Research Article of Science 364, pg. 852–859 (2019)
Noxious substances, called algogens, cause pain and are used as defensive weapons by plants
and stinging insects. We identified four previously unknown instances of algogen-insensitivity
by screening eight African rodent species related to the naked mole-rat with the painful
substances capsaicin, acid (hydrogen chloride, pH 3.5), and allyl isothiocyanate (AITC). Using
RNA sequencing, we traced the emergence of sequence variants in transduction channels,
like transient receptor potential channel TRPA1 and voltage-gated sodium channel Na v 1.7, that
accompany algogen insensitivity. In addition, the AITC-insensitive highveld mole-rat
exhibited overexpression of the leak channel NALCN (sodium leak channel, nonselective),
ablating AITC detection by nociceptors. These molecular changes likely rendered highveld
mole-rats immune to the stings of the Natal droptail ant. Our study reveals how evolution can be
used as a discovery tool to find molecular mechanisms that shut down pain.