Green tarantula venom could hold the key to new types of pain control.
Image credit: Henriques, University of Queensland.
If a human gets bitten by certain spiders, snakes or cone snails, the venomous toxins can be potent enough to kill or, at least, cause a serious reaction.
Meanwhile, millions of people worldwide live with chronic and neuropathic pain, which current treatments only partially relieve. The existing therapies can also cause severe drowsiness or other sleep problems and can be highly addictive.
Researchers have therefore been hunting down potential candidates that could offer a better solution. They are also seeking a greater understanding of exactly how molecules act to reduce pain.
New and alternative painkillers could improve the quality of life of many people who experience chronic pain.
As part of this effort, a team from the University of Queensland in Brisbane, Australia has been investigating ProTx-II, a peptide toxin found in the venom of the Peruvian green velvet tarantula, Thrixopelma pruriens.
Characteristics of ProTx-II include high potency and selectivity to inhibit the pain sensation receptor. These factors, the team says, make it an ideal candidate as a future painkiller.
Scientists already knew that ProTx-II binds to the pain receptor located within the membrane of neuronal cells. What has remained unclear, however, is where the binding takes place, or what role the cell membrane plays in inhibiting the activity of ProTx-II.
How does ProTx-II inhibit the pain receptor?
To find out more, the researchers have been looking at the structure, the membrane-binding properties and the inhibitory activity of ProTx-II and a number of analogs.
They used nuclear magnetic resonance (NMR) spectroscopy to collect 3D evidence that enabled them to examine the structure and its role in inhibiting the pain receptor.
The scientists wanted to find out how the peptide and the neuronal cell membrane interact. They also hoped to identify the molecular properties of the peptide that interacted with and inhibited the pain receptor. To do this, they used surface plasmon resonance and fluorescence methodologies, as well as molecular simulations.
The results indicate that the cell membrane plays an important part in enabling ProTx-II to inhibit the pain receptor. The neuronal cell membranes attract the peptide to the neurons, intensifying its concentration close to the pain receptors. The peptide then locks in the right orientation to allow maximum interaction with the target.
This is the first study to describe the importance of the membrane-binding properties of ProTx-II for its potency as an inhibitor of Nav 1.7, an important pain receptor.
Sónia Troeira Henriques, senior research officer at the University of Queensland's Institute for Molecular Bioscience, explains that finding out more about how this toxin works could help with the design of new pain therapeutics.
Medical News Today asked Henriques if other creatures could offer the same benefits.
She told us:
"Many toxins have been isolated from venoms from several creatures, e.g. cone snails, spiders, anenome, etc., and have been found to bind to pain sensation receptors. A very famous case is the toxin Prialt, or Ziconotide, that is a marketed drug used as analgesic and it was first identified in a cone snail."
Apart from Nav 1.7, the cell membrane contains other channels that are implicated in a number of physiological processes, such as muscle and nerve relaxation, blood pressure regulation and sensory transduction.
Since these functions are associated with various disorders, the researchers hope their discoveries will reveal new targets for treating neuromuscular disease, neurological disorders and inflammatory and neuropathic pain.
They are now working on new toxins with greater affinity for the cell membrane and reduced side effects.
Two venomous spiders found in the US include the black widow and the brown recluse, mostly in the Southern and Western or Midwestern states. While rarely causing death, a bite can cause symptoms ranging from a rash to difficulty breathing and high blood pressure. Bites will need medical attention.
MNT reported last year on other research showing that venom from spiders could block pathways to reduce pain.