Independent evolution of pain insensitivity in African mole-rats: origins and mechanisms

Ewan St John Smith,Gary R Lewin,Thomas J Park

doi:10.1007/s00359-020-01414-w

Abstract

The naked mole-rat (Heterocephalus glaber) is famous for its longevity and unusual physiology. This eusocial species that lives in highly ordered and hierarchical colonies with a single breeding queen, also discovered secrets enabling somewhat pain-free living around 20 million years ago. Unlike most mammals, naked mole-rats do not feel the burn of chili pepper’s active ingredient, capsaicin, nor the sting of acid. Indeed, by accumulating mutations in genes encoding proteins that are only now being exploited as targets for new pain therapies (the nerve growth factor receptor TrkA and voltage-gated sodium channel, NaV1.7), this species mastered the art of analgesia before humans evolved. Recently, we have identified pain insensitivity as a trait shared by several closely related African mole-rat species. One of these African mole-rats, the Highveld mole-rat (Cryptomys hottentotus pretoriae), is uniquely completely impervious and pain free when confronted with electrophilic compounds that activate the TRPA1 ion channel. The Highveld mole-rat has evolved a biophysical mechanism to shut down the activation of sensory neurons that drive pain. In this review, we will show how mole-rats have evolved pain insensitivity as well as discussing what the proximate factors may have been that led to the evolution of pain-free traits.

Highlights

Pain is so central to our personal experience that we as humans assume that all non-human animals experience pain in a similar way to ourselves
In 2008, we discovered that capsaicin was not a universal irritant in mammals as our studies on the nociceptive system of the naked mole-rat (Heterocephalus glaber) revealed that this unusual subterranean mammal was completely insensitive to capsaicin (Park et al 2008)
We showed that naked mole-rats show robust nocifensive behavior after hindpaw injection of Allyl isothiocyanate (AITC) (Eigenbrod et al 2019)

Summary

Introduction

Pain is so central to our personal experience that we as humans assume that all non-human animals experience pain in a similar way to ourselves. The first detailed examination of sensory anatomy in the naked mole-rat demonstrated that the skin of this largely hairless species is innervated by both myelinated and unmyelinated fibers (Park et al 2003).

Results

Conclusion