Garza Carbajal, Anibal, Ebersberger, Andrea, Thiel, Alina, Ferrari, Luiz, Acuna, Jeremy, Brosig, Stephanie, Isensee, Joerg, Moeller, Katharina, Siobal, Maike, Rose-John, Stefan ORCID: 0000-0002-7519-3279, Levine, Jon, Schaible, Hans-Georg and Hucho, Tim . Oncostatin M induces hyperalgesic priming and amplifies signaling of cAMP to ERK by RapGEF2 and PKA. J. Neurochem.. HOBOKEN: WILEY. ISSN 1471-4159

Full text not available from this repository.

Abstract

Hyperalgesic priming is characterized by enhanced nociceptor sensitization by pronociceptive mediators, prototypically PGE(2). Priming has gained interest as a mechanism underlying the transition to chronic pain. Which stimuli induce priming and what cellular mechanisms are employed remains incompletely understood. In adult male rats, we present the cytokine OncostatinM(OSM), a member of the IL-6 family, as an inducer of priming by a novel mechanism. We used a high content microscopy based approach to quantify the activation of endogenous PKA-II and ERK of thousands sensory neurons in culture. Incubation with OSM increased and prolonged ERK activation by agents that increase cAMP production such as PGE(2), forskolin, and cAMP analogs. These changes were specific to IB4/CaMKII alpha positive neurons, required protein translation, and increased cAMP-to-ERK signaling. In both, control and OSM-treated neurons, cAMP/ERK signaling involved RapGEF2 and PKA but not Epac. Similar enhancement of cAMP-to-ERK signaling could be induced by GDNF, which acts mostly on IB4/CaMKII alpha-positive neurons, but not by NGF, which acts mostly on IB4/CaMKII alpha-negative neurons. In vitro, OSM pretreatment rendered baseline TTX-R currents ERK-dependent and switched forskolin-increased currents from partial to full ERK-dependence in small/medium sized neurons. In summary, priming induced by OSM uses a novel mechanism to enhance and prolong coupling of cAMP/PKA to ERK1/2 signaling without changing the overall pathway structure.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Garza Carbajal, AnibalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebersberger, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiel, AlinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferrari, LuizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Acuna, JeremyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brosig, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isensee, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moeller, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siobal, MaikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rose-John, StefanUNSPECIFIEDorcid.org/0000-0002-7519-3279UNSPECIFIED
Levine, JonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaible, Hans-GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hucho, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-318817
DOI: 10.1111/jnc.15172
Journal or Publication Title: J. Neurochem.
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1471-4159
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROTEIN-KINASE-A; CHRONIC PAIN; NOCICEPTIVE PLASTICITY; INFLAMMATORY PAIN; GENE-EXPRESSION; SENSORY NEURONS; SOLUBLE IL-6; ACTIVATION; SENSITIZATION; MECHANISMSMultiple languages
Biochemistry & Molecular Biology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/31881

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item