TY  - JOUR
A1  - Quarta, Serena
A1  - Vogl, Christian
A1  - Constantin, Cristina E.
A1  - Üçeyler, Nurcan
A1  - Sommer, Claudia
A1  - Kress, Michaela
T1  - Genetic evidence for an essential role of neuronally expressed IL-6 signal transducer gp130 in the induction and maintenance of experimentally induced mechanical hypersensitivity \(in\) \(vivo\) and \(in\) \(vitro\)
JF  - Molecular Pain
N2  - Tenderness and mechanical allodynia are key symptoms of malignant tumor, inflammation and neuropathy. The proinflammatory cytokine interleukin-6 (IL-6) is causally involved in all three pathologies. IL-6 not only regulates innate immunity and inflammation but also causes nociceptor sensitization and hyperalgesia. In general and in most cell types including immune cells and sensory neurons, IL-6 binds soluble mu receptor subunits which heteromerizes with membrane bound IL-6 signal transducer gp130. In the present study, we used a conditional knock-out strategy to investigate the importance of signal transducer gp130 expressed in C nociceptors for the generation and maintenance of mechanical hypersensitivity. Nociceptors were sensitized to mechanical stimuli by experimental tumor and this nociceptor sensitization was preserved at later stages of the pathology in control mice. However, in mice with a conditional deletion of gp130 in Nav1.8 expressing nociceptors mechanical hypersensitivity by experimental tumor, nerve injury or inflammation recovery was not preserved in the maintenance phase and nociceptors exhibited normal mechanical thresholds comparable to untreated mice. Together, the results argue for IL-6 signal transducer gp130 as an essential prerequisite in nociceptors for long-term mechanical hypersensitivity associated with cancer, inflammation and nerve injury.
KW  - Leukemia Inhibitory Factor
KW  - Mediated Inflammatory Hyperalgesia
KW  - Necrosis-factor-Alpha
KW  - Oncostatin-M-Receptor
KW  - Rat Sensory Neurons
KW  - Rheumatoid-Arthritis
KW  - Interleukin-6-Deficient mice
KW  - Peripheral Inflammation
KW  - Thermal Hyperalgesia
KW  - Heat Hyperalgesia
KW  - proinflammatory cytokine
KW  - Interleukin-6
KW  - chronic pain
KW  - nociceptor sensitization
KW  - hyperalgesia
KW  - allodynia
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140380
VL  - 7,73
ER  -