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  1. Article ; Online: Ex vivo Release of Calcitonin Gene-Related Peptide from the Trigeminovascular System in Rodents.

    Rasmussen, Rikke H / Jansen-Olesen, Inger / Kristensen, David M / Christensen, Sarah L

    Journal of visualized experiments : JoVE

    2022  , Issue 183

    Abstract: Calcitonin gene-related peptide (CGRP) was first discovered in the 1980s as a splice variant from the calcitonin gene. Since its discovery, its role in migraine pathophysiology has been well established, first by its potent vasodilator properties and ... ...

    Abstract Calcitonin gene-related peptide (CGRP) was first discovered in the 1980s as a splice variant from the calcitonin gene. Since its discovery, its role in migraine pathophysiology has been well established, first by its potent vasodilator properties and subsequently by its presence and function as a neurotransmitter in the sensory trigeminovascular system. The migraine-provoking ability of CGRP gave support to the pharma industry to develop monoclonal antibodies and antagonists inhibiting the effect of CGRP. A new treatment paradigm has proven effective in the prophylactic treatment of migraine. One of the useful tools to further understand migraine mechanisms is the ex vivo model of CGRP release from the trigeminovascular system. It is a relatively simple method that can be used with various pharmacological tools to achieve know-how to further develop new effective migraine treatments. The present protocol describes a CGRP release model and the technique to quantify the effect of pharmacological agents on the amount of CGRP released from the trigeminovascular system in rodents. A procedure describing the experimental approach from euthanasia to the measurement of protein levels is provided. The essential isolation of the trigeminal ganglion and the trigeminal nucleus caudalis from both mice and rats and the preparation of rat dura mater are described in detail. Furthermore, representative results from both species (rats and mice) are presented. The technique is a key tool to investigate the molecular mechanisms involved in migraine pathophysiology by using various pharmacological compounds and genetically modified animals.
    MeSH term(s) Animals ; Calcitonin/metabolism ; Calcitonin Gene-Related Peptide/metabolism ; Mice ; Migