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Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber)

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Item Type:Article
Title:Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber)
Creators Name:Park, T.J. and Lu, Y. and Jüttner, R. and Smith, E.S.J. and Hu, J. and Brand, A. and Wetzel, C. and Milenkovic, N. and Erdmann, B. and Heppenstall, P.A. and Laurito, C.E. and 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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