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How coral snakes cause excruciating pain

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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4 thoughts on “How coral snakes cause excruciating pain

  1. What excites me most about this paper is that the authors find that the toxin activates the acid sensing ion channels by 2 or 3 orders of magnitude more than is observed when they are studied in a non-toxic setting. As activation potential is unlikely to be maintained unless it is useful this hints at ‘more potent physiological modulators for this class of excitatory channels’. I wonder what other system- beyond the ability to detect changes in Ph – these ion channels are involved in and if it is linked to an even stronger physiological response…

  2. This was fascinating to me. Enough so that I started checking into the citations in the Nature paper. In that paper the authors state “Venom from the Texas coral snake (Micrurus tener tener), whose bite produces intense and unremitting pain9, excites a large cohort of sensory neurons”. So I checked citation 9: Morgan, D. L., Borys, D. J., Stanford, R., Kjar, D. & Tobleman, W. Texas coral snake (Micrurus tener) bites. South. Med. J. 100, 152–156 (2007) . This was an interesting review of all the Texas Coral Snake bites that they authors could find between 2000 and 2004. What interested me the most is that Texas Coral Snake bites are not very dangerous at all and in fact are usually mild even when antivenon is not delivered (however Eastern Coral Snakes are more dangerous). Apparently their reputation vastly overstates their macho death dealing ability. I thought that was pretty cool. Here are the conclusions of the paper:

    Poison Center data of 82 patients with bites from Texas coral snakes were analyzed and revealed that most were men, age 18 to 49 years old, bitten on a finger. A skin disruption at the bite site was noted for over 80%, and almost 90% had local swelling, pain, erythema, or paresthesia. Only 7.3% had systemic effects, and none of these were severe. Over half received coral snake antivenin, and 15.9% were given opioids for pain. No patient died and no patient required mechanical ventilation due to hypoventilation from the snakebite. This review of Texas coral snakebites found more severe local findings, and less severe systemic effects than previously reported. Antivenin is not needed for most of these patients, and opioids may be given safely.

    The main point I want to make though, is that this paper does not seem to suport the statement that it was cited for: “Texas coral snake…bite produces intense and unremitting pain”. This is what the Morgan et al. say about pain:

    Seventy (85.4%, 95% CI: 76.1–91.4%) of the 82 patients had some abnormal finding at the bite site. Thirty-eight patients (46.3%, 95% CI: 36.0–57.1%) noted localized swelling, and 3 (3.7%) had significant swelling. Thirty-five (42.7%, 95% CI: 32.5–53.5%) patients reported some pain, and 13 (15.9%) reported more than mild pain that required multiple doses of medication. This pain frequently radiated up the arm or to the chest. Twenty-four patients (29.3%) were noted to have both pain and swelling, and two patients (2.4%) had both significant pain and significant swelling. Other local findings were erythema, paresthesia, numbness, and a small area of ecchymosis

    So only 35% of patients reported any pain only 16% had pain that was severe enough to actually warrant serious analgesics. Morgan et al also note that “Previous studies report minor swelling and no pain.5,10”. They also mention that two cases (of the 37 that did not receive antivenin) had “severe pain”. There is no description in the paper that sounds quite like “intense and unremitting”. Now perhaps that sort of pain does occur, but I don’t see how the authors of the Nature paper know that to be the case. This does not of couse invalidate their findings but it is irritating that they seem to have over dramatized the background information.

  3. Seconding Matt K.’s message above, quite a lot of on-line sources say that coral-snake bites are not particularly painful. I also read that coral snakes frequently “dry bite” – strike without injecting venom. (One source said as many as 50% of coral snake vs. human incidents are dry bites.) I’m speculating, but I wonder whether the unusually high percentage of dry bites for coral snake strikes might be at least part of the explanation for the sharply contradictory claims about coral snakes being unusually painful or unusually painless.

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