Synergistic analgesic effects between neuronostatin and morphine at the supraspinal level |
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| Institution: | 1. Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China;2. School of Pharmacy, Lanzhou University, 222 Tian Shui South Road, Lanzhou, 730000, PR China;1. Laboratory of Natural Products Analysis, Department of Environmental Analysis, Institute for Environmental and Human Health Protection, Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-308, Poland;2. Department of Invertebrate Zoology and Parasitology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland;3. Department of Animal Physiology and Development, Adam Mickiewicz University, Umultowska 89, 61-614 Poznan, Poland;1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA;2. Division of General Internal Medicine, Johns Hopkins School of Medicine, 1830 E. Monument Street, Baltimore, MD, 21205, USA;3. Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA;1. Department of Anesthesiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, China;2. Yixing Clinical College, Medical College of Yangzhou University, Yixing, Jiangsu, China;3. School of Experience Industry, Anhui Polytechnic University, Wuhu, Anhui, China;4. Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu, China;5. Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China;1. Diabetes and Obesity Research Laboratory, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain;2. Department of Endocrinology and Nutrition, Hospital Clínic, School of Medicine, University of Barcelona, 08036 Barcelona, Spain;3. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain;4. Laboratory of Metabolism, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland;5. Institute for Research in Biomedicine (IRB Barcelona), 08028 Barcelona, Spain;6. Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain;7. CNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3060-197 Cantanhede, Portugal;8. Department of Neurochemistry and Neuropharmacology, IIBB–CSIC–IDIBAPS, 08036 Barcelona, Spain;9. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), 28029 Madrid, Spain |
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| Abstract: | Neuronostatin, a 13-amino acid peptide, is encoded in the somatostatin pro-hormone. I.c.v. administration of neuronostatin produces a significant antinociceptive effect in the mouse tail-flick test, which is mediated by endogenous opioid receptor. However, the direct functional interaction between morphine and neuronostatin has not been characterized. In the present study, effect of neuronostatin on morphine analgesia was investigated in the tail-flick test. Our findings showed that i.c.v. administration of neuronostatin (0.3 nmol/mouse i.c.v.) significantly enhanced the antinociceptive effect of morphine (2.5, 5 or 10 μg/kg) at the supraspinal level. Results of antagonism experiments suggested that the synergistic analgesia induced by morphine and neuronostatin was mediated by μ- and к-opioid receptors not δ-opioid receptor. In conclusion, there may be a cascade amplification phenomenon when morphine and neuronostatin were co-administered in acute pain model. The above results provide evidence for the potential use of neuronostatin in combination with morphine to control pain and addiction. |
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| Keywords: | Neuronostatin Morphine Opioid receptors Synergistic analgesia Mice |
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