Selective Inflammatory Pain Insensitivity in the African Naked Mole-Rat (Heterocephalus glaber) |
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| Authors: | Thomas J Park Thomas J Park Thomas J Park Thomas J Park Thomas J Park Thomas J Park Thomas J Park Thomas J Park Thomas J Park Thomas J Park |
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| Affiliation: | 1, Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America;2, Department of Anesthesiology, University of Illinois at Chicago, Chicago, Illinois, United States of America;3, Max-Delbrück Center for Molecular Medicine, Berlin, Germany;4, Department of Electron Microscopy, Max-Delbrück Center for Molecular Medicine, Berlin, Germany;5, Klinik für Anaesthesiologie und Operative Intensivmedizin, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany;6, Department of Pharmacology, Physiology, and Neuroscience, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America;University of California San Francisco, United States of America |
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| 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. |
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