The search for safer, more effective and non-addictive painkillers has led scientists to an unlikely source: tarantula venom. More specifically, a single compound found in the venom of the Peruvian green velvet tarantula, which has been found to inhibit a particular pain receptor on the membrane of neuronal cells. By examining how this molecule works, researchers hope to open up new possibilities for the creation of synthetic painkillers.

The compound in question is a peptide called ProTx-II, which previous studies have shown to bind to the pain receptor – or nociceptor – Nav 1.7. However, the mechanisms by which ProTx-II interacts with the neuronal membrane in order to affect this receptor had until now remained unknown.

Delivering a talk at the Biophysical Society’s 60th annual meeting, scientists from the University of Queensland presented new research into this conundrum, describing how they used an analytical technique called nuclear magnetic resonance spectroscopy in order to create 3-D representations of the peptide. In doing so, they were able to characterize and examine its structure in detail and identify key binding sites that are likely to interact with the neuronal membrane.

At the same time, they used fluorescent trackers in order to observe exactly how these interactions occur in real life, gaining a thorough overall understanding of how ProTx-II finds its way to the Nav 1.7 nociceptor.

“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 lead researcher Sónia Troeira Henriques.

Nav 1.7 is a voltage-gated ion channel, proteins that control the passage of positively and negatively charged atoms and molecules across membranes. Understanding how the cell membrane interacts with peptide toxins that target voltage-gated ion channels gives researchers a useful platform for designing new drugs that act upon these receptors.

By using this opportunity to create new painkillers, it may be possible to replace opioid drugs, which are currently prescribed for reducing pain but are highly addictive and also produce a number of negative side effects such as drowsiness or respiratory depression in cases of overdoses.