A5066815637- Pain Mechanisms and Treatments
- Ion Channels and Receptors
- Cancer Treatment and Pharmacology
- Sphingolipid Metabolism and Signaling
- Eicosanoids and Hypertension Pharmacology
- Pharmacological Effects of Natural Compounds
- Hormonal Regulation and Hypertension
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Peripheral Neuropathies and Disorders
- Ocular Surface and Contact Lens
- Pain Management and Placebo Effect
- Pharmacological Receptor Mechanisms and Effects
- Pharmacogenetics and Drug Metabolism
- Signaling Pathways in Disease
- Aldose Reductase and Taurine
- Ion channel regulation and function
- Free Radicals and Antioxidants
- Plant-based Medicinal Research
- Nerve injury and regeneration
- Olfactory and Sensory Function Studies
- Neurobiology and Insect Physiology Research
- Heat shock proteins research
- Herbal Medicine Research Studies
- Botulinum Toxin and Related Neurological Disorders
Goethe University Frankfurt
2016-2025
Fraunhofer Institute for Translational Medicine and Pharmacology
2020-2025
Merck (Germany)
2022-2024
University Hospital Frankfurt
2018-2023
Endokrinologikum
2023
Fraunhofer Institute for Molecular Biology and Applied Ecology
2020
Epoxyeicosatrienoic acids (EETs) are cytochrome P450-epoxygenase-derived metabolites of arachidonic acid that act as endogenous signaling molecules in multiple biological systems. Here we have investigated the specific contribution 5,6-EET to transient receptor potential (TRP) channel activation nociceptor neurons and its consequence for nociceptive processing. We found that, during capsaicin-induced nociception, levels increased dorsal root ganglia (DRGs) spinal cord, is released from...
Significance Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a severe side effect that affects up to 80% of patients during cancer treatment. Pharmacological treatment options are poor, as CIPNP differs mechanistically from other chronic states. Here, we describe mechanism by which pronociceptive oxidized lipid mediators generated the cytochrome P 450 -epoxygenase CYP2J2 in sensory neurons CIPNP. Blocking synthesis these lipids with telmisartan, identified potent inhibitor large...
Specific somatosensations may be processed by different subsets of primary afferents. C-fibers expressing heat-sensitive TRPV1 channels are proposed, for example, to heat but not mechanical pain detectors. To phenotype in rats the sensory function + afferents, we rapidly and selectively silenced only their activity, introducing membrane-impermeant sodium channel blocker QX-314 into these axons via pore. Using tandem mass spectrometry show that upon activation with capsaicin, accumulates...
Dry eye disease (DED) is often seen in patients with polyneuropathies (PNs), but the relationship between different forms of PNs and DED not known. In oxaliplatin (Ox-)-treated mice PNs, morphological changes sciatic nerve (SN), dorsal root ganglia (DRG), trigeminal (TG), ocular tissues involved tear formation were investigated. addition, proteomics gene expression related proteins surface as well inflammatory factors analyzed. There significant six compared to controls, respective tissues....
Emerging lines of evidence indicate that production reactive oxygen species (ROS) at distinct sites the nociceptive system contributes to processing neuropathic pain. However, mechanisms underlying ROS during pain are not fully understood. We here detected ROS-generating nicotinamide adenine dinucleotide phosphate oxidase isoform Nox2 in macrophages dorsal root ganglia (DRG) mice. In response peripheral nerve injury, Nox2-positive were recruited DRG, and was increased a Nox2-dependent...
Abstract Chemotherapy-induced peripheral neuropathic pain (CIPN) is a common and severe debilitating side effect of many widely used cytostatics. However, there no approved pharmacological treatment for CIPN available. Among other substances, oxaliplatin causes in up to 80% treated patients. Here, we report the involvement G-protein coupled receptor G2A (GPR132) oxaliplatin-induced mice. We found that mice deficient G2A-receptor show decreased mechanical hypersensitivity after treatment....
Background and Purpose Selective nociceptor fibre block is achieved by introducing the cell membrane impermeant sodium channel blocker lidocaine N‐ethyl bromide ( QX ‐314) through transient receptor potential V 1 TRPV1) channels into nociceptors. We screened local anaesthetics for their capacity to activate TRP channels, characterized nerve obtained combination with ‐314. Experimental Approach investigated activation in dorsal root ganglion DRG ) neurons calcium imaging patch‐clamp...
Ultraviolet-B (UVB)-induced inflammation produces a dose-dependent mechanical and thermal hyperalgesia in both humans rats, most likely via inflammatory mediators acting at the site of injury. Previous work has shown that gene expression cytokines chemokines is positively correlated between species these factors can contribute to UVB-induced pain. In order investigate other potential pain this model we used RNA-seq perform genome-wide transcriptional profiling human rat skin peak...
Platelets are well known for their role in hemostasis but also increasingly recognized supporting innate immune responses. Here, we studied the of platelets development peripheral inflammation and found that colocalize with macrophages inflamed tissue outside blood vessels different animal models cutaneous inflammation. Collagen-treatment isolated from paws during zymosan-induced induced thromboxane synthesis through platelet-expressed collagen receptor glycoprotein VI. Deletion VI or its...
Oxaliplatin, a platinum-based chemotherapeutic drug, which is used as first-line treatment for some types of colorectal carcinoma, causes peripheral neuropathic pain in patients. In addition, an acute syndrome develop almost 90% patients immediately after oxaliplatin treatment, poorly understood mechanistically but correlates with incidence and severity the later-occurring neuropathy. Here we investigated effects murine model, showing that male female mice mechanical hypersensitivity 24 h...
Neuropathic pain is experienced worldwide by patients suffering from nerve injuries, infectious or metabolic diseases chemotherapy. However, the treatment options are still limited because of low efficacy and sometimes severe side effects. Recently, deficiency FKBP51 was shown to relieve chronic pain, revealing as a potential therapeutic target. specific potent inhibitor not available until recently which hampered targeting FKBP51.In this study, we used well-established robust spared injury...
In recent years, the selective inhibition of FKBP51 has emerged as a possible treatment for chronic pain, obesity-induced diabetes, or depression. All currently known advanced FKBP51-selective inhibitors, including widely used SAFit2, contain cyclohexyl residue key motif enabling selectivity over closest homologue and anti-target FKBP52. During structure-based SAR exploration, we surprisingly discovered thiophenes highly efficient replacement moieties that retain strong SAFit-type inhibitors...
Large conductance calcium-activated potassium (BKCa) channels are important regulators of neuronal excitability. Although there is electrophysiological evidence for BKCa channel expression in sensory neurons, their vivo functions pain processing have not been fully defined. Using a specific antibody, we demonstrate here that expressed subpopulations peptidergic and nonpeptidergic nociceptors. To test functional association activity neurons with particular modalities, generated mice which...
Background: Cytochrome-P450 (CYP450) epoxygenases metabolise arachidonic acid (AA) into four different biologically active epoxyeicosatrienoic (EET) regioisomers. Three of the EETs (i.e., 8,9-, 11,12- and 14,15-EET) are rapidly hydrolysed by enzyme soluble epoxide hydrolase (sEH). Here, we investigated role sEH in nociceptive processing during peripheral inflammation. Results: In dorsal root ganglia (DRG), found that is expressed medium large diameter neurofilament 200-positive neurons....
Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including number oxidized lipids, some which serve modulators sensory TRP-channels. These lipids are eicosanoids the arachidonic acid and linoleic pathway, as well lysophophatidic acids (LPAs). However, their regulation pattern contribution to peripheral still unclear. Here, we used UVB-model for investigate alterations lipid concentrations at site inflammation, dorsal root ganglia...
Macrophages are highly versatile cells, which acquire, depending on their microenvironment, pro- (M1-like) or antiinflammatory (M2-like) phenotypes. Here, we studied the role of G-protein coupled receptor G2A (GPR132), in chemotactic migration and polarization macrophages, using zymosan-model acute inflammation. G2A-deficient mice showed a reduced zymosan-induced thermal hyperalgesia, was reversed after macrophage depletion. Fittingly, number M1-like macrophages inflamed tissue mice....