Voltage-Gated Sodium Channel in Grasshopper Mice Defends Against Bark Scorpion Toxin

Bite Me! As unpleasant as it is, pain serves a purpose, to alert the body to potential damage. This protective function may explain why few predators have evolved resistance to the painful venoms used as a defense by their prey. The grasshopper mouse, however, is insensitive to one of the most painful stings in the animal kingdom—that of the bark scorpion. Rowe et al. (p. 441; see the Perspective by Lewin) now show that grasshopper mice use the toxins present in the scorpion venom to block voltage-gated pain transmission, temporarily reducing their sensitivity to nonvenom-induced pain. Thus, grasshopper mice use the scorpion's painful defense to their advantage and have evolved a mechanism that allows for reduction of pain sensitivity only when it is needed. Grasshopper mice use the scorpion’s strength against it—instead of inducing pain, scorpion venom blocks pain. [Also see Perspective by Lewin] Painful venoms are used to deter predators. Pain itself, however, can signal damage and thus serves an important adaptive function. Evolution to reduce general pain responses, although valuable for preying on venomous species, is rare, likely because it comes with the risk of reduced response to tissue damage. Bark scorpions capitalize on the protective pain pathway of predators by inflicting intensely painful stings. However, grasshopper mice regularly attack and consume bark scorpions, grooming only briefly when stung. Bark scorpion venom induces pain in many mammals (house mice, rats, humans) by activating the voltage-gated Na+ channel Nav1.7, but has no effect on Nav1.8. Grasshopper mice Nav1.8 has amino acid variants that bind bark scorpion toxins and inhibit Na+ currents, blocking action potential propagation and inducing analgesia. Thus, grasshopper mice have solved the predator-pain problem by using a toxin bound to a nontarget channel to block transmission of the pain signals the venom itself is initiating.