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Centipede venom yields powerful pain relief

Medical ResearchScience

The Chinese red-headed centipede is one of those creepy-crawlies you might run from. But its venom appears to hold potentially powerful medicine against pain, a group of researchers in Australia and China has found.

Properly distilled and purified, the arthropod's venom proved a more potent analgesic in mice than morphine, and at doses 10 time higher than those used, appeared to have no physiological side effects such as changes in heart rate or blood pressure. That makes the colorful centipede's venom more promising as a painkiller than certain spider venoms, which operate on the same mechanism but which also affected heart function, muscles and nerves in ways that made the venoms fatal to rats.

The newest study on venom's potential medicinal powers was published Monday in the Proceedings of the National Academies of Sciences. It comes against a backdrop of mounting interest in the potential biomedical uses of venom from many sources.

The Chinese red-headed centipede is one of some 3,300 species of centipedes, one of the most ancient arthropods creeping and crawling the earth. They kill their insect prey by grasping them with a pair of pincers and releasing venom from those forcipules, instantly paralyzing the insect.

In mammals, however, centipede venom has unique properties. It contains peptides that alter the way certain cells function. Specifically, it is a powerful and very targeted inhibitor of a protein needed by the cells that carry pain signals up the spinal cord and into the brain.

The protein on which the centipede venom works is the same one that malfunctions in people born with a very rare inherited disorder that makes them insensitive to pain. In some 20 cases reported in scientific literature, a person with a mutation in the gene that codes for part of these proteins can feel the difference between sharp and dull and hot and cold. But he or she does not perceive the sensation of physical pain.

These people -- who also lack a sense of smell -- often die prematurely because their insensitivity to pain leaves them vulnerable to burns, wounds and accidents of all sorts. At the same time, people with a genetic mutation that results in too much of the protein, called voltage-gated sodium channel 1.7,  can suffer from neuropathy and debilitating bouts of pain. 

Researchers hit upon the centipede's venom as a potential analgesic agent because it worked very specifically on the protein that influences pain sensation, and not on related ones that affect heart function. They tried it on mice who were subjected to three types of pain: internal pain caused by the injection of acetic acid in the belly; foot pain induced by the injection of formaldehyde into the pads of the rodents' paws; and the application of painful heat to the tails of the mice.

Mice that were given an injection of the purified centipede venom showed substantial reductions in the behaviors that typically indicate they are suffering pain, such as paw-licking, withdrawal of the tail from the heat source, and abdominal writhing.

In dealing with the internal pain of acid in the stomach and the external pain of heat to the tail, mice that got the centipede venom did as well as those that got equivalent doses of morphine. Mice that got centipede venom showed a greater tolerance for the pain of formaldehyde in their paws than did mice that got the same dose of morphine.

Toxins that occur naturally have been a hot topic of drug research in recent years. The toxin that the cone snail uses to paralyze its prey has produced one drug, an analgesic called ziconotide, which treats neuropathic pain that morphine fails to blunt. ACE inhibitors as a treatment for heart disease emerged from research on snake venoms.

The Malayan pit viper's venom is thought to have a powerful anticoagulant effect that could become part of stroke therapies. A component in the venom of the Brazilian arrowhead viper may prevent the constriction of blood vessels, making it a possible blood pressure drug. Other proteins in snake venom are being used to investigate how receptors of certain brain cells respond to nicotine and other addictive substances.

More recently, researchers have investigated the potential of the giant yellow Israeli scorpion's venom in battling the deadly brain cancer glioma.

 

Copyright © 2014, Los Angeles Times
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