6231
2010
eng
article
1
2012-10-31
--
--
MDL-28170 Has No Analgesic Effect on CCI Induced Neuropathic Pain in Mice
The calpain inhibitor MDL-28710 blocks the early local pro-inflammatory cytokine gene expression in mice after chronic constriction nerve injury (CCI). Onehundred- thirteen wild type mice of C57Bl/6J background received CCI of the right sciatic nerve. Mechanical paw withdrawal thresholds and thermal withdrawal latencies were investigated at baseline and at 1, 3, and 7 days after CCI. Three application regimens were used for MDL-28170: a) single injection 40 min before CCI; b) serial injections of MDL- 28170 40 min before and up to day three after CCI; c) sustained application via intraperitoneal osmotic pumps. The control animals received the vehicle DMSO/PEG 400. The tolerable dose of MDL-28170 for mice was 30 mg/kg body weight, higher doses were lethal within the first hours after application. Mechanical withdrawal thresholds and thermal withdrawal latencies were reduced after CCI and did not normalize after single or serial injections, nor with application of MDL-28170 via osmotic pumps. Although the calpain inhibitor MDL-28170 inhibits the early local cytokine upregulation in the sciatic nerve after CCI, pain behavior is not altered. This finding implies that local cytokine upregulation after nerve injury alone is only one factor in the induction and maintenance of neuropathic pain.
urn:nbn:de:bvb:20-opus-68359
6835
In: Molecules (2010) 15, 5, 3038-3047, DOI: 10.3390/molecules15053038
Nurcan Ueceyler
Lydia Biko
Claudia Sommer
deu
swd
Medizin
eng
uncontrolled
calpain
eng
uncontrolled
neuropathic pain
eng
uncontrolled
MDL-28170
eng
uncontrolled
chronic constriction nerve injury (CCI)
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6231/Sommer060_molecules_15_03038.pdf
6230
2010
eng
article
1
2012-10-31
--
--
Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice
Background: Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results: Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund’s adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1b), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1b. The increase of the antiinflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1b, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion: These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.
urn:nbn:de:bvb:20-opus-68349
6834
In: Molecular Pain (2010) 6, DOI: 10.1186/1744-8069-6-13
Yong Chen
Michael K. Boettger
Andreas Reif
Angelika Schmitt
Nurcan Ueceyler
Claudia Sommer
deu
swd
Medizin
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6230/sommer059_1744_8069_6_13.pdf
14038
2011
eng
1-9
7,73
article
1
2016-11-15
--
--
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 \(in\) \(vitro\)
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.
Molecular Pain
10.1186/1744-8069-7-73
urn:nbn:de:bvb:20-opus-140380
Molecular Pain 2011, 7:73
Serena Quarta
Christian Vogl
Cristina E. Constantin
Nurcan Üçeyler
Claudia Sommer
Michaela Kress
eng
uncontrolled
Leukemia Inhibitory Factor
eng
uncontrolled
Mediated Inflammatory Hyperalgesia
eng
uncontrolled
Necrosis-factor-Alpha
eng
uncontrolled
Oncostatin-M-Receptor
eng
uncontrolled
Rat Sensory Neurons
eng
uncontrolled
Rheumatoid-Arthritis
eng
uncontrolled
Interleukin-6-Deficient mice
eng
uncontrolled
Peripheral Inflammation
eng
uncontrolled
Thermal Hyperalgesia
eng
uncontrolled
Heat Hyperalgesia
eng
uncontrolled
proinflammatory cytokine
eng
uncontrolled
Interleukin-6
eng
uncontrolled
chronic pain
eng
uncontrolled
nociceptor sensitization
eng
uncontrolled
hyperalgesia
eng
uncontrolled
allodynia
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14038/061_Quarta_MOLECULAR-PAIN.pdf
14120
2011
eng
1-8
134
11
article
1
2016-11-30
--
--
Novel SCARB2 mutation in Action Myoclonus-Renal Failure syndrome and evaluation of SCARB2 mutations in isolated AMRF features
Background:
Action myoclonus-renal failure syndrome is a hereditary form of progressive myoclonus epilepsy associated with renal failure. It is considered to be an autosomal-recessive disease related to loss-of-function mutations in SCARB2. We studied a German AMRF family, additionally showing signs of demyelinating polyneuropathy and dilated cardiomyopathy. To test the hypothesis whether isolated appearance of individual AMRF syndrome features could be related to heterozygote SCARB2 mutations, we screened for SCARB2 mutations in unrelated patients showing isolated AMRF features.
Methods:
In the AMRF family all exons of SCARB2 were analyzed by Sanger sequencing. The mutation screening of unrelated patients with isolated AMRF features affected by either epilepsy (n = 103, progressive myoclonus epilepsy or generalized epilepsy), demyelinating polyneuropathy (n = 103), renal failure (n = 192) or dilated cardiomyopathy (n = 85) was performed as high resolution melting curve analysis of the SCARB2 exons.
