Scientists have discovered why grasshopper mice are immune to the pain caused by bark scorpion venom. Source: American Society of Mammalogists.
The ability to sense pain is an important evolutionary adaption— it usually calls attention to some sort of tissue damage. Thus, several animals have developed defense mechanisms such as venoms or stings that exploit pain sensitivity in predators. These defense toxins function by stimulating specific pain sensing neurons that are part of the Central Nervous System (CNS).
It is quite rare to see animals that have developed immunity rather than heightened sensitivity to pain, because the sensation of pain often prevents detrimental behavior. However, the grasshopper mouse (O. torridus) seems to have developed immunity to both the lethality and the pain of a bark scorpion’s (C. sculpturatus) venom.
Scientists from the University of Texas at Austin, Indiana University School of Medicine, Sam Houston State University, and Josephine Bay Paul Center for Comparative Molecular Biology and Evolution have discovered exactly why the grasshopper mouse is immune to the pain.
The researchers used standard house mice (Mus musculus) as their control specimens, and used saline and formalin as their controls. First, the researchers gave saline injections to both species of mice in their hind paws. They then counted the number of times each species licked their hind paws in an attempt to soothe any discomfort. The number of paw licks per second was fairly similar for both species. However, when the researchers injected non-lethal doses of bark scorpion venom into both species’ hind paws, Mus musculus’ licking rate increased from roughly 15 licks per second (saline) to almost 220 licks per second while O. torridus’ licking rate decreased from roughly 26 licks per second (saline) to 9 licks per second.
In order to determine whether or not grasshopper mice are uniquely resistant to pain caused by bark scorpion venom, researchers also injected formalin into both species. The difference in rate of paw licking between these two species was not nearly as large as when venom was injected. Thus, grasshopper mice found formalin to be the most painful, saline the second most painful, and venom the third most painful. Normal house mice found venom the most painful, formalin the second most painful, and saline the least painful.
Acute pain signals are “transmitted to the CNS mainly by two voltage-gated sodium channels, tetrodotoxin-sensitive Nav1.7 and tetrodotoxin-resistant Nav1.8” (1). Tetrodotoxin is a common poison that animals such as the bark scorpion release. Voltage-gated sodium channels are protein channels on neurons that allow for the build up of charge, ultimately causing an action potential.
The researchers discovered that grasshopper mice’s immunity to pain caused by bark scorpion venom is derived from their unique neuronal ion channels. Instead of inducing action potentials in pain-sensing neurons, the venom blocks the sodium channel in the Nav1.8 sodium channel. Nav1.7 stimulates the action potential while Nav1.8 allows it to continue. However, if Nav1.8 is blocked as it is in grasshopper mice, the pain sensation cannot be sustained.
Upon delving deeper into the mechanisms of Nav1.8 blockage, the researchers discovered that Nav1.8 is fundamentally different in grasshopper mice. In grasshopper mice, two amino acids are different in the Nav1.8 sodium channel than the Nav1.8 in M. musculus.
These findings have important implications in regards to pain management. Understanding the grasshopper mouse’s immunity to pain from bark scorpion venom “could serve as the basis for designing highly selective, nonaddictive analgesics” (1).
References:
1. A. H. Rowe et al., Science. 342, 441-446 (2013).
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