title: Gq rather than G11 preferentially mediates nociceptor sensitization.
abstract: BACKGROUND
  The G(q/11)-protein signaling mechanism is essential throughout the nervous system, but little is known about the contribution of the individual G-protein GPCR signaling branches towards nociceptor activation and their specific role on nociceptor sensitization. We aimed to unravel the contribution of the G(q/11)-signaling pathway towards nociceptor activation via a variety of classical inflammatory mediators signalling via different G-protein GPCRs and investigated the specific contribution of the individual G(q) and G(11) G-Proteins in nociceptors.
  
  
  RESULTS
  Using different transgenic mouse lines, lacking Gα(q), Gα(11) or both α-subunit of the G-proteins in primary nociceptive neurons, we analyzed the mechanical- and heat-sensitivity upon application of different GPCR-agonists that are known to play an important role under inflammatory conditions (e.g. ATP, Glutamate, Serotonin etc.). We found that the G(q/11)-GPCR signaling branch constitutes a primary role in the manifestation of mechanical allodynia and a minor role in the development of thermal hyperalgesia. Moreover, with respect to the mediators used here, the G(q)-protein is the principle G-protein among the G(q/11)-protein family in nociceptive neurons leading to nociceptor sensitization.
  
  
  CONCLUSIONS
  Our results demonstrate that the G(q/11) signaling branch plays a primary role in nociceptor sensitization upon stimulation with classical GPCR ligands, contributing primarily towards the development of mechanically allodynia. Moreover, the deletion of the individual G-proteins led to the finding that the G(q)-protein dominates the signalling machinery of the G(q/11) family of G-proteins in nociceptive neurons.
authors.forename: Laura Nikita
authors.initials: LN
authors.lastname: Wirotanseng
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
authors.affiliation: Pharmacology Institut, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, D-69120, Germany. anke.tappe-theodor@pharma.uni-heidelberg.de.
authors.forename: Anke
authors.initials: A
authors.lastname: Tappe-Theodor
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
chemical_list: D008246:Lysophospholipids; D018377:Neurotransmitter Agents; C060506:sphingosine 1-phosphate; D012701:Serotonin; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D013917:Thrombin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D013110:Sphingosine; D001920:Bradykinin; D014544:Uridine Triphosphate