TY  - JOUR
A1  - Oehler, Beatrice
A1  - Brack, Alexander
A1  - Blum, Robert
A1  - Rittner, Heike L.
T1  - Pain Control by Targeting Oxidized Phospholipids: Functions, Mechanisms, Perspectives
JF  - Frontiers in Endocrinology
N2  - Within the lipidome oxidized phospholipids (OxPL) form a class of chemically highly reactive metabolites. OxPL are acutely produced in inflamed tissue and act as endogenous, proalgesic (pain-inducing) metabolites. They excite sensory, nociceptive neurons by activating transient receptor potential ion channels, specifically TRPA1 and TRPV1. Under inflammatory conditions, OxPL-mediated receptor potentials even potentiate the action potential firing rate of nociceptors. Targeting OxPL with D-4F, an apolipoprotein A-I mimetic peptide or antibodies like E06, specifically binding oxidized headgroups of phospholipids, can be used to control acute, inflammatory pain syndromes, at least in rodents. With a focus on proalgesic specificities of OxPL, this article discusses, how targeting defined substances of the epilipidome can contribute to mechanism-based therapies against primary and secondary chronic inflammatory or possibly also neuropathic pain.
KW  - oxidized phospholipids
KW  - TRP channel
KW  - ion channel
KW  - analgesia
KW  - pain therapy
KW  - nociception
KW  - therapeutic antibody
KW  - mimetic peptide
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223432
SN  - 1664-2392
VL  - 11
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  -