G protein-coupled receptor kinase 6 acts as a critical regulator of cytokine-induced hyperalgesia by promoting phosphatidylinositol 3-kinase and inhibiting p38 signaling.

ABSTRACT: The molecular mechanisms determining magnitude and duration of inflammatory pain are still unclear. We assessed the contribution of G protein-coupled receptor kinase (GRK)-6 to inflammatory hyperalgesia in mice. We showed that GRK6 is a critical regulator of severity and duration of cytokine-induced hyperalgesia. In GRK6⁻/⁻ mice, a significantly lower dose (100 times lower) of intraplantar interleukin (IL)-1β was sufficient to induce hyperalgesia compared with wild-type (WT) mice. In addition, IL-1β hyperalgesia lasted much longer in GRK6⁻/⁻ mice than in WT mice (8 d in GRK6⁻/⁻ versus 6 h in WT mice). Tumor necrosis factor (TNF)-α-induced hyperalgesia was also enhanced and prolonged in GRK6⁻/⁻ mice. In vitro, IL-1β-induced p38 phosphorylation in GRK6⁻/⁻ dorsal root ganglion (DRG) neurons w

SUBMITTER: Eijkelkamp N 

PROVIDER: S-EPMC3388142 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature