title: Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber).
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.
authors.affiliation: Laboratory of Integrative Neuroscience, Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, United States of America. tpark@uic.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Park
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: René
authors.initials: R
authors.lastname: Jüttner
authors.forename: Ewan St J
authors.initials: ES
authors.lastname: Smith
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Antje
authors.initials: A
authors.lastname: Brand
authors.forename: Christiane
authors.initials: C
authors.lastname: Wetzel
authors.forename: Nevena
authors.initials: N
authors.lastname: Milenkovic
authors.forename: Bettina
authors.initials: B
authors.lastname: Erdmann
authors.forename: Paul A
authors.initials: PA
authors.lastname: Heppenstall
authors.forename: Charles E
authors.initials: CE
authors.lastname: Laurito
authors.forename: Steven P
authors.initials: SP
authors.lastname: Wilson
authors.forename: Gary R
authors.initials: GR
authors.lastname: Lewin
mesh_terms: D000143:Acids / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced*; D007249:Inflammation; D019577:Mole Rats; D009475:Neurons, Afferent; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology* / Q000523:psychology; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D020671:Posterior Horn Cells
chemical_list: D000143:Acids; D002211:Capsaicin