A Texas coral snake (Micrurus tener) showing its characteristic red-yellow-black banding pattern. While generally shy and non-confrontational, the snake's neurotoxic venom can produce extreme pain, and even death.
Credit: National Natural Toxins Research Centre at Texas A&M University-Kingsville
LONDON: Exactly how venom from snakes is capable of causing such strong and lasting pain has been identified by a group of scientists in the U.S.
Research into natural, pain-inducing toxins can be useful for investigating how pain occurs in the body at a molecular level, through the sensory neurons and receptors. Whilst pain is a common occurrence in humans, much of what causes it is still a mystery. A new study published in Nature today aims to change that.
According to co-author Baldomero Olivera from the University of Utah, research into a small, venomous species of North American snake called the Texas coral snake has revealed which particular sensory paths in the body are used to transmit pain. "Natural products that elicit discomfort or pain represent invaluable tools for probing molecular mechanisms underlying pain sensation," the researchers said.
Investigating venom
For years, natural products that cause pain or discomfort in humans and other animals have come under scrutiny from scientists investigating the causes of pain. But until now, research has focussed mainly on plant-derived irritants.
By going one step further and including snake venom in the study of pain, the team has uncovered evidence that more paths than previously thought can be used to cause and spread pain.
Led by David Julius from the University of California in San Francisco, the researchers first had to find a snake that had a venom capable of activating the right neurons. They screened the venoms from numerous snakes, and selected the Texas coral snake (Micrurus tener) because its venom activates a large group of sensory neurons and causes extreme pain. They then identified the active agents in the venom, naming them MitTx-αand MitTx-β.
A technique called 'patch clamping' was used to identify the particular protein paths in cells that react to acid, called acid sensing ion channels (or ASIC subtypes), that the venom acted upon. Further testing on mice also helped the researchers to ascertain whether the ASIC subtype they had identified was actually responsible for causing pain.
A surprising response
The team discovered that the two main active ingredients in Texas coral snake venom (MitTx-αand MitTx-β) were 'house-keeping' enzymes that individually do not create a pain response. It was only in the form of a complex mixture that these two enzymes were capable of the painful reaction found from Texas coral snake bites.
They also found that a pathway named ASIC1 was activated by this particular venom, with a different pathway named ASIC2 being agonised if conditions become more acidic. This was unexpected, as previous research had only seen action on a completely different pathway, called ASIC3. The researchers are hoping this discovery will allow them to identify the role that these new pathways could have in pain-relieving medicine.
Bryan Fry from the Venom Evolution Laboratory at the University of Queensland in Brisbane commented on the significance of this research saying, "This highlights the tremendous biodiscovery potential of venoms not only for understanding the fundamentals of how the human body works, but also representing a rich treasure trove of novel compounds for use in drug design and development."
Fry pointed out that is not the first time that a venomous creature has been responsible for medicinal progress. "The next wonder-drug may come from the most unlikely of sources. Such has already been the case," he said. "For example, if you know of anyone with high blood pressure, odds are they are taking a member in the ACE-inhibitor family. [This is] a drug class whose importance cannot be over-stated, having saved countless lives while also being a multi-billion dollar industry. The founding member of this entire drug class was a modified version of a snake toxin."