Results:
A novel homozygous 1 bp deletion (c.111delC) in SCARB2 was found by sequencing three affected homozygous siblings of the affected family. A heterozygous sister showed generalized seizures and reduction of nerve conduction velocity in her legs. No mutations were found in the epilepsy, renal failure or dilated cardiomyopathy samples. In the polyneuropathy sample two individuals with demyelinating disease were found to be carriers of a SCARB2 frameshift mutation (c.666delCCTTA).
Conclusions:
Our findings indicate that demyelinating polyneuropathy and dilated cardiomyopathy are part of the action myoclonus-renal failure syndrome. Moreover, they raise the possibility that in rare cases heterozygous SCARB2 mutations may be associated with PNP features.
BMC Neurology
10.1186/1471-2377-11-134
urn:nbn:de:bvb:20-opus-141209
BMC Neurology 2011 11:134.
Franziska Hopfner
Barbara Schormair
Franziska Knauf
Achim Berthele
Thomas R. Tölle
Ralf Baron
Christoph Maier
Rolf-Detlef Treede
Andreas Binder
Claudia Sommer
Christian Maihöfner
Wolfram Kunz
Friedrich Zimprich
Uwe Heemann
Arne Pfeufer
Michael Näbauer
Stefan Kääb
Barbara Nowak
Christian Gieger
Peter Lichtner
Claudia Trenkwalder
Konrad Oexle
Juliane Winkelmann
eng
uncontrolled
Demyelinating peripheral neuropathy
eng
uncontrolled
Beta-glucocerebrosidase
eng
uncontrolled
Epilepsy
eng
uncontrolled
LIMP-2
eng
uncontrolled
Mice
Krankheiten
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14120/101_Hopfner_BMC-NEUROLOGY.pdf
14050
2011
eng
e16775
2
6
article
1
2016-11-17
--
--
Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats
Background:
Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear.
Methodology/Principal Findings:
We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11) C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient's amygdala/hippocampus complex. No motor abnormalities were found in recipient rats.
Conclusion/Significance:
The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.
Plos One
10.1371/journal.pone.0016775
urn:nbn:de:bvb:20-opus-140506
PLoS ONE 6(2):e16775. doi:10.1371/journal.pone.0016775
Christian Geis
Andreas Weishaupt
Benedikt Grünewald
Thomas Wultsch
Andreas Reif
Manfred Gerlach
Ron Dirkx
Michele Solimena
Klaus V Toyka
Franco Folli
Daniela Perani
Manfred Heckmann
Claudia Sommer
eng
uncontrolled
Glutamic-acid decarboxylase anxiety
eng
uncontrolled
spinal-cord-injury
eng
uncontrolled
presynaptic inhibition
eng
uncontrolled
65-kda isoform
eng
uncontrolled
fear memory
eng
uncontrolled
antibodies
eng
uncontrolled
disorder
eng
uncontrolled
neurons
eng
uncontrolled
anxiety
eng
uncontrolled
autoantibodies
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14050/067_Geis_PLOS-ONE.PDF
6351
2011
eng
article
1
2013-01-11
--
--
Human Stiff-Person Syndrome IgG Induces Anxious Behavior in Rats
Background: Anxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear. Methodology/Principal Findings: We re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11)C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient’s amygdala/hippocampus complex. No motor abnormalities were found in recipient rats. Conclusion/Significance: The observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.
urn:nbn:de:bvb:20-opus-74757
7475
In: PLOS ONE (2011) 6:2, 10.1371/journal.pone.0016775
Christian Geis
Andreas Weishaupt
Benedikt Grünewald
Thomas Wultsch
Andreas Reif
Manfred Gerlach
Ron Dirkx
Michele Solimena
Daniela Perani
Manfred Heckmann
Klaus V. Toyka
Franco Folli
Claudia Sommer
deu
swd
Medizin
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/6351/Geis_journal.pone.0016775.pdf
5973
2011
eng
article
1
2012-06-30
--
--
Systematic review with meta-analysis: Cytokines in fibromyalgia syndrome
Background: To perform a systematic review and meta-analysis on cytokine levels in patients with fibromyalgia syndrome (FMS). Methods: Through December 2010 we systematically reviewed the databases PubMed, MEDLINE, and PsycINFO and screened the reference lists of 22 review articles for suitable original articles. Original articles investigating cytokines in patients with FMS were included. Data were extracted by two independent authors. Differences of the cytokine levels of FMS patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed applying methodological scores: modified Center of Evidence Based Medicine, Newcastle-Ottawa-Scale, and Würzburg Methodological Quality Score. Results: Twenty-five articles were included investigating 1255 FMS patients and 800 healthy controls. Data of 13/25 studies entered meta-analysis. The overall methodological quality of studies was low. The results of the majority of studies were not comparable because methods, investigated material, and investigated target cytokines differed. Systematic review of the selected 25 articles revealed that FMS patients had higher serum levels of interleukin (IL)-1 receptor antagonist, IL-6, and IL-8, and higher plasma levels of IL-8. Meta-analysis of eligible studies showed that FMS patients had higher plasma IL-6 levels compared to controls (SMD = -0.34 [-0.64, -0.03] 95% CI; p = 0.03). The majority of investigated cytokines were not different between patients and controls. Conclusions: The pathophysiological role of cytokines in FMS is still unclear. Studies of higher quality and with higher numbers of subjects are needed.
urn:nbn:de:bvb:20-opus-69189
6918
BMC Musculoskeletal Disorders (2011) 12:245, doi:10.1186/1471-2474-12-245
Nurcan Üceyler
Winfried Häuser
Claudia Sommer
deu
swd
Fibromyalgie
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Förderzeitraum 2011
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5973/ueceyler_1471_2474_12_245.pdf
5764
2011
eng
article
1
2012-04-13
--
--
A modified score to identify and discriminate neuropathic pain: a study on the German version of the neuropathic pain symptom inventory (NPSI)
Background: Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain. Methods: We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles. Results: Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91%) and acceptable specificity (70%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct. Conclusions: The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain.
urn:nbn:de:bvb:20-opus-68716
6871
BMC Neurology (2011) 11:104, doi:10.1186/1471-2377-11-104
Claudia Sommer
Helmut Richter
Jan P. Rogausch
Jule Frettloh
Margitta Lungenhausen
Christoph Maier
deu
swd
Neuralgie
eng
uncontrolled
NPSI
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Förderzeitraum 2011
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5764/Sommer_1471_2377_11_104.pdf
5969
2011
eng
article
1
2012-06-30
--
--
Hypervigilance or avoidance of trigger related cues in migraineurs? - A case-control study using the emotional stroop task
Background: “Negative affect” is one of the major migraine triggers. The aim of the study was to assess attentional biases for negative affective stimuli that might be related to migraine triggers in migraine patients with either few or frequent migraine and healthy controls. Methods: Thirty-three subjects with frequent migraine (FM) or with less frequent episodic migraine, and 20 healthy controls conducted two emotional Stroop tasks in the interictal period. In task 1, general affective words and in task 2, pictures of affective faces (angry, neutral, happy) were used. For each task we calculated two emotional Stroop indices. Groups were compared using one-way ANOVAs. Results: The expected attentional bias in migraine patients was not found. However, in task 2 the controls showed a significant attentional bias to negative faces, whereas the FM group showed indices near zero. Thus, the FM group responded faster to negative than to positive stimuli. The difference between the groups was statistically significant. Conclusions: The findings in the FM group may reflect a learned avoidance mechanism away from affective migraine triggers.
urn:nbn:de:bvb:20-opus-69103
6910
BMC Neurology (2011) 11:141, doi:10.1186/1471-2377-11-141
Anne-Katrin Puschmann
Claudia Sommer
deu
swd
Migräne
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Förderzeitraum 2011
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/5969/puschmann_1471_2377_11_141.pdf
13775
2011
eng
141
11
article
1
2016-08-26
--
--
Hypervigilance or avoidance of trigger related cues in migraineurs? - A case-control study using the emotional stroop task
Background
"Negative affect" is one of the major migraine triggers. The aim of the study was to assess attentional biases for negative affective stimuli that might be related to migraine triggers in migraine patients with either few or frequent migraine and healthy controls.
Methods
Thirty-three subjects with frequent migraine (FM) or with less frequent episodic migraine, and 20 healthy controls conducted two emotional Stroop tasks in the interictal period. In task 1, general affective words and in task 2, pictures of affective faces (angry, neutral, happy) were used. For each task we calculated two emotional Stroop indices. Groups were compared using one-way ANOVAs.
Results
The expected attentional bias in migraine patients was not found. However, in task 2 the controls showed a significant attentional bias to negative faces, whereas the FM group showed indices near zero. Thus, the FM group responded faster to negative than to positive stimuli. The difference between the groups was statistically significant.
Conclusions
The findings in the FM group may reflect a learned avoidance mechanism away from affective migraine triggers.
BMC Neurology
10.1186/1471-2377-11-141
urn:nbn:de:bvb:20-opus-137750
BMC Neurology 2011, 11:141. DOI 10.1186/1471-2377-11-141
Anne-Katrin Puschmann
Claudia Sommer
eng
uncontrolled
migraineur
eng
uncontrolled
cue
Krankheiten
open_access
Neurologische Klinik und Poliklinik
Förderzeitraum 2011
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13775/Puschmann_1471-2377-11-141.pdf