02 December 2013

Rodents Show Path To Possible New Class Of Painkillers

The Arizona Tree Bark Scorpion has a venom that works on the principle of pure pain.  Unlike, for example, the venom of a brown recluse spider, this scorpion's venom doesn't actually do much damage to tissue or biological processes necessary to survival.  Instead, a protein in the venom opens what is called a sodium channel that activates a pain signal in the nervous system and causes it to cascade across pain receptors all along the bite area.  The venom is also notable because it has a particularly strong effect in mammals of all kinds, including humans.  While the dosage of this tiny scorpion is merely a vicious sting in an adult, it can kill small children.

A carnivorous mouse species in Arizona called a grasshopper mouse that eats these scorpions and other arthropods has a defense to this venom.  It has a protein that reverses the signal that the protein in the scorpion venom usually triggers.  In these mice, the scorpion venom interacting with the mouse protein closes the sodium channel and effective shuts off all pain receptors in the area affected by the venom.

Once the venom has shut down the pain receptors in the affected area, the mouse in numb to all sources of pain in the affected area, even those unrelated to the venom.

The African naked mole rat, which lives in a highly acidic environment, has a similar biochemical mechanism in its body that shuts down the pain receptor sodium channel that would normally be triggered by its environment.

The unstated implication of these discoveries is that if one could replicate protein combinations that shut down the sodium channel to pain receptor activation in the Arizona grasshopper mouse and African naked mole rat, that one could create a new class of local anesthetic pain killers that utilize this biochemical pathway.  Since we have real world examples of the proteins that block these channels, in principle, it ought to be possible to either harvest it from mice or rats bred for that purpose, or to synthetically generate it, with a minimum of trial and error.  Indeed scientists have been able to reconstruct Nav 1.8 (the protective protein in Arizona grasshopper mice) in the lab.

My source was Science News (print copy) but National Geographic also covers the story (albeit less lucidly). Ultimate source: Rowe, Xiao, Rowe, Cummins & Zakon. 2013. Voltage-Gated Sodium Channel in Grasshopper Mice Defends Against Bark Scorpion Toxin. Science http://dx.doi.org/10.1126/science.1236451

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