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Investigation of the presence and antinociceptive function of muscarinic acetylcholine receptors in the African naked mole-rat (Heterocephalus glaber)

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      Abstract

      The present study investigated the cholinergic system in the African naked mole-rat ( Heterocephalus glaber) with focus on the muscarinic acetylcholine receptor subtypes M 1 and M 4. The protein sequences for the subtypes m 1–5 of the naked mole-rat were compared to that of the house mouse ( Mus musculus) using basic local alignment search tool (BLAST). The presence and function of M 1 and M 4 was investigated in vivo, using the formalin test with the muscarinic receptor agonists xanomeline and VU0152100. Spinal cord tissue from the naked mole-rat was used for receptor saturation binding studies with [ 3H]-N-methylscopolamine. The BLAST test revealed 95 % protein sequence homology showing the naked mole-rat to have the genetic potential to express all five muscarinic acetylcholine receptor subtypes. A significant reduction in pain behavior was demonstrated after administration of 8.4 mg/kg in the formalin test. Administration of 50 mg/kg VU0152100 resulted in a non-significant tendency towards antinociception. The antinociceptive effects were reversed by the muscarinic acetylcholine receptor antagonist atropine. Binding studies indicated presence of muscarinic acetylcholine receptors with a radioligand affinity comparable to that reported in mice. In conclusion, muscarinic acetylcholine receptor subtypes are present in the naked mole-rat and contribute to antinociception in the naked mole-rat.

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      Most cited references 40

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      Genome sequencing reveals insights into physiology and longevity of the naked mole rat

      The naked mole rat (NMR, Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal 1 . Although the size of a mouse, its maximum lifespan exceeds 30 years and makes this animal the longest living rodent. NMRs show negligible senescence, no age-related increase in mortality, and high fecundity until death 2 . In addition to delayed aging, NMRs are resistant to both spontaneous cancer and experimentally induced tumorigenesis 3,4 . NMRs pose a challenge to the theories that link aging, cancer and redox homeostasis. Although characterized by significant oxidative stress 5 , the NMR proteome does not show age-related susceptibility to oxidative damage nor increased ubiquitination 6 . NMRs naturally reside in large colonies with a single breeding female, the “queen,” who suppresses the sexual maturity of her subordinates 11 . NMRs also live in full darkness, at low oxygen and high carbon dioxide concentrations 7 , and are unable to sustain thermogenesis 8 nor feel certain types of pain 9,10 . Here we report sequencing and analysis of the NMR genome, which revealed unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness, altered visual function, circadian rhythms and taste sensing, and insensitivity to low oxygen. This information provides insights into NMR’s exceptional longevity and capabilities to live in hostile conditions, in the dark and at low oxygen. The extreme traits of NMR, together with the reported genome and transcriptome information, offer unprecedented opportunities for understanding aging and advancing many other areas of biological and biomedical research.
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        International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors.

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          Opioid-induced hyperalgesia: a qualitative systematic review.

          Opioids are the cornerstone therapy for the treatment of moderate to severe pain. Although common concerns regarding the use of opioids include the potential for detrimental side effects, physical dependence, and addiction, accumulating evidence suggests that opioids may yet cause another problem, often referred to as opioid-induced hyperalgesia. Somewhat paradoxically, opioid therapy aiming at alleviating pain may render patients more sensitive to pain and potentially may aggravate their preexisting pain. This review provides a comprehensive summary of basic and clinical research concerning opioid-induced hyperalgesia, suggests a framework for organizing pertinent information, delineates the status quo of our knowledge, identifies potential clinical implications, and discusses future research directions.
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            Author and article information

            Affiliations
            [ ]Department of Experimental Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamvej 3B, 2200 Copenhagen, Denmark
            [ ]Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark
            [ ]School of Agricultural and Veterinary Sciences, South Eastern Kenya University, P.O. BOX 170-90200, Kitui, Kenya
            Contributors
            +45 30 50 78 13 , klasab@sund.ku.dk
            Journal
            J Comp Physiol A Neuroethol Sens Neural Behav Physiol
            J. Comp. Physiol. A Neuroethol. Sens. Neural. Behav. Physiol
            Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
            Springer Berlin Heidelberg (Berlin/Heidelberg )
            0340-7594
            1432-1351
            31 October 2015
            31 October 2015
            2016
            : 202
            : 7-15
            26520141
            4698283
            1048
            10.1007/s00359-015-1048-x
            © The Author(s) 2015

            Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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            Original Paper
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            © Springer-Verlag Berlin Heidelberg 2016

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