Crotalphine is an analgesic peptide identified from the venom of Crotalus durissus terrificus, a South American rattlesnake. Although its anti-nociceptive effect is well documented, its direct mechanisms of action remain poorly understood and, in particular, its molecular targets are not clearly identified. Knowing that the activity of sodium channels expressed in the dendrites of sensory neurons (nociceptors) in the dorsal root ganglion (DRG) is involved in the sensation of pain, the researchers evaluated the action of crotalphine on the NaV1.7 subtype of sodium channels, a target genetically validated as being involved in nociception. They show that crotalphine i) effectively inhibits sodium current (electrophysiological measurements on mouse DRG neurons), and ii) produces a significant decrease in the viability of cultured epithelial cells and primary cultures of DRG neurons.
These results demonstrate the efficacy of crotalphine in acting on a sodium channel subtype, a potential additional target contributing to the peptide's analgesic properties, and, for the first time, on a second target, a component of the cell plasma membrane, yet to be identified.
DRG (Dorsal Root Ganglion) neurons : The sensation of pain can be initiated by nociceptor cells, which are sensory neurons whose cell bodies are located in the dorsal root ganglia (DRG) or spinal ganglion.