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The Somatosensory World of the African Naked Mole-Rat

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The Extraordinary Biology of the Naked Mole-Rat

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1319))

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. In this chapter we will show how African 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.

figure a

Photo Credit: Thomas Park

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Abbreviations

AITC:

Allyl isothiocyanate

ASIC :

Acid-sensing ion channel

CGRP :

Calcitonin gene-related peptide

CIP :

Congenital insensitivity to pain

DRG :

Dorsal root ganglia

GPCR :

G-protein coupled receptor

NALCN :

Sodium leak channel non-selective protein

NaV:

voltage-gated sodium channel

NGF:

Nerve growth factor

NK1R :

neurokinin-1 receptor

PRDM12 :

PRDI-BF1 and RIZ homology domain- containing protein 12

SP :

Substance P

TG:

Trigeminal ganglion

TRPA1 :

transient receptor potential cation channel subfamily A member 1 channel

TRPV1 :

transient receptor potential vanilloid 1 channel

TWIK1 :

Two pore-domain Weakly Inward rectifying K+ channel

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Acknowledgements

The work in the authors laboratories has been supported by the following agencies: ERC advanced grants to GRL (AdG 789128 and AdG 294678), a National Science Foundation (grant 1655494) to T.J.P. and a CRUK Grant (C56829/A22053) to ESS.

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Authors and Affiliations

  1. Molecular Physiology of Somatic Sensation, Max Delbrück Center for Molecular Medicine, Berlin, Germany

    Gary R. Lewin & Karlien Debus

  2. Department of Pharmacology, University of Cambridge, Cambridge, UK

    Ewan St. J. Smith

  3. Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany

    Jane Reznick

  4. Max Planck Institute for Brain Research, Max-von-Laue-Straße 4, Frankfurt am Main, Germany

    Alison J. Barker

  5. Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA

    Thomas J. Park

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  1. Gary R. Lewin
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Correspondence to Gary R. Lewin .

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  1. Calico Life Sciences LLC, South San Francisco, CA, USA

    Rochelle Buffenstein

  2. Laboratory of Integrative NeuroscienceDepartment of Biological Sciences, University of Illinois at Chicago, Chicago, IL, USA

    Thomas J. Park

  3. Department of Psychology, University of Toronto Mississauga, Mississauga, ON, Canada

    Melissa M. Holmes

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Lewin, G.R., Smith, E.S.J., Reznick, J., Debus, K., Barker, A.J., Park, T.J. (2021). The Somatosensory World of the African Naked Mole-Rat. In: Buffenstein, R., Park, T.J., Holmes, M.M. (eds) The Extraordinary Biology of the Naked Mole-Rat. Advances in Experimental Medicine and Biology, vol 1319. Springer, Cham. https://doi.org/10.1007/978-3-030-65943-1_7

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