ArticleMolecular medicine (Cambridge, Mass.)2012
G protein-coupled receptor kinase 6 acts as a critical regulator of cytokine-induced hyperalgesia by promoting phosphatidylinositol 3-kinase and inhibiting p38 signaling.
Article in Molecular medicine (Cambridge, Mass.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Preclinical Animal Models to Investigate the Role of NaLife (Basel, Switzerland) · 2025Review
- Metabotropic glutamate receptor-8 relieves neonatal maternal separation-induced visceral hypersensitivity in rats by regulating expression of TNF-α.Annals of translational medicine · 2023Article
- The Role of G Protein-Coupled Receptor Kinase 6 Regulation in Inflammation and Pain.International journal of molecular sciences · 2022Review
- G protein-coupled receptor kinases are associated with Alzheimer's disease pathology.Neuropathology and applied neurobiology · 2021Article
- TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice.Neuroscience bulletin · 2021Article
- Characterization of the G protein-coupled receptor kinase 6 promoter reveals a functional CREB binding site.PloS one · 2021Article
- Role of G protein-coupled receptor kinase-6 inPhysiological genomics · 2017Article
- G Protein-Coupled Receptor Kinases in the Inflammatory Response and Signaling.Advances in immunology · 2017Review
- The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments.Journal of neurogastroenterology and motility · 2016Review
- Overexpression of GRK6 attenuates neuropathic pain via suppression of CXCR2 in rat dorsal root ganglion.Molecular pain · 2016Article
- G-protein-coupled receptor kinases in inflammation and disease.Genes and immunity · 2015Review
- The Red Nucleus TNF-α Participates in the Initiation and Maintenance of Neuropathic Pain Through Different Signaling Pathways.Neurochemical research · 2015Article
- Molecular mechanisms underlying β-adrenergic receptor-mediated cross-talk between sympathetic neurons and immune cells.International journal of molecular sciences · 2015Review
- A novel p38 MAPK docking-groove-targeted compound is a potent inhibitor of inflammatory hyperalgesia.The Biochemical journal · 2014Article
- Decreased expression and role of GRK6 in spinal cord of rats after chronic constriction injury.Neurochemical research · 2013Article
- G-protein-coupled receptor kinase 2 and hypertension: molecular insights and pathophysiological mechanisms.High blood pressure & cardiovascular prevention : the official journal of the Italian Society of Hypertension · 2013Review
- MicroRNA-124 as a novel treatment for persistent hyperalgesia.Journal of neuroinflammation · 2012Article
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11 authors at 5 institutions in 4 countries.
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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 was increased compared with WT neurons. In contrast, IL-1β only induced activation of the phosphatidylinositol (PI) 3-kinase/Akt pathway in WT neurons, but not in GRK6⁻/⁻ neurons. In vivo, p38 inhibition attenuated IL-1β- and TNF-α-induced hyperalgesia in both genotypes. Notably, however, whereas PI 3-kinase inhibition enhanced and prolonged hyperalgesia in WT mice, it did not have any effect in GRK6-deficient mice. The capacity of GRK6 to regulate pain responses was also apparent in carrageenan-induced hyperalgesia, since thermal and mechanical hypersensitivity was significantly prolonged in GRK6⁻/⁻ mice. Finally, GRK6 expression was reduced in DRGs of mice with chronic neuropathic or inflammatory pain. Collectively, these findings underline the potential role of GRK6 in pathological pain. We propose the novel concept that GRK6 acts as a kinase that constrains neuronal responsiveness to IL-1β and TNF-α and cytokine-induced hyperalgesia via biased cytokine-induced p38 and PI 3-kinase/Akt activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.