title: RGS9-2 Modulates Responses to Oxycodone in Pain-Free and Chronic Pain States.
abstract: Regulator of G-protein signaling 9-2 (RGS9-2) is a striatal-enriched signal-transduction modulator known to have a critical role in the development of addiction-related behaviors following exposure to psychostimulants or opioids. RGS9-2 controls the function of several G-protein-coupled receptors, including dopamine receptor and mu opioid receptor (MOR). We previously showed that RGS9-2 complexes negatively control morphine analgesia, and promote the development of morphine tolerance. In contrast, RGS9-2 positively modulates the actions of other opioid analgesics, such as fentanyl and methadone. Here we investigate the role of RGS9-2 in regulating responses to oxycodone, an MOR agonist prescribed for the treatment of severe pain conditions that has addictive properties. Using mice lacking the Rgs9 gene (RGS9KO), we demonstrate that RGS9-2 positively regulates the rewarding effects of oxycodone in pain-free states, and in a model of neuropathic pain. Furthermore, although RGS9-2 does not affect the analgesic efficacy of oxycodone or the expression of physical withdrawal, it opposes the development of oxycodone tolerance, in both acute pain and chronic neuropathic pain models. Taken together, these data provide new information on the signal-transduction mechanisms that modulate the rewarding and analgesic actions of oxycodone.
authors.affiliation: Icahn School of Medicine at Mount Sinai, Fishberg Department of Neuroscience and Friedman Brain Institute, New York, NY, USA.|University of Crete Faculty of Medicine, Department of Basic Sciences, Heraklion, Greece.
authors.forename: Sevasti
authors.initials: S
authors.lastname: Gaspari
authors.affiliation: Icahn School of Medicine at Mount Sinai, Fishberg Department of Neuroscience and Friedman Brain Institute, New York, NY, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cogliani
authors.affiliation: University of Crete Faculty of Medicine, Department of Basic Sciences, Heraklion, Greece.
authors.forename: Lefteris
authors.initials: L
authors.lastname: Manouras
authors.affiliation: Icahn School of Medicine at Mount Sinai, Fishberg Department of Neuroscience and Friedman Brain Institute, New York, NY, USA.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Anderson
authors.affiliation: Icahn School of Medicine at Mount Sinai, Fishberg Department of Neuroscience and Friedman Brain Institute, New York, NY, USA.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Mitsi
authors.affiliation: Icahn School of Medicine at Mount Sinai, Fishberg Department of Neuroscience and Friedman Brain Institute, New York, NY, USA.
authors.forename: Kleopatra
authors.initials: K
authors.lastname: Avrampou
authors.affiliation: Icahn School of Medicine at Mount Sinai, Fishberg Department of Neuroscience and Friedman Brain Institute, New York, NY, USA.
authors.forename: Fiona B
authors.initials: FB
authors.lastname: Carr
authors.affiliation: Icahn School of Medicine at Mount Sinai, Fishberg Department of Neuroscience and Friedman Brain Institute, New York, NY, USA.
authors.forename: Venetia
authors.initials: V
authors.lastname: Zachariou
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010098:Oxycodone / Q000494:pharmacology / Q000627:therapeutic use*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*; D020710:RGS Proteins / Q000172:deficiency*; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D010098:Oxycodone