15853
2017
eng
5447
7
article
1
2018-03-06
--
--
Inflammatory pain control by blocking oxidized phospholipid-mediated TRP channel activation
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.
Scientific Reports
10.1038/s41598-017-05348-3
urn:nbn:de:bvb:20-opus-158536
Scientific Reports 7:5447 (2017). DOI: : 10.1038/s41598-017-05348-3
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Beatrice Oehler
Katrin Kistner
Corinna Martin
Jürgen Schiller
Rafaela Mayer
Milad Mohammadi
Reine-Solange Sauer
Milos R. Filipovic
Francisco R. Nieto
Jan Kloka
Diana Pflücke
Kerstin Hill
Michael Schaefer
Marzia Malcangio
Peter W. Reeh
Alexander Brack
Robert Blum
Heike L. Rittner
eng
uncontrolled
chronic pain
eng
uncontrolled
ion channels in the nervous system
eng
uncontrolled
molecular medicine
eng
uncontrolled
pain
Medizin und Gesundheit
open_access
Institut für Klinische Neurobiologie
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Förderzeitraum 2017
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/15853/Oehler_Scientific_Reports.pdf
26523
2021
eng
1237–1250
9
99
article
1
--
--
--
Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy
Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN. In this study, we analyzed the spatiotemporal tight junction protein profile, barrier permeability, and vessel-associated macrophages in Wistar rats with streptozotocin-induced DPN. In these rats, mechanical hypersensitivity developed after 2 weeks and loss of motor function after 8 weeks, while the BNB and the blood-DRG barrier were leakier for small, but not for large molecules after 8 weeks only. The blood-spinal cord barrier remained sealed throughout the observation period. No gross changes in tight junction protein or cytokine expression were observed in all barriers to blood. However, expression of Cldn1 mRNA in perineurium was specifically downregulated in conjunction with weaker vessel-associated macrophage shielding of the BNB. Our results underline the role of specific tight junction proteins and BNB breakdown in DPN maintenance and differentiate DPN from traumatic nerve injury. Targeting claudins and sealing the BNB could stabilize pain and prevent further nerve damage.
Journal of Molecular Medicine
10.1007/s00109-021-02091-1
urn:nbn:de:bvb:20-opus-265237
publish
Journal of Molecular Medicine 2021, 99(9):1237–1250. DOI: 10.1007/s00109-021-02091-1
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Adel Ben-Kraiem
Reine-Solange Sauer
Carla Norwig
Maria Popp
Anna-Lena Bettenhausen
Mariam Sobhy Atalla
Alexander Brack
Robert Blum
Kathrin Doppler
Heike Lydia Rittner
eng
uncontrolled
macrophages
eng
uncontrolled
neuropathy
eng
uncontrolled
barrier
eng
uncontrolled
pain
Medizin und Gesundheit
open_access
Institut für Klinische Neurobiologie
Neurologische Klinik und Poliklinik
Klinik und Poliklinik für Anästhesiologie (ab 2004)
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/26523/Ben-Kraiem_Molecular.pdf