The grasshopper mouse has a unique
ability, one that is seemingly maladaptive, but is unarguably incredible. When
stung by a bark scorpion, grasshopper mice do not recoil in pain, as is the
response in other organisms, but instead they retaliate by attacking the
scorpion and eating it. This is so out of the ordinary that studies were done
to see why exactly the mice were responding this way, and specifically, why
they seemed to feel no pain from the poisonous scorpion sting. Scientists
isolated nociceptors from the grasshopper mice, which are neurons that are involved
in pain response. By injecting an electrode into the neuron to determine its electrical
response to stimuli, experimenters were able to observe how the neurons reacted
when they exposed the scorpion venom to the extracellular fluid. Action
potentials did not fire in the nociceptors when they were exposed to the bark
scorpion venom, which means that something about the venom was inhibiting the
neuron from reaching its threshold and firing an electrical stimulus that would
travel to the brain of the mouse and cause the perception of pain.
Scientists dove deeper, and decided
to look at the exact ion channels that the venom acted upon. After closer observation,
they found that the sodium gated ion channel, Nav1.8, was inhibited when
exposed to the venom, and underwent a physical change that prevented it from
opening and allowing the influx of sodium ions into the cell that would cause
an action potential. Nav1.8 is involved in the propagation of action potentials
to the central nervous system, where pain is processed. Because the venom
alters the Nav1.8 channel, the pain stimulus never reaches the brain of the
grasshopper mouse, and therefore, when stung the mice feel no pain. Scientists
were curious about the implications of this lack of pain response, and so they
conducted another experiment to determine what the pain response was in mice
after a scorpion sting. They did so by injecting the mice with venom followed
by formalin 15 minutes later. The grasshopper mice that were pretreated with
venom showed a significantly lower pain response to the formalin injection than
the grasshopper mice that were not pretreated with venom. The grasshopper mice
not only have no pain response when stung by the bark scorpion, but also have a
lowered pain response to any stimulus after they have been stung. This seems
maladaptive, because not only do the mice not respond to the dangerous poison
of the scorpion, but their pain response is inhibited for up to 15 minutes
after they are stung. If a something harmful were to happen to the mice after
they were stung by the scorpion, they would not receive the appropriate pain response,
and would therefore not attend to wounds the way they should.
The implications of this research
stretch far beyond grasshopper mice. If we start to understand the mechanisms
behind pain inhibition, and what specific ion channels are involved in the propagation
of pain signals, we can more accurately target pain in humans. Pharmaceuticals
that are more specific could possibly have less harmful side effects, and
target long lasting and chronic pain.
Works Cited
Rowe, Ashlee, et al. “Voltage-Gated Sodium Channel in
Grasshopper Mice Defends Against Bark Scorpion Toxin.” Science AAAS, vol. 342,
13 Oct. 2013.
It is very strange that the scorpion would evolve a venom that targets the Nav1.8 channel. Assuming that this channel has the same functions in the scorpion's other prey, the scorpion basically allows its prey a 15 minute window in which the venom has an adverse effect against the itself. In this window, the prey will, as in the case of the grasshopper mouse, retaliate and potentially kill the scorpion. I would be very interested to see what they find on the evolutionary advantage of this venom, considering it's adverse effects are so detrimental to the scorpion.
ReplyDeleteI found this post really interesting, particularly the implications these experiments have in a pharmaceutical context. You spoke about the inhibition of Nav1.8, which is involved in the propagation of an action potential to the central nervous system. Nav1.7 and Nav1.9 are also found on nociceptors and deal with acute and inflammatory pain responses. If researchers are able to alter these channels specifically I wonder if more targeted drugs could be produced that not only aid in the relief of pain, but can target specific types of pain, such as acute, chronic or inflammatory. With higher specificity it seems that there will be a better chance to avoid the side effects of our current pain medications, such as addiction. There are also some relevant differences between mice and human sodium channels, so perhaps more research should be done that explores how humans would react to such changes in the morphology of specific sodium channels. I attached an article that talks about some of these key differences!
ReplyDeletePlummer, N. W., & Meisler, M. H. (1999). Evolution and diversity of mammalian sodium channel genes. Genomics, 57(2), 323-331.