title: RGS9-2 modulates sensory and mood related symptoms of neuropathic pain.
abstract: The signal transduction modulator Rgs9-2 (Regulator of G protein signaling 9-2) plays a key role in dopaminergic and opioidergic transmission in the striatum. Rgs9-2 is a potent modulator of opiate reward and analgesia, but its role in chronic pain remains unknown. Here, we use the spared nerve injury model (SNI), to evaluate the influence of Rgs9-2 in sensory symptoms, as well as in anxiety and depression-like behaviors observed under neuropathic pain conditions. Our data demonstrate that knockout of the Rgs9 gene reduces the intensity of thermal hyperalgesia and mechanical allodynia the first few days after nerve injury. This small, but significant effect is only observed at early time points after nerve injury, whereas after the first week of SNI, Rgs9 knockout (Rgs9KO) and Rgs9 wildtype (Rgs9WT) mice show similar levels of mechanical allodynia and thermal hyperalgesia. Furthermore, Rgs9-2 deletion exacerbates anxiety and depression like behaviors several weeks after the emergence of the neuropathic pain symptoms. Our findings also reveal a temporal and regional regulation of Rgs9-2 protein expression by neuropathic pain, as Rgs9-2 levels are reduced in the spinal cord a few days after nerve injury, whereas decreased Rgs9-2 levels in the Nucleus Accumbens (NAc) are only observed several weeks after nerve injury. Thus, adaptations in Rgs9-2 activity in the spinal cord and in the NAc may contribute to sensory and affective components of neuropathic pain.
authors.affiliation: University of Crete Faculty of Medicine, Department of Basic Sciences, Heraklion, Crete 71003, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Terzi
authors.affiliation: University of Crete Faculty of Medicine, Department of Basic Sciences, Heraklion, Crete 71003, Greece.
authors.forename: Sevasti
authors.initials: S
authors.lastname: Gaspari
authors.affiliation: University of Crete Faculty of Medicine, Department of Basic Sciences, Heraklion, Crete 71003, 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, Department of Pharmacology and Systems Therapeutics, United States.
authors.forename: Giannina
authors.initials: G
authors.lastname: Descalzi
authors.affiliation: University of Crete Faculty of Medicine, Department of Basic Sciences, Heraklion, Crete 71003, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Mitsi
authors.affiliation: University of Crete Faculty of Medicine, Department of Basic Sciences, Heraklion, Crete 71003, Greece; Icahn School of Medicine at Mount Sinai, Fishberg Department of Neuroscience and Friedman Brain Institute, Department of Pharmacology and Systems Therapeutics, United States. Electronic address: venetia.zachariou@mssm.edu.
authors.forename: Venetia
authors.initials: V
authors.lastname: Zachariou
mesh_terms: D000339:Affect / Q000502:physiology; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D015153:Blotting, Western; D003863:Depression / Q000503:physiopathology; D005260:Female; D006930:Hyperalgesia / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000503:physiopathology* / Q000523:psychology; D009714:Nucleus Accumbens / Q000737:chemistry; D020710:RGS Proteins / Q000032:analysis / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry
chemical_list: D020710:RGS Proteins; C116925:regulator of g-protein signaling 9
keywords: Chronic pain; Forced swim; Mechanical allodynia; Nociception; Signal transduction; Spared nerve injury; Thermal hyperalgesia