title: Enhancement of morphine analgesia and prevention of morphine tolerance by downregulation of β-arrestin 2 with antigene RNAs in mice.
abstract: β-arrestin 2, a regulatory molecule of G protein-coupled receptor, has been proved to play an important role in regulating functions of mu opioid receptor. Changes of β-arrestin 2 expression might affect the function of mu opioid receptors and the effect of its agonists. In this study, antigene RNAs (agRNAs), which could selectively target gene transcription start sites and potently inhibit gene expression, were used to downregulate the expression of β-arrestin 2 to investigate its effects on morphine analgesia and tolerance in mice. After intracerebroventricular administration of recombinant lentivirus encoding β-arrestin 2 agRNAs to the mice, β-arrestin 2 expression was significantly decreased for more than 3 weeks. Mice treated with β-arrestin 2 agRNAs showed enhanced analgesic effects in response to morphine and failed to develop antinociceptive tolerance. These results suggest that inhibition of β-arrestin 2 in the brain with specific agRNAs can improve morphine efficacy, and consequently provide us a useful strategy for treatment of chronic intractable pain and morphine tolerance in vivo.
authors.affiliation: Department of Anesthesiology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Huilian
authors.initials: H
authors.lastname: Bu
authors.forename: Xijiang
authors.initials: X
authors.lastname: Liu
authors.forename: Xuebi
authors.initials: X
authors.lastname: Tian
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004361:Drug Tolerance / Q000502:physiology; D005822:Genetic Vectors / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy*; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects; D012313:RNA / Q000276:immunology*; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: D000701:Analgesics, Opioid; D000906:Antibodies; C000605258:Arrb2 protein, mouse; D019390:Arrestins; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D049452:Green Fluorescent Proteins; D012313:RNA; D009020:Morphine
keywords: analgesia; gene silencing; morphine; tolerance; β-arrestin