Lewin Lab

Damir Omerbasic, Ewan St. John Smith, Tetiana Kovalchuk, Jane Reznick

The naked mole rat is an unusual subterranean rodent in many respects. It is the only known poikilothermic mammal (ie. cold blooded), it lives in colonies with an insect-like social structure, and it is also the longest-lived rodent species known (lifetimes in excess of 25 yrs). Interestingly, although this animal has normal acute pain responses it displays no hypersensitivity (so called hyperalgesia) to a variety of inflammatory and chemical stimuli. Moreover, what is particularly striking in the naked mole rat is that it completely lacks a neuronal or behavioral response to acid (Park et al. 2008), which is most unusual in the animalia kingdom (Smith and Lewin 2009). We have proposed a new model for mammalian acid sensing, whereby the ability of acid to excite a neuron is a balance between the activation of ion channels that are gated by acid (ASICs and TRPV1) and the block of voltage-gated sodium channels (NaVs), which are inhibited by acid and crucial for action potential initiation. In naked mole-rats we identified an amino acid variation in NaV1.7, which conveys enhanced sensitivity to acid and thus prevents acid evoking action potentials in naked mole-rat neurons (Smith et al. 2011).

Future work will be focused on discovering the genetic variations underlying other unusual naked mole-rat phenotypes (such as cold-bloodedness and the lack of thermal hyperalgesia), which will in turn aid the understanding of “normal” physiology in other mammals.

Selected publications

1. Park, TJ, Lu Y, Juttner R, Smith ES, Hu J, Brand A, Wetzel C, Milenkovic N, Erdmann B, Heppenstall PA, Laurito CE, Wilson SP & Lewin GR. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber). PLoS biology 6, e13 (2008).
2. Smith, E. St. J. and Lewin, G. R. (2009). Nociceptors: a phylogenetic view. J. Comp. Physiol. A 195, 1089 – 1106.
3. Smith, ES, Blass, GRC, Lewin, GR & Park, TJ. Absence of histamine-induced itch in the African naked mole-rat and "rescue" by Substance P. Mol. Pain, 6:29 (2010)
4. Brand A; Smith ES; Lewin GR; Park TJ Functional neurokinin and NMDA receptor activity in an animal naturally lacking Substance P: the naked mole-rat PLoS ONE 5 (12): e15162 (2010)
5. Smith, E. St. J., Omerbasic, D., Lechner, S. G., Lapatsina, L., Anirudhan, G. and Lewin, G. R. The physiological basis of acid insensitivity in the African naked mole rat. Science 334, 1557 – 1560 (2011)