Venomous bites can be deadly when left untreated, but venom also has a medical upside. Scientists, for instance, have recently started tapping peptide toxins for targeting brain receptors to potentially act as painkillers.
Researchers from Australia’s University of Queensland revealed their use of ProTx-II, a peptide toxin found in the Peruvian green velvet tarantula, and its capacity for inhibiting the pain sensation receptor, making it a prospective painkilling alternative in the future.
Sónia Troeira Henriques, researcher at the Institute for Molecular Bioscience of the university, explained that ProTx-II is known to bind to the pain receptor in the membrane of the cells in the neurons, yet the precise binding site as well as the role of the cell membrane in the toxin’s beneficial action were not yet known.
The team then explored ProTx-II’s structure and activity using nuclear magnetic resonance spectroscopy. They also used other techniques such as molecular simulations in order to see how the toxins interact in cell membranes.
"The neuronal cell membranes attract the peptide [toxin] 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," explains Henriques.
According to the research, previous studies practically ignored this important role of the cell membrane in ProTx-II’s actions. For the first time, it was revealed that the membrane-binding action, for instance, enhances its ability to inhibit Nav 1.7, which is a highly noted pain receptor.
The toxin also interacted with cellular structures involved in pain, blood pressure regulation, and muscle and nerve relaxation, enabling new medicinal targets for treating neuromuscular, neurological and other pain-related disorders.
The goal now is to design molecules for pain management with fewer or no side effects.
The team will present their findings at the Biophysical Society’s 60th Annual Meeting in California held Feb. 27 to March 2.
Millions of individuals worldwide live with chronic and neuropathic pain. Chronic pain is defined as pain lasting over 12 weeks, and may result from injury such as a back sprain or an ongoing illness.
The current range of treatments include medications, electrical stimulation therapy, acupuncture, nerve blocks, and surgery – some of which provide limited improvements, come with side effects, or even lead to extreme addiction.