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The naked mole-rat has evolved to survive and thrive in a low oxygen, high carbon dioxide environment that would be deadly to humans and most other mammals. The naked mole-rat\u2019s lifestyle is unusual in that this species combines subterranean living and living in large, social groups of up to 300\u2009+\u2009individuals. Many respiring animals in a closed environment can lead to depletion of oxygen (hypoxia) and accumulation of carbon dioxide (hypercapnia). Naked mole-rats display a variety of physiological traits that negate the adverse effects of living in this atmosphere. For hypoxia tolerance, naked mole-rats have a low resting metabolism, high affinity hemoglobin, intrinsic brain tolerance, the ability to use fructose for anaerobic glycolysis, and the ability to enter a low energy, suspended animation-like state. For hypercapnia tolerance, these animals have a mutation in a voltage gated sodium channel that effectively eliminates neuronal responses to tissue acidosis. In other mammals, acidosis from exposure to high concentrations of carbon dioxide induces pain and pulmonary edema. Understanding these mechanisms of extreme physiology is not only inherently interesting, but it may lead to biomedical breakthroughs in research on heart attacks, strokes, and pain pathologies.<\/jats:p>","DOI":"10.1007\/s10974-022-09623-3","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T18:02:45Z","timestamp":1658253765000},"page":"61-72","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Extreme Physiology Extreme Tolerance to Hypoxia, Hypercapnia, and Pain in the Naked Mole-Rat"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2447-2948","authenticated-orcid":false,"given":"Thomas J.","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Reznick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"issue":"1","key":"9623_CR1","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/0304-3959(92)90187-G","volume":"49","author":"F Anton","year":"1992","unstructured":"Anton F, Euchner I, Handwerker HO (1992) Psychophysical examination of pain induced by defined CO2 pulses applied to the nasal mucosa. 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