In Pain? Try Some Poisonous Snail Venom

By Leana Shugol • Jan 29th, 2014 • Category: Features

A recent study conducted by the U.S. Department of Health and Human Services states that more than 22 million Americans use illegal drugs. Of these, seven million people use psychotherapeutic drugs such as painkillers, tranquilizers, and sedatives.

According to government data found on WebMD.com, 1.7 million people in the U.S. were found to be using psychotherapeutic drugs in 2007. Comparing the two studies shows that there has been a five-fold increase in prescription drug use within only five years’ time. Robert Jamison, PhD, associate professor at Harvard Medical School, says, “The increase is partly an issue of availability.”

Responding to their patients’ requests, doctors have become less restrictive in prescribing opioid pain pills. “But even with its increased use, doctors have not gotten any better at treating pain,” says Anthony Rivas, researcher and reporter for Medical Daily.

Besides the possibility of addiction, painkillers have numerous side effects, such as nausea, dizziness, fatigue, headache, heart attack, stroke, liver damage, among many others. Seeking to curb these side effects, scientists have begun to look elsewhere in hopes of biomedical breakthroughs in pain management.

Centuries ago, it was noted that certain components of snake, snail, bee, and scorpion venom can be used to treat pain. However, it wasn’t until the 20th century that complete discoveries have been made.

Before jumping into the details of how venom can treat pain, we must first understand how pain works. After an injury has occurred, special pain receptors called nociceptors sense the mechanical, thermal or chemical stimuli and send it to the central nervous system, which eventually sends the signal to the brain.

But what is this “signal”? The signal is essentially caused by ions (positively or negatively charged particles), which are transmitted across ion-channels embedded within the cell membranes of neurons. These channels are controlled by charge (voltage) or the number of ions (concentration) on either side of the gate.

Venom works by modulating (propagating or inhibiting) the movement of sodium (Na+) or calcium ions (Ca2+) across the ion-gated channels. Usually, the toxins in the venom keep the gates excessively open or closed; this determines whether nerve impulses will continue to travel through the body.

Dr. Mandë Holford, Assistant Professor of Chemical Biology at the City University of New York, studies a particular species of marine cone snails, which she believes can bring us the next breakthrough in treating chronic pain.

The toxins produced by snails can kill a human within seconds, yet, paradoxically, a smaller dosage or a solution containing those same toxins can be an efficient way to treat pain in humans.

Most of the time, poisonous animals do not produce the toxins on their own, but rather, it’s part of their biology. The toxins are believed to be medium-sized chains of amino acids, those same amino acids that are called the “building blocks of life.” The gene that codes for the toxin in the snail’s DNA is first transcribed into an RNA strand and then translated into the protein (the chain of amino acids).

Because only a small amount of venom can be extracted from each snail, Dr. Holford is trying to find a way to artificially synthesize this sequence of amino acids, bypassing DNA and RNA synthesis. Also, Holford is trying to find out if there are any unnecessary amino acids that can be cut out of the peptide chain, leaving the toxin with the same pain-killing effects. This step is necessary for practical drug development, because synthesis of long peptide chains is expensive and inefficient.

Also, with the ability to synthesize peptide chains “we can make bucket loads at a time, and then have the luxury of being able to modify the toxins any way we want, and screen them quickly to see which version has the most promising effects,” says Zoltan Takacs, PhD, a researcher for the National Geographic Society.

Cone snail venom has already been incorporated in a drug called Ziconotide, which serves to relieve severe chronic pain in cancer and HIV patients. It was approved for sale under the common name “Prialt” by the U.S. Food and Drug Administration in late 2004, after 30 years of research led by one man, Baldomero Olivera and his team of researchers at the University of Utah. Prialt is a synthetic form of a ω-conotoxin peptide found in a particular species of cone snails called conus magnus. This toxin is hypothesized to be 1,000 times more effective than morphine, but does not possess the additive traits that morphine does.

Dr. Holford is hoping for a similar discovery with her own species of snails called terebrids and turrids. She believes that the discovery of Prialt is “proof that neurotoxins can be used for other drug developments as well.” Holdford’s long-term goal, along with many other scientists’ goals, is to extend the benefits of natural venom to other medical applications; “for example to treat epilepsy or heart disease,” Holford says.

Research conducted by the Institute of Medicine (IOM) claims that over 116 million Americans are affected by serious, chronic pain each year. This statistic makes pain relief one of the largest areas of study in United States.

Another study published by Archives of Internal Medicine, show that most people addicted to pain pills are family or friends of those using them for medical purposes.

By decreasing the number of painkiller prescriptions given by doctors, we decrease their availability, and thus the number of people using them for medical and non-medical purposes.

Over the last 50 years, research on venom as pain treatment has become a tremendous trend. Hundreds of articles have been published claiming the positive effects of venom, in opposition to common belief that it can only be malignant to humans.

Alla Rivkina, MD, a neuroscience professor at Riga’s Medical University of Stradina, says “my colleagues and I see a bright future in toxin-incorporated medications. We expect major breakthrough discoveries in the near future.”

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