Mental Floss

Tarantula Venom Tapped for New Kind of Painkiller

Jordan Rosenfeld

The Peruvian green velvet tarantula, whose venom shows promise as an inhibitor of the reception and transmission of pain. Image credit: Tarantuland via Flickr // CC BY-NC 2.0

Most of us fear venomous creatures like spiders and scorpions for good reason—venom delivered straight from the source can cause life-threatening reactions and death. However, within venoms themselves are potentially therapeutic peptides that have been shown to block some pain receptors in mice and humans. This new class of painkillers could be the first real breakthrough in treating drug-resistant chronic pain without addictive side effects.

New research recently presented at the Biophysical Society’s 60th Annual Meeting in Los Angeles revealed the mode of action of the venom derived from the Peruvian green velvet tarantula, Thrixopelma pruriens, which is considered especially potent to inhibit the reception and transmission of pain through voltage-gated sodium channels, such as NaV 1.7, 1.8, and 1.9.

The tarantula venom, called Pro-Tx II, was first identified at Yale in 2014, after culling 100 other spider venoms, for its potential in dulling pain-sensing neurons. “We set out to understand if the cell membrane itself is important in the peptides’ mode of action,” Sonia Troeira Henriques, senior research officer at the University of Queensland Institute for Molecular Bioscience, tells mental_floss.

Using lab-cultivated neuroblastoma cells, which were modified to express the NaV 1.7 pain receptor, researchers obtained a 3D view of the peptides’ structure under nuclear magnetic resonance (NMR) so they could closely observe how and if the toxin was binding to the cell membrane.

“What we found is that the cell membranes of neuronal cells attract the peptides to a close vicinity of pain target receptors and orient the peptides with the right position to bind to the target,” Henriques says. In other words, the peptides have the perfect chemical composition to bind to the phospholipid layer of the cell. Prior research had suggested that the peptides’ ability to bind to the lipid membrane might be responsible for inhibiting the NaV 1.7 pain receptor. “But we are the first one showing that correlation,” she says.

The NaV 1.7 pain channel is one of several subtypes in cell membranes responsible for controlling the ions that come and go from the cell. NaV 1.7 is expressed only in neuronal cells, but, says Henriques, “there are other channels of the same family expressed in the cardiac muscles. Because they are so similar we have to make sure the peptide we are working with is selective to the pain target and not the cardiac muscles, because if you inhibit cardiac muscles, the person won’t survive.”

If it makes it into therapeutic form, Pro-Tx II won’t be the first commercially viable toxin-derived pain reliever; an existing drug called Prialt, designed from the venom of marine snails, is often used as a last resort when morphine doesn’t stop chronic pain. As of yet, making any venom-based painkillers available in a pill form may take a while to develop, because currently these peptide molecules don’t cross the blood-brain barrier, necessitating an injection to the spine.

As to the effectiveness of pain relief provided by the venom-based painkillers, Henriques says, “Some studies have compared the pain behavior of those mice when they are injected with this toxin versus regular painkillers and they are comparable in terms of efficiency and in the way they relieve pain.”

The next stage of research is to try to improve the mode of action so that more pain-blocking peptides can be attracted to a given pain receptor, for greater effectiveness.

Henriques remains hopeful. “What keeps me going, and what I like in this work, is that every single piece of knowledge we bring to this field will be converted into a product that will improve someone else’s life.”

Editor's note: This post has been updated to clarify the pain receptor focused on in the study. It is NaV 1.7, not NaV 1.8.