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Transient decrease in nociceptor GRK2 expression produces long-term enhancement in inflammatory pain.

Authors: Ferrari, L F  Bogen, O  Alessandri-Haber, N  Levine, E  Gear, R W  Levine, J D 
Citation: Ferrari LF, etal., Neuroscience. 2012 Oct 11;222:392-403. doi: 10.1016/j.neuroscience.2012.07.004. Epub 2012 Jul 13.
Pubmed: (View Article at PubMed) PMID:22796071
DOI: Full-text: DOI:10.1016/j.neuroscience.2012.07.004

In heterozygous mice, attenuation of G-protein-coupled receptor kinase 2 (GRK2) level in nociceptors is associated with enhanced and prolonged inflammatory hyperalgesia. To further elucidate the role of GRK2 in nociceptor function we reversibly decreased GRK2 expression using intrathecal antisense oligodeoxynucleotide (AS-ODN). GRK2 AS-ODN administration led to an enhanced and prolonged hyperalgesia induced by prostaglandin E(2), epinephrine and carrageenan. Moreover, this effect persisted unattenuated 2weeks after the last dose of antisense, well after GRK2 protein recovered, suggesting that transient attenuation of GRK2 produced neuroplastic changes in nociceptor function. Unlike hyperalgesic priming induced by transient activation of protein kinase C epsilon (PKCe), (Aley et al., 2000; Parada et al., 2003b), the enhanced and prolonged hyperalgesia following attenuation of GRK2 is PKCe- and cytoplasmic polyadenylation element binding protein (CPEB)-independent and is protein kinase A (PKA)- and Src tyrosine kinase (Src)-dependent. Finally, rats treated with GRK2 AS-ODN exhibited enhanced and prolonged hyperalgesia induced by direct activation of second messengers, adenyl cyclase, Epac or PKA, suggesting changes downstream of G-protein-coupled receptors. Because inflammation can produce a decrease in GRK2, such a mechanism could help explain a predilection to develop chronic pain, after resolution of acute inflammation.


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RGD Object Information
RGD ID: 13792780
Created: 2018-09-27
Species: All species
Last Modified: 2018-09-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.