Tarantulas May Help Develop New Pain Medication

By Pat Anson, PNN Editor

Venom from a bird-catching Chinese tarantula may hold the key to medications that could someday block pain signals in humans, according to a new study at the University of Washington School of Medicine. Researchers say the oversized, hairy spiders inject a toxin into the birds that quickly immobilize them.

"The action of the toxin has to be immediate because the tarantula has to immobilize its prey before it takes off," said William Catterall, PhD, a professor of pharmacology and lead author of a study published in the journal Molecular Cell.

Catterall and his colleagues were curious how the venom works, so they used a high-resolution cryo-electron microscope to get a clear molecular view of its effect on nerve cells.

They found that tarantula venom contains a neurotoxin that locks the voltage sensors on sodium channels, the tiny pores on cell membranes that generate electric signals to nerves and muscles.

Locked in a resting position, the voltage sensors are unable to activate and the spider’s prey is essentially paralyzed.

"Remarkably, the toxin plunges a 'stinger' lysine residue into a cluster of negative charges in the voltage sensor to lock it in place and prevent its function," Catterall said. "Related toxins from a wide range of spiders and other arthropod species use this molecular mechanism to immobilize and kill their prey."

In humans, sodium channels known as the Nav1.7 channel are essential for the transmission of pain signals from the peripheral nervous system to the spinal cord and brain.

UNIVERSITY OF WASHINGTON

In theory at least, drugs modeled after tarantula venom could be used to target and immobilize the Nav1.7 channel. Previous research has shown that people born without Nav1.7 channels due to genetic mutation are indifferent to pain – so blocking those channels in people with normal pain pathways could form the basis for a new type of analgesic.

"Our structure of this potent tarantula toxin trapping the voltage sensor of Nav1.7 in the resting state provides a molecular template for future structure-based drug design of next-generation pain therapeutics that would block function of Nav1.7 sodium channels," Catterall explained.

While venom-based medicine may sound impractical and more than a little creepy, it’s not unheard of. A pharmaceutical drug derived from cone snail venom is already being used to treat chronic pain. Prialt is injected into spinal fluid to treat severe pain caused by failed back surgery, trauma, AIDS and cancer. Like tarantula venom, Prialt blocks channels in the spinal cord from transmitting pain signals to the brain.  

Spider Venom Could Take Sting out of Chronic Pain

By Pat Anson, Editor

Researchers in Australia have isolated a toxin in the venom of a tarantula that shows promise as a pain reliever. The discovery could accelerate development of a new class of natural painkillers that are not addictive and more effective than opioids.

Thrixopelma pruriens, more commonly known as the Peruvian Green Velvet Tarantula, is native to South America.  The spider’s bite isn’t potent enough to kill humans, but researchers at the University of Queensland say its venom inhibits pain receptors.

"Our group is specifically interested in understanding the mode of action of this toxin to gain information that can guide us in the design and optimization of novel pain therapeutics," said Sónia Troeira Henriques, senior research officer at the University of Queensland's Institute for Molecular Bioscience.

The peptide toxin – known as ProTx-II – inhibits pain signals by binding to the membranes of nerve cells.

image courtesy yale university

"Our results show that the cell membrane plays an important role in the ability of ProTx-II to inhibit the pain receptor. In particular, the neuronal cell membranes attract the peptide to the neurons, increase its concentration close to the pain receptors, and lock the peptide in the right orientation to maximize its interaction with the target," said Henriques.

Henriques and her colleagues were the first to discover the importance of membrane-binding properties of ProTx-II in inhibiting a human pain receptor known as Nav 1.7. Previous research has shown that people born without Nav 1.7 channels due to genetic mutation are indifferent to pain – so blocking those channels in people with normal pain pathways has the potential to “turn off” pain.

University of Queensland researchers have studied the venom of over 200 spider species and found that 40% of the venoms contain at least one compound that blocked Nav 1.7 channels. But they’ve only scratched the surface. There are over 45,000 species of spiders, many of which kill their prey with venom that contain hundreds - or even thousands - of protein molecules that block nerve activity.

Based on the group's findings, they're now designing new toxins with greater affinity for the cell membrane and fewer side effects.

"Our work creates an opportunity to explore the importance of the cell membrane in the activity of peptide toxins that target other voltage-gated ion channels involved in important disorders," said Henriques.

Researchers are also studying the potential of venom in cone snails for its potential for blocking pain signals in humans. German scientists at the Pharmaceutical Institute of the University of Bonn say one advantage of the peptides found in snail venom is that they decompose quickly and are unlikely to cause dependency.

A pharmaceutical drug derived from cone snail neurotoxins has already been developed and marketed under the brand name Prialt. The drug is injected in spinal cord fluid to treat severe pain caused by failed back surgery, injury, AIDS, and cancer.