Why the Highveld Mole Rat Does Not Sense Pain

By Nicole Zhao ‘20 

Naked Mole-rat
Figure 1. Heterocephalus glaber, otherwise known as the naked mole rat, is insensitive to hydrogen chloride or capsaicin.

Plants and insects alike often use algogens, noxious substances, as defensive weapons against predators (1). Predators, such as humans, detect these algogens via the receptors of nociceptive sensory neurons and are warned to back off(2). It has previously been shown that Heterocephalus glaber, otherwise known as the naked mole rat, shows no pain behavior when exposed to hydrogen chloride and capsaicin, two powerful algogens (3). In a new study conducted by researchers from the Max Delbrück Center for Molecular Medicine in Berlin, Germany, nine African rodent species related to the naked mole-rat were exposed to different algogens to determine if they shared this extraordinary trait (1).

It was found that while some species were insensitive to hydrogen chloride or capsaicin, or both, most species exhibited robust pain behaviors in response to allyl isothiocyanate (AITC) (1). AITC is the active ingredient in mustard oil and produces pain by actively damaging proteins in cells (4). While initial experiments injected all test subjects with 0.75% solution of AITC,  one particular species of highveld mole rat did not even flinch when injected with pure AITC. Researchers then compared the pain-signaling neurons of all nine species in the study to explore why the highveld mole rat does not feel the pain when injected with AITC. It was found that the neurons in highveld mole rat contained a unique ion-channel called NALCN (1). This sodium ion channel is very leaky, making it hard to excite the neurons. Further investigations revealed that the highveld mole rats evolved with the ability to resist AITC pain due to Natal droptail ants that are part of their ecosystem (1). Natal droptail ants contain venom that contains formic acid  and is similar AITC. Therefore, the highveld mole rat has developed such a high pain insensitivity to AITC because they had already adapted to the venom of the ants that are in their habitat.This discovery is yet another example of how two species can exert evolutionary forces on each other. As a result, the highveld mole rat can live where other mole rats cannot. Furthermore, the discovery of the NALCN leaky sodium channels provides a potential mechanism for drugs to modulate their activity to treat pain in humans. 

References:

  1. O. Eigenbrod, et al., Rapid molecular evolution of pain insensitivity in multiple african rodents. Science 364, 852-859 (2019). doi: 10.1126/science.aau0236. 
  2. E. Smith. Nociceptors: a phylogenetic view. Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology 195, 1089–1106 (2009). doi: 10.1007/s00359-009-0482-z. 
  3. E. Smith. The molecular basis of acid insensitivity in the african naked mole-rat. Science 334, 1557-60 (2011). doi: 10.1126/science.1213760. 
  4. S. Jordt, et al., Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427, 260-5 (2004). doi: 10.1038/nature02282. 
  5. Image retrieved from: https://www.flickr.com/photos/timevanson/29083512364
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