title: RGS9-2 modulates nociceptive behaviour and opioid-mediated synaptic transmission in the spinal dorsal horn.
abstract: The regulator of G protein signaling 9-2 (RGS9-2) is a constituent of G protein-coupled receptor (GPCR) macromolecular complexes with a major role in regulation of GPCR activity in the central nervous system. Previous in situ hybridization and Western blot studies revealed that RGS9-2 is expressed in the superficial dorsal horn of the spinal cord. In the present study, we monitored tail withdrawal latencies to noxious thermal stimuli and performed in vitro whole-cell patch clamp electrophysiological recordings from neurons in lamina II of the spinal dorsal horn to examine the role of RGS9-2 in the dorsal horn of the spinal cord in nociceptive behaviours and opiate mediated modulation of synaptic transmission. Our findings obtained from RGS9 knockout mice indicate that the lack of RGS9-2 protein decreases sensitivity to thermal stimuli and to the analgesic actions of morphine in the tail immersion paradigm. This modulatory role of RGS9-2 on opiate-mediated responses was further supported by electrophysiological studies showing that hyperpolarization of neurons in lamina II of the spinal dorsal horn evoked by application of DAMGO ([d-Ala2, N-MePhe4, Gly-ol]-enkephalin, a mu opioid receptor agonist) was diminished in RGS9 knockout mice. The results indicate that RGS9-2 enhances the effect of morphine and may play a crucial role in opiate-mediated analgesic mechanisms at the level of the spinal cord.
authors: Department of Basic Science, University of Crete, Faculty of Medicine, Heraklion, Crete 71003, Greece.
authors: Maria Martha
authors: MM
authors: Papachatzaki
authors: Zsófia
authors: Z
authors: Antal
authors: Dimitra
authors: D
authors: Terzi
authors: Péter
authors: P
authors: Szücs
authors: Venetia
authors: V
authors: Zachariou
authors: Miklós
authors: M
authors: Antal
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D020710:RGS Proteins; D017450:Receptors, Opioid, mu; C116925:regulator of g-protein signaling 9; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine