The molecular mechanisms underlying the severe pain response induced by Old World spider venoms are unclear.

The researchers analyzed venom from King Baboon spiders (Pelinobius muticus), which are large tarantulas found in Kenya and Tanzania.

The authors used proteotranscriptomic analysis to identify an inhibitory peptide that was abundant in P. muticus venom. Next, the authors synthesized the peptide and used NMR spectroscopy to determine its 3D structure.

The authors analyzed the effects of the synthetic peptide in dissociated mouse sensory neurons. In the dissociated mouse neurons, the peptide modulated multiple voltage-gated ion channels, enhanced excitatory sodium currents, decreased inhibitory potassium currents, and resulted in pain.

The authors also performed mathematical modeling of the peptide’s effect on pain neurons to corroborate the findings. The authors suggest that the spiders use a single peptide to target multiple receptors as an economic and effective way to evoke pain as a defense strategy.

According to the authors, the results could inform the development of treatments for chronic pain

https://www.pnas.org/content/119/5/e2110932119