissue injuries, inflammation or build-ups of lactic acid, and they tell our bodies that something is wrong. The coral snake hijacks this early warning system, by producing chemicals that turbo-charge it. Bohlen and Chesler found that when MitTx is around, acidic environments trigger a much stronger response from the ASICs. As a result, some sensory neurons fire over a thousand times more strongly than they normally would, and they take far longer to return to normal.
Other scientists have suggested that ASIC channels play a role in pain, but they have focused on a particular one called ASIC3, which is found on sensory neurons. However, the coral snake’s venom largely targets a different channel called ASIC1, which is found throughout the brain and in other parts of the body. Now that we have this lead, Bohlen and Chesler can take a deeper look at what ASIC1 does and how it contributes to normal painful sensations that aren’t caused by a snake-bite.
Bohlen and Chesler’s study shows just how informative venom can be in understanding how the body works. After all, these toxins work by corrupting the chemical reactions within a target’s body, so they tend to evolve from proteins that do fairly normal jobs. Natural selection acts like a shadowy organisation that turns workmen into assassins, and it recruits proteins with a certain profile.
Proteins are more likely to evolve into venom toxins if they’re secreted rather than fixed in place, if they’re involved in fast processes like neural firing or muscle twitching, and if they’ve changed very little over the course of evolution. These qualities mean that venom can work very quickly, and that an animal like a snake can affect a distant relative like a hungry dog).
All of this means that animal toxins are both diverse and constrained. There is a huge variety of them, but they often take on similar forms, so that venom genes can be startlingly similar in animals as distantly related as shrews and lizards, or playtpuses and snakes.
Indeed, the Brazilian coral snake – a close relative of the Texan one – also uses toxins that activate ASICs. The Trinidad chevron tarantula has a similar chemical weapon, but rather than making the channels respond more strongly, it locks them in an open state. The side effect of this, and it probably isn’t much relief, is that coral snake venom doesn’t work on anything that’s already been poisoned by a tarantula.
Reference: Bohlen, Chesler, Sharif-Naeini, Medzihradszky, Zhou, King, Sanchez, Burlingame, Basbaum & Julisu. 2011. A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain. Nature http://dx.doi.org/10.1038/nature10607
PS: I really wanted to call this post “How coral snakes elected the way of pain” but of course, animals don’t steer their own evolution.
Photo by National Natural Toxins Research Center at Texas A&M University-Kingsville
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