Rapid molecular evolution of pain insensitivity in multiple African rodents

Science. 2019 May 31;364(6443):852-859. doi: 10.1126/science.aau0236.


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 Nav1.7, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Capsaicin / pharmacology
  • Evolution, Molecular*
  • Hydrochloric Acid / pharmacology
  • Insect Bites and Stings / genetics
  • Insect Bites and Stings / immunology
  • Isothiocyanates / pharmacology
  • Mole Rats / genetics
  • Mole Rats / immunology
  • Mole Rats / physiology*
  • NAV1.7 Voltage-Gated Sodium Channel / genetics*
  • Nociceptive Pain / chemically induced
  • Nociceptive Pain / genetics*
  • Nociceptors / drug effects
  • Nociceptors / physiology
  • Pain Threshold*
  • Protein Conformation
  • Sequence Analysis, RNA
  • Species Specificity
  • TRPA1 Cation Channel / chemistry
  • TRPA1 Cation Channel / genetics*


  • Isothiocyanates
  • NAV1.7 Voltage-Gated Sodium Channel
  • TRPA1 Cation Channel
  • allyl isothiocyanate
  • Hydrochloric Acid
  • Capsaicin