Gq Rather Than G11 Preferentially Mediates Nociceptor Sensitization

Overview

Journal Mol Pain

Date 2013 Oct 26

PMID 24156378

Citations 6

Authors

Laura Nikita Wirotanseng

Rohini Kuner

Anke Tappe-Theodor

Affiliations

Soon will be listed here.

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.

Findings: 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.

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