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  - Ben-Kraiem, Adel
A1  - Sauer, Reine-Solange
A1  - Norwig, Carla
A1  - Popp, Maria
A1  - Bettenhausen, Anna-Lena
A1  - Atalla, Mariam Sobhy
A1  - Brack, Alexander
A1  - Blum, Robert
A1  - Doppler, Kathrin
A1  - Rittner, Heike Lydia
T1  - Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy
JF  - Journal of Molecular Medicine
N2  - 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.
KW  - macrophages
KW  - neuropathy
KW  - barrier
KW  - pain
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265237
VL  - 99
IS  - 9
ER  -