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Item Type: | Article |
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Title: | Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber) |
Creators Name: | Park, T.J., Lu, Y., Jüttner, R., Smith, E.S.J., Hu, J., Brand, A., Wetzel, C., Milenkovic, N., Erdmann, B., Heppenstall, P.A., Laurito, C.E., Wilson, S.P. and Lewin, G.R. |
Abstract: | In all mammals, tissue inflammation leads to pain and behavioral sensitization to thermal and mechanical stimuli called hyperalgesia. We studied pain mechanisms in the African naked mole-rat, an unusual rodent species that lacks pain-related neuropeptides (e.g., substance P) in cutaneous sensory fibers. Naked mole-rats show a unique and remarkable lack of pain-related behaviors to two potent algogens, acid and capsaicin. Furthermore, when exposed to inflammatory insults or known mediators, naked mole-rats do not display thermal hyperalgesia. In contrast, naked mole-rats do display nocifensive behaviors in the formalin test and show mechanical hyperalgesia after inflammation. Using electrophysiology, we showed that primary afferent nociceptors in naked mole-rats are insensitive to acid stimuli, consistent with the animal's lack of acid-induced behavior. Acid transduction by sensory neurons is observed in birds, amphibians, and fish, which suggests that this tranduction mechanism has been selectively disabled in the naked mole-rat in the course of its evolution. In contrast, nociceptors do respond vigorously to capsaicin, and we also show that sensory neurons express a transient receptor potential vanilloid channel-1 ion channel that is capsaicin sensitive. Nevertheless, the activation of capsaicin-sensitive sensory neurons in naked mole-rats does not produce pain-related behavior. We show that capsaicin-sensitive nociceptors in the naked mole-rat are functionally connected to superficial dorsal horn neurons as in mice. However, the same nociceptors are also functionally connected to deep dorsal horn neurons, a connectivity that is rare in mice. The pain biology of the naked mole-rat is unique among mammals, thus the study of pain mechanisms in this unusual species can provide major insights into what constitutes "normal" mammalian nociception. |
Keywords: | Acids, Capsaicin, Hyperalgesia, Inflammation, Afferent Neurons, Nociceptors, Pain, Pain Measurement, Pain Threshold, Posterior Horn Cells, Animals, Mole Rats |
Source: | PLoS Biology |
ISSN: | 1544-9173 |
Publisher: | Public Library of Science |
Volume: | 6 |
Number: | 1 |
Page Range: | e13 |
Date: | 29 January 2008 |
Official Publication: | https://doi.org/10.1371/journal.pbio.0060013 |
PubMed: | View item in PubMed |
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