Using an innovative screening method, a team of scientists from Australia and the United States has discovered a peptide in the venom of the Peruvian green velvet tarantula (Thrixopelma pruriens) that blunts activity in pain-transmitting neurons.
The novel method, named toxineering, has the potential to search millions of different spider toxins for safe pain-killing drugs and therapies.
Dr Michael Nitabach from Yale School of Medicine and his colleagues screened toxins from a variety of tarantula species to find one that blocked TRPA1, an ion channel on the surface of pain-sensing neurons that is implicated in inflammation and neuropathic pain.
By generating a small library of mutated versions of the tarantula toxin, they identified Protoxin-I – a 35-residue peptide from the venom of the Peruvian green-velvet tarantula – that blocks TRPA1 but has no effect on activity of other channels on the surface of neurons.
“The beauty of the system is we can also screen engineered toxins not found in nature, and identify higher-potency and more specific molecular variants that lack deleterious effects on essential nerve functions,” said Dr Nitabach, who is the lead author of a paper published in the journal Current Biology.
“The likelihood is that within the vast diversity of spider toxins we will find others that are active against other channels important for pain,” he said.
The team plans to ramp up efforts to test tens of thousands of new toxins for similar biological activity against pain-sensing neurons.
Junhong Gui et al. A Tarantula-Venom Peptide Antagonizes the TRPA1 Nociceptor Ion Channel by Binding to the S1–S4 Gating Domain. Current Biology, published online February 13, 2014; doi: 10.1016/j.cub.2014.01.013