Big things happen in small rodents: grasshopper mice as a model for the evolution of pain resistance

This post is written by MSU grad student Lauren Koenig

Lauren Koenig trapping small mammals for a previous field project in Colorado

Life in the desert is full of extremes. Daytime temperatures are scorching, monsoon rains are torrential, and plants are sparse and spiky. Yet many desert animals, such as grasshopper mice (Onychomys torridus) and pinacate beetles (Eleodes longicollis), are able to thrive in these conditions.

So what is the key to survival? For these species, it is the development of extreme adaptations in response to their environment, as well as to each other.

The evolution of adaptations and counteradaptations between two species is known as an evolutionary arms race. This phrase may aptly bring to mind an image of two countries duking it out, building bigger and better nuclear missiles. In the case of mice vs. beetles, the beetle’s missile is a nasty chemical spray consisting of benzoquinones and the launchpad is at the base of its abdomen. When threatened, pinacate beetles will do a headstand, a position best suited to target an oncoming predator’s eyes, nose, and mouth. While pinacate benzoquinones are not deadly to humans, they wreak havoc on sensitive tissue. For a much smaller mammal, benzoquinones will burn and blind on an even more intense level.

A grasshopper mice attacks a pinacate beetle

In turn, the grasshopper mouse appears to have evolved a superhero trait of its own. The well-known entomologist Thomas Eisner first described this attack and claimed that grasshopper mice avoid being sprayed by placing the beetles butt-end in the sand so that the glands discharge harmlessly into the soil1. I’m not so sure that the case is so cut and dry, however. Using its front paws, the mouse will try and grab the beetle, keeping it still long enough to take an incapacitating bite. This manipulation isn’t enough to prevent an onslaught of chemical spray to the face and the mice show signs of discomfort (i.e. grooming, burying behavior). Both Eisner and I can agree, however about the truly remarkable end to this battle. Grasshopper mice are not deterred from their pursuit. They are swift, vicious, and persistent carnivores. The desert floor is littered with the empty shells of pinacate beetles that met a similar demise at the hands of the only rodent species that seems to consistently withstand the spray. Deer mice, the facultatively insectivorous cousins that share the same habitat and encounter the same insects as grasshopper mice, are much less persistent in their pursuit of pinacate beetles and consume them far less often2.

So what makes grasshopper mice such rare rodents? What secrets lie in their physiology that make them less like Mickey Mouse, and more like Monty Python’s killer rabbit?

It turns out that grasshopper mice have some very weird and fascinating responses to pain. In addition to pinacate beetles, they prey on all the classic horror film stars, like tarantulas, centipedes, and bark scorpions, which possess one of the most painful stings. An elegant study by Drs. Ashlee and Matt Rowe discovered that scorpion venom binds to a sodium channel receptor that switches the venom’s effect from pain to that of an analgesic3. Essentially, the mice use the scorpion’s own defense mechanism as the very tool that allows them to successfully eat scorpions, no matter how many times the mice are stung. Deer mice, in comparison, won’t survive long after the first sting.

Benzoquinone, however, does not target sodium channels. It is likely that benzoquinone targets TRPA1, a conserved calcium channel in the nose and mouth that is found across the animal kingdom, ranging from humans to drosophila. It mediates reception of pain, temperature, touch, spice, and caffeine, among others. This is an excellent starting point to begin exploring the mechanism for pain resistance in grasshopper mice – we know that they exhibit reduced sensitivity to formalin, another TRPA1 agonist3. TRPA1’s versatility ensures that any organism that develops an antipredator system through TRPA1 disruption could target many predators with a single stroke.  In response, a predator that had a modified TRPA1 channel immune to that disruption could take advantage of prey that is inaccessible to most of its competition.

Here is where things get interesting. There’s a reason why most animals have not evolved resistance to pain. Pain serves a critical function in the nervous system to warn the body of potential damage (i.e. it tells you not to walk on a broken foot so that the foot can heal). Prey, like scorpions, take advantage of this in order to signal that they are harmful. If an animal lives to eat again it likely learns to never, ever try and eat a scorpion – and that’s a good thing for both the predator and the prey. Therefore, the crucial function of pain in survival ensures that natural selection favors pain sensitivity. So how and why do pain-pathway adaptations exist?  

It is at the junction of this paradox that I aim to pursue my graduate research. By studying grasshopper mice as the exception to the pain-pathway standard, I hope to learn about the underlying mechanisms behind their pain tolerance.

Why should we care about a rodent sized war happening in the middle of the Arizona desert? As researchers discover more about TRPA1, we’re realizing that this receptor plays an even more integral role in the nervous system than previously thought. TRPA1 receptors serve many types of functions and are found even in humans. Not all the signals they send are welcome, however, as TRPA1 is involved in inflammatory, neuropathic, and migraine pain, as well as airways diseases and diabetes4. The more we learn about TRPA1, the more we can learn about our own responses to pain and how to block it. By studying animals in which pain blockage is successful, perhaps we too can someday swallow a pill-sized dose of grasshopper mouse superpowers.


  1. Eisner, T., & Meinwald, J. (1966). Defensive Secretions of Arthropods. Science, 153(3742),1341–1350.
  1. Parmenter, R. R., & Macmahon, J. A. (1988). Factors limiting populations of arid-land darkling beetles (Coleoptera: Tenebrionidae): predation by rodents. Environmental Entomology, 17(2), 280-286.
  1. Rowe, A. H., Xiao, Y., Rowe, M. P., Cummins, T. R., & Zakon, H. H. (2013). Voltage-gated sodium channel in grasshopper mice defends against bark scorpion toxin. Science, 342(6157), 441-446.
  1. Nassini, R., Materazzi, S., Benemei, S., & Geppetti, P. (2014). The TRPA1 channel in inflammatory and neuropathic pain and migraine. In Reviews of Physiology, Biochemistry and Pharmacology, Vol. 167 (pp. 1-43). Springer International Publishing.
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