Pinch away the pain: Scorpion venom could be an alternative to morphine

Prof. Michael Gurevitz of Tel Aviv University's Department of Plant Sciences is investigating new ways for developing a novel painkiller based on natural compounds found in the venom of scorpions. These compounds have gone through millions of years of evolution and some show high efficacy and specificity for certain components of the body with no side effects, he says.

Peptide toxins found in scorpion venom interact with sodium channels in nervous and muscular systems -- and some of these sodium channels communicate pain, says Prof. Gurevitz. "The mammalian body has nine different sodium channels of which only a certain subtype delivers pain to our brain. We are trying to understand how toxins in the venom interact with sodium channels at the molecular level and particularly how some of the toxins differentiate among channel subtypes.

"If we figure this out, we may be able to slightly modify such toxins, making them more potent and specific for certain pain mediating sodium channels," Prof. Gurevitz continues. With this information, engineering of chemical derivatives that mimic the scorpion toxins would provide novel pain killers of high specificity that have no side effects.

An ancient Chinese secret?

In his research, Prof. Gurevitz is concentrating on the Israeli yellow scorpion, one of the most potent scorpions in the world. Its venom contains more than 300 peptides of which only a minor fraction has been explored. The reason for working with this venom, he says, is the large arsenal of active components such as the toxins that have diversified during hundreds of millions of years under selective pressure. During that process, some toxins have evolved with the capability to directly affect mammalian sodium channel subtypes whereas others recognize and affect sodium channels of invertebrates such as insects. This deviation in specificity is for us a lesson of how toxins may be manipulated at will by genetic engineering, he says.

While the use of scorpion venom to treat some body disorders seems counter-intuitive, the Chinese have recognized its effectiveness hundreds of years ago. "The Chinese, major practitioners of what we call 'alternative medicine,' use scorpion venom, believing it to have powerful analgesic properties," Prof. Gurevitz says. Some studies have also shown that scorpion venom can be used to treat epilepsy. "We study how these toxins pursue their effects in the Western sense to see how it could be applied as a potent painkiller."

Using an approach called "rational design" or "biomimicry," Prof. Gurevitz is trying to develop painkillers that mimic the venom's bioactive components. The idea is to use nature as the model, and to modify elements of the venom so that a future painkiller designed according to these toxins could be as effective as possible, while eliminating or reducing side effects.

No more morphine addicts

Finding a new and effective pain medication could solve one of the biggest problems in the medical world today. Pain is an important physiological response to danger, physical injury and poor health, yet doctors need to reduce extreme pain in patients which aspirin could never palliate. To date, opiate-derived painkillers have been quite effective, but the medical community is eager to find other solutions due to the risks associated with their use.

"This new class of drugs could be useful against serious burns and cuts, as well as in the military and in the aftermath of earthquakes and natural disasters. Instead of running the risk of addiction, this venom-derived drug, mimicking the small peptide toxin, would do what it needs to do and then pass from the body with no traces or side-effects," Prof. Gurevitz says.