Scientists at University of California, San Francisco have identified two toxins from the venom of the heteroscodra maculate tarantula spider that selectively activate a sodium channel involved in pain.
The discovery could further the understanding of pain and how the channels work; and provide a new potential tool to manipulate sodium channels connected to neurological disorders unrelated to pain, such as Alzheimer’s disease.
The research paper, “Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain”, was published in Nature.
Voltage-gated sodium (Nav) channels are involved in the action potential initiation in most neurons, including the nerve fibers of the pain pathway. Anaesthetics block pain by non-specific action at all Nav channels.
Finding molecules and drugs that could more specifically act on individual channels has several beneficial effects including preservation of other sensations while specifically manipulating nerve fibers, and better understanding how individual subtypes of the channels contribute to chemical, mechanical, or thermal pain.
The present study was led by researchers in the lab of Dr. David Julius, renowned for the discovery and characterization of the “wasabi receptor”.
The scientists have been screening hundreds of venoms from poisonous spiders, scorpions, and centipedes. All of the creatures have naturally evolved chemical defenses that target the very biology of other animals’ pain nerves.
“There are dozens to hundreds of different active peptides in each animal’s venom,” said Dr Julius, in a news release. “The deeper you look the more toxins there seem to be.”
In order to identify the chemicals in the tarantula’s venom that were specifically targeting the pain channels, the researchers separated the chemicals and administered them individually to rodent sensory neurons. The scientists then identified two peptides that specifically activated the sensory nerves.
Lab-synthesized versions of the molecules confirmed the ability to individually activate pain-sensing neurons and bind to a particular receptor that is found on A-delta nerves in mice, described like the sharp pain from a burn or a cut. The peptides also allowed researchers to isolate the fibers in mice and discover that they may also play role in touch hypersensitivity – such as pain felt from the mere brush of a fingertip.
The researchers also noted findings from a pharmacology perspective.
“These channels are incredibly hard to identify drugs for because the different subtypes are closely related, making it difficult to identify drugs or other agents that act on one subtype and not another,” Julius said. “These toxins provide unique tools to start understanding exactly what this particular subtype, Nav1.1, does in terms of pain sensation.”
