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  - 
TY  - JOUR
A1  - Oehler, Beatrice
A1  - Kistner, Katrin
A1  - Martin, Corinna
A1  - Schiller, Jürgen
A1  - Mayer, Rafaela
A1  - Mohammadi, Milad
A1  - Sauer, Reine-Solange
A1  - Filipovic, Milos R.
A1  - Nieto, Francisco R.
A1  - Kloka, Jan
A1  - Pflücke, Diana
A1  - Hill, Kerstin
A1  - Schaefer, Michael
A1  - Malcangio, Marzia
A1  - Reeh, Peter W.
A1  - Brack, Alexander
A1  - Blum, Robert
A1  - Rittner, Heike L.
T1  - Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
JF  - Scientific Reports
N2  - Phospholipids occurring in cell membranes and lipoproteins are converted into oxidized phospholipids (OxPL) by oxidative stress promoting atherosclerotic plaque formation. Here, OxPL were characterized as novel targets in acute and chronic inflammatory pain. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) and its derivatives were identified in inflamed tissue by mass spectrometry and binding assays. They elicited calcium influx, hyperalgesia and induced pro-nociceptive peptide release. Genetic, pharmacological and mass spectrometric evidence in vivo as well as in vitro confirmed the role of transient receptor potential channels (TRPA1 and TRPV1) as OxPAPC targets. Treatment with the monoclonal antibody E06 or with apolipoprotein A-I mimetic peptide D-4F, capturing OxPAPC in atherosclerosis, prevented inflammatory hyperalgesia, and in vitro TRPA1 activation. Administration of D-4F or E06 to rats profoundly ameliorated mechanical hyperalgesia and inflammation in collagen-induced arthritis. These data reveal a clinically relevant role for OxPAPC in inflammation offering therapy for acute and chronic inflammatory pain treatment by scavenging OxPAPC.
KW  - chronic pain
KW  - ion channels in the nervous system
KW  - molecular medicine
KW  - pain
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158536
VL  - 7
IS  - 5447
ER  - 
TY  - JOUR
A1  - Kress, Michaela
A1  - Hüttenhofer, Alexander
A1  - Landry, Marc
A1  - Kuner, Rohini
A1  - Favereaux, Alexandre
A1  - Greenberg, David
A1  - Bednarik, Josef
A1  - Heppenstall, Paul
A1  - Kronenberg, Florian
A1  - Malcangio, Marzia
A1  - Rittner, Heike
A1  - Üçeyler, Nurcan
A1  - Trajanoski, Zlatko
A1  - Mouritzen, Peter
A1  - Birklein, Frank
A1  - Sommer, Claudia
A1  - Soreq, Hermona
T1  - microRNAs in nociceptive circuits as predictors of future clinical applications
JF  - Frontiers in Molecular Neuroscience
N2  - Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs – and microRNAs (miRNAs) in particular – regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesized as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioral components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals.
KW  - chronic pain
KW  - biomarker
KW  - polymorphism
KW  - miRNA-based diagnostics
KW  - miRNA expression patterns
KW  - miRNA polymorphisms
KW  - antagomir
KW  - miRNA-based analgesic
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154597
VL  - 6
IS  - 33
ER  -