14278
2011
eng
e17387
3
6
article
1
2017-01-11
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Transient Receptor Potential Channel Polymorphisms Are Associated with the Somatosensory Function in Neuropathic Pain Patients
Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p=0.03), and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V) with cold hypoalgesia (p=0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p=0.006, p=0.005 and p<0.001) and transient receptor potential vanilloid 1 1103C>G (rs222747, M315I) to cold hypaesthesia (p=0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients.
PLoS ONE
10.1371/journal.pone.0017387
urn:nbn:de:bvb:20-opus-142782
PLoS ONE 6(3): e17387. doi:10.1371/journal.pone.0017387
true
true
Andreas Binder
Denisa May
Ralf Baron
Christoph Maier
Thomas R. Tölle
Rolf-Detlef Treede
Achim Berthele
Frank Faltraco
Herta Flor
Janne Gierthmühlen
Sierk Haenisch
Volker Huge
Walter Magerl
Christian Maihöfner
Helmut Richter
Roman Rolke
Andrea Scherens
Nurcan Üçeyler
Mike Ufer
Gunnar Wasner
Jihong Zhu
Ingolf Cascorbi
eng
uncontrolled
Paradoxical heat sensation
eng
uncontrolled
Neurogenic inflammation
eng
uncontrolled
Capsaicin receptor
eng
uncontrolled
TRP Channels
eng
uncontrolled
Cold
eng
uncontrolled
Mechanisms
eng
uncontrolled
Hyperalgesia
eng
uncontrolled
Sensitivity
eng
uncontrolled
Expression
eng
uncontrolled
Stimuli
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/14278/149_Binder_PLOS-ONE.PDF
14120
2011
eng
1-8
134
11
article
1
2016-11-30
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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
11304
2014
eng
article
1
2015-05-11
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Local and Systemic Cytokine Expression in Patients with Postherpetic Neuralgia
Background
Postherpetic neuralgia (PHN) is the painful complication of a varicella zoster virus reactivation. We investigated the systemic and local gene expression of pro- and anti-inflammatory cytokine expression in patients with PHN.
Methods
Thirteen patients with PHN at the torso (Th4-S1) were recruited. Skin punch biopsies were obtained from the painful and the contralateral painless body area for intraepidermal nerve fiber density (IENFD) and cytokine profiling. Additionally, blood was withdrawn for systemic cytokine expression and compared to blood values of healthy controls. We analyzed the gene expression of selected pro- and anti-inflammatory cytokines (tumor necrosis factor-alpha [TNF] and interleukins [IL]-1β, IL-2, and IL-8).
Results
IENFD was lower in affected skin compared to unaffected skin (p<0.05), while local gene expression of pro- and anti-inflammatory cytokines did not differ except for two patients who had 7fold higher IL-6 and 10fold higher IL-10 gene expression in the affected skin compared to the contralateral unaffected skin sample. Also, the systemic expression of cytokines in patients with PHN and in healthy controls was similar.
Conclusion
While the systemic and local expression of the investigated pro- and anti-inflammatory cytokines was not different from controls, this may have been influenced by study limitations like the low number of patients and different disease durations. Furthermore, other cytokines or pain mediators need to be considered.
10.1371/journal.pone.0105269
urn:nbn:de:bvb:20-opus-113041
PLoS ONE 9(8): e105269. doi:10.1371/journal.pone.0105269
Nurcan Üçeyler
Michael Valet
Waldemar Kafke
Thomas R. Tölle
Claudia Sommer
eng
uncontrolled
neuropathic pain
eng
uncontrolled
cytokines
eng
uncontrolled
pain sensation
eng
uncontrolled
gene expression
eng
uncontrolled
nerve fibres
eng
uncontrolled
RNA extraction
eng
uncontrolled
shingles
eng
uncontrolled
skin tumors
Medizin und Gesundheit
open_access
Neurologische Klinik und Poliklinik
Förderzeitraum 2014
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11304/111_Ueceyler_PLoS.pdf