Review
Biochemistry & Molecular Biology
Linda Sangalli, Bradley Eli, Sachi Mehrotra, Suzan Sabagh, James Fricton
Summary: A bidirectional causal relationship has been found between temporomandibular disorders (TMDs) and chronic headaches, which might result from the shared biomolecular mechanisms of peripheral and central sensitization. The initiation of these processes involves inflammation and is likely mediated by key molecules, such as calcitonin gene-related peptide (CGRP). This scoping review suggests that CGRP-mediated neuroinflammation in the trigeminal ganglion may partially explain the bidirectional link between TMDs and chronic headaches. The clinical implications of this neuropathologic process are also briefly discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Xing Wang, Yuqi Chen, Jinlei Song, Chao You
Summary: The study compared the efficacy of different monoclonal antibodies against CGRP or its receptor for adult patients with migraine, showing that most drugs performed similarly and were superior to placebo in terms of efficacy, but galcanezumab had slightly different safety profile.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Clinical Neurology
Betel Tesfay, William Kristian Karlsson, Rogelio Dominguez Moreno, Debbie L. Hay, Anders Hougaard
Summary: The purpose of this study was to provide an overview of clinical studies on CGRP measurements in body fluids of migraine patients and to discuss the validity of CGRP measurement as a clinical biomarker of migraine. Several studies have reported increased CGRP levels in various body fluids of migraine patients, suggesting that CGRP may be a feasible biomarker. However, inconsistencies and methodological challenges in measuring CGRP levels exist. CGRP measurements may have potential as biomarkers for predicting response to migraine therapy.
CURRENT OPINION IN NEUROLOGY
(2022)
Article
Clinical Neurology
Alba Lopez-Bravo, Antonio Oliveros-Cid, Ane Minguez-Olaondo, Maria Luz Cuadrado
Summary: This article reports a case of high-frequency episodic migraine with symptoms of NH. After ineffective treatments, NH was remitted with the use of galcanezumab, a monoclonal antibody against CGRP. This suggests a potential role of CGRP in the pathogenesis of NH and calls for further investigation.
Article
Clinical Neurology
Abhijeet Jakate, Andrew M. Blumenfeld, Ramesh Boinpally, Matthew Butler, Lisa Borbridge, Janette Contreras-De Lama, Danielle McGeeney, Antonia Periclou, Richard B. Lipton
Summary: The study evaluated the impact of two CGRP-targeted mAbs, erenumab and galcanezumab, on the PK profile, safety, and tolerability of ubrogepant in adults with migraine. The results showed that coadministration of ubrogepant with erenumab or galcanezumab did not significantly alter the PK profile of ubrogepant and had no safety concerns.
Article
Clinical Neurology
Xing Wang, Qiang He, Dingke Wen, Lu Ma, Chao You
Summary: The study showed that both erenumab 70 mg and 140 mg reduced monthly migraine days in adult patients with migraine, with erenumab 140 mg demonstrating significantly better efficacy than 70 mg. Neither dosage was associated with increased risk of treatment-emergent adverse events. Future randomized controlled trials with larger sample sizes are needed to validate these findings.
NEUROLOGICAL SCIENCES
(2022)
Article
Anesthesiology
Diessica P. Dalenogare, Maria C. Theisen, Diulle S. Peres, Maria F. P. Fialho, Nathaly Andrighetto, Laura Barros, Lorenzo Landini, Mustafa Titiz, Francesco De Logu, Sara M. Oliveira, Pierangelo Geppetti, Romina Nassini, Gabriela Trevisan
Summary: This study investigated the mechanism of headaches in patients with multiple sclerosis (MS) using a mouse model, and found that TRPA1 plays a role in regulating periorbital mechanical allodynia (PMA). The study also suggested that oxidative stress may be a key factor in the development of headaches.
Article
Dentistry, Oral Surgery & Medicine
M. Takiguchi, I Sato, Z. L. Li, H. Miyaso, S. Kawata, M. Itoh
Summary: This study investigated the detailed morphological characteristics of mandibular canal branches (MCBs) using CBCT and observing the distribution of CGRP around the MCB. It found correlations between the structure of MCBs and CGRP distribution, with most MCBs following a clockwise distribution pattern and positive CGRP reactions observed in the no-canal branch group. These findings provide valuable insights for MCB dynamics and clinical dental treatment.
JOURNAL OF DENTAL RESEARCH
(2021)
Article
Anesthesiology
Casper E. Christensen, Samaira Younis, Ulrich Lindberg, Patrick de Koning, Daniel Tolnai, Olaf B. Paulson, Henrik B. W. Larsson, Faisal M. Amin, Messoud Ashina
Summary: The study found that during migraine attacks induced by calcitonin gene-related peptide and sildenafil, both the intradural middle meningeal artery and the middle cerebral artery dilated, indicating that intradural vasculature is affected by trigeminal nociceptor activation during migraine attacks.
Article
Clinical Neurology
Simon Akerman, Daniela Salvemini, Marcela Romero-Reyes
Summary: This study aimed to investigate the role of reactive nitroxidative species in the mechanisms of migraine and identified peroxynitrite as a potential effective target for migraine treatment. Targeting reactive nitroxidative species with drugs can alleviate migraine-related pain responses.
Review
Clinical Neurology
Katharina Kamm
Summary: CGRP plays a significant role in migraine pathophysiology, with detection of the peptide providing crucial insights into migraine research. Despite conflicting results in detecting CGRP in peripheral blood, alternative methods such as detecting CGRP in saliva and tear fluid have been proposed.
FRONTIERS IN NEUROLOGY
(2022)
Review
Biochemistry & Molecular Biology
Adriano Bonura, Nicoletta Brunelli, Marilena Marcosano, Gianmarco Iaccarino, Luisa Fofi, Fabrizio Vernieri, Claudia Altamura
Summary: The calcitonin gene-related peptide (CGRP) is a neuropeptide with complex systemic impact beyond nociception. It plays a crucial role in vasodilation, inflammation, intestinal motility, and apoptosis. CGRP has contradictory effects, acting as a potent vasodilator in the cardiovascular system but not inducing arterial hypertension. It also exhibits both anti-inflammatory and pro-inflammatory effects as an immunomodulator.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Luigi Francesco Iannone, Davide Fattori, Pierangelo Geppetti, Francesco De Cesaris
Summary: This study described 4 patients with both chronic migraine and cluster headache who received Galcanezumab treatment for at least 3 months, showing improvement in migraine days, CH attacks, Headache Impact Test -6 item score, and acute medication use. No adverse events were reported.
NEUROLOGICAL SCIENCES
(2022)
Article
Anesthesiology
Agustin Melo-Carrillo, Andrew M. Strassman, Aaron J. Schain, Ron S. Broide, Brian B. Cai, Catherine Rheaume, Amy D. Brideau-Andersen, Sait Ashina, Yadira Flores-Montanez, Mitchell F. Brin, Rami Burstein
Summary: The study found that peripherally applied BoNT-A can shorten the period of spontaneous cortical activity depression following CSD, but does not prevent induction or propagation of CSD. It also found that cleaved SNAP25, a tool for determining the anatomical targeting of BoNT-A treatment, can be readily detected at injection sites and intracranial nerve fibers, but not within cortical areas affected by CSD.
Review
Biochemistry & Molecular Biology
Qichang Wang, Haotian Qin, Jiapeng Deng, Huihui Xu, Su Liu, Jian Weng, Hui Zeng
Summary: Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide initially known for its vasodilatory and nociceptive effects. Recent research has revealed its close association with bone metabolism and shown CGRP to be a bridge between the nervous system and the skeletal muscle system. CGRP can promote osteogenesis, inhibit bone resorption, stimulate vascular growth, and regulate the immune microenvironment. Various signaling pathways, including the G protein-coupled pathway, MAPK, Hippo, and NF-κB, play a role in CGRP's effects on cell proliferation and differentiation. This review provides a comprehensive overview of the bone repair effects of CGRP and discusses therapeutic approaches such as drug injection, gene editing, and novel bone repair materials.
Article
Clinical Neurology
Franziska Guenther, Ferdinand Swozil, Stefan Heber, Michael Buchfelder, Karl Messlinger, Michael J. M. Fischer
Article
Cardiac & Cardiovascular Systems
Stefan Heber, Beatrix Fischer, Marina Sallaberger-Lehner, Maria Hausharter, Helmuth Ocenasek, Andreas Gleiss, Michael J. M. Fischer, Rochus Pokan, Alice Assinger, Ivo Volf
Article
Engineering, Biomedical
A. Mazare, J. Park, S. Simons, S. Mohajernia, I. Hwang, J. E. Yoo, H. Schneider, M. J. Fischer, P. Schmuki
ACTA BIOMATERIALIA
(2019)
Letter
Cell Biology
Lisa A. Gebhardt, Tetyana I. Kichko, Michael J. M. Fischer, Peter W. Reeh
JOURNAL OF CELL BIOLOGY
(2020)
Review
Clinical Neurology
Cosmin I. Ciotu, Michael J. M. Fischer
Article
Physiology
Clara Hoebart, Natalia S. Rojas-Galvan, Cosmin I. Ciotu, Ibrahim Aykac, Lukas F. Reissig, Wolfgang J. Weninger, Attila Kiss, Bruno K. Podesser, Michael J. M. Fischer, Stefan Heber
Summary: The study aims to determine the expression site of TRPA1 in the heart, specifically focusing on cardiomyocytes. However, the findings indicate that TRPA1 does not have a direct effect on cardiomyocytes, despite its important role in cardiac physiology and pathophysiology.
Article
Biochemistry & Molecular Biology
Tom Zimmermann, Lisa A. Gebhardt, Lucas Kreiss, Christin Schneider, Stephanie Arndt, Sigrid Karrer, Oliver Friedrich, Michael J. M. Fischer, Anja-Katrin Bosserhoff
Summary: CAP is a partially ionized gas with reported antitumor effects, but its active components and molecular mechanisms are not fully understood. This study characterized the impact of acidified nitrite on melanoma cells, demonstrating a synergistic effect with acidification leading to strong cytotoxicity. It also highlighted the importance of RNS during CAP treatment and evaluated important molecular mechanisms involved in the cancer cell response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Dragos Paul Mihai, Anca Ungurianu, Cosmin I. Ciotu, Michael J. M. Fischer, Octavian Tudorel Olaru, George Mihai Nitulescu, Corina Andrei, Cristina Elena Zbarcea, Anca Zanfirescu, Oana Cristina Seremet, Cornel Chirita, Simona Negres
Summary: MS is a demyelinating, autoimmune disease affecting a large number of young adults, in need of novel therapies. Venlafaxine and risperidone were found to improve motor performance and sensitivity to a cold stimulus, while all drugs alleviated cuprizone-induced deficits in superoxide dismutase activity. Agonistic activity of febuxostat may be useful for discovering novel TRPA1 ligands.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Marco Sisignano, Michael J. M. Fischer, Gerd Geisslinger
Summary: The proton-sensing G-protein coupled receptors, including GPR4, TDAG8, OGR1, and G2A, act as cellular sensors of acidification with varying pH detection capabilities. While initially thought to detect acidic cellular environments in inflammation, recent studies reveal their diverse roles in tumor biology, cardiovascular physiology, asthma, mechanosensation, and other processes. Each receptor has unique properties and potential roles in various physiological and pathophysiological conditions, highlighting the need for further research on their biological and pharmacological contexts.
Article
Biochemistry & Molecular Biology
Stefan Heber, Paul M. Haller, Attila Kiss, Bernhard Jaeger, Kurt Huber, Michael J. M. Fischer
Summary: This study found that methylglyoxal (MG) levels increase in the plasma of humans following acute myocardial infarction (AMI), and this increase is associated with a decrease in left ventricular ejection fraction (LVEF). MG levels increase after reperfusion and gradually decrease after 24 hours. The increase in MG is largely independent of cardiac necrosis markers, suggesting the presence of mechanisms independent of myocardial necrosis. The study also found that the increase in MG explains 23% of the variation in LVEF. Therefore, inhibiting MG generation or scavenging MG may be a novel therapeutic strategy to target post-AMI myocardial remodeling and dysfunction.
Article
Neurosciences
Cosmin I. Ciotu, Katrin Kistner, Ulrich Kaindl, Flavia Millesi, Tamara Weiss, Christine Radtke, Andreas Kremer, Katy Schmidt, Michael J. M. Fischer
Summary: Signal propagation is the key function of nerves. Lysophosphatidic acid 18:1 (LPA) selectively stimulates calcium signaling in Schwann cells but not neurons. Experimental observations in mice show clear changes in axonal function, with slowing and amplitude reduction in compound action potentials due to LPA exposure. Structural investigations reveal that LPA leads to evagination of axons in rat nerves, affecting myelination and conduction velocity. These structural and functional changes might explain sensory sensations such as itch and pain.
Article
Biochemistry & Molecular Biology
Clara Hoebart, Attila Kiss, Patrick M. Pilz, Petra L. Szabo, Bruno K. Podesser, Michael J. M. Fischer, Stefan Heber
Summary: This study aims to investigate the effects of TRPA1 activation, inhibition, or absence on infarcts and explore the underlying mechanisms. In vivo experiments showed no significant differences in infarct size among different TRPA1 activation or inhibition groups compared to the control group. In vitro experiments demonstrated that the presence of sensory neurons, partly dependent on TRPA1, increased the survival probability of cardiomyocytes challenged by ischemia-reperfusion. These findings raise doubts about the potential of TRPA1 as a promising target for reducing myocardial damage within a 24-hour period.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jan-Luca Stampf, Cosmin I. Ciotu, Stefan Heber, Stefan Boehm, Michael J. M. Fischer, Isabella Salzer
Summary: The mechanism of acetaminophen (APAP) analgesia is not fully understood. In this study, it was found that the APAP metabolite N-acetyl-p-benzoquinone imine (NAPQI) activates Kv7 channels in neurons, leading to a decrease in neuronal firing. The Kv7 channel blocker XE991 was shown to reduce the analgesic effect of APAP on mechanical pain in vivo.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physiology
Kristina Rodionova, Roland Veelken, Karl F. Hilgers, Eva-Maria Paulus, Peter Linz, Michael J. M. Fischer, Martina Schenker, Peter Reeh, Gisa Tiegs, Christian Ott, Roland Schmieder, Mario Schiffer, Kerstin Amann, Tilmann Ditting
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2020)
Article
Hematology
Petra Aigner, Tatsuaki Mizutani, Jaqueline Horvath, Thomas Eder, Stefan Heber, Karin Lind, Valentin Just, Herwig P. Moll, Assa Yeroslaviz, Michael J. M. Fischer, Lukas Kenner, Balazs Gyorffy, Heinz Sill, Florian Grebient, Richard Moriggl, Emilio Casanova, Dagmar Stoiber