Figure 6

GRK6 mRNA levels in DRGs during chronic neuropathic and inflammatory pain. (A) The sensitivity to mechanical stimulation was determined in sham-operated mice (n = 8) or mice subjected to unilateral L5 SNT 4 wks after surgery (n = 10). (B) GRK6 mRNA levels in DRGs innervating the contralateral (-C) or ipsilateral (-I) side of sham-operated (n = 4) and L5 SNL (n = 5) mice 4 wks after surgery. The sensitivity to thermal stimulation was determined after intraplantar injection of vehicle (n = 5) or carrageenan (n = 5) (C), and 6 d later, DRG GRK6 mRNA expression levels were determined (n = 5) (D). GRK6 mRNA expression levels were corrected for GAPDH and β-actin mRNA expression levels. All data are expressed as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001. (E) In WT mice, IL-1β induces activation of the p38 and PI 3-kinase/Akt signaling cascade leading to transient hyperalgesia. The activation of p38 promotes hyperalgesia, whereas activation of the PI 3-kinase/Akt signaling cascade constrains hyperalgesia. Loss of GRK6 enhances p38 activity in sensory neurons, whereas activation of the PI 3-kinase/Akt pathway is attenuated, ultimately leading to enhanced and prolonged cytokine-induced hyperalgesia.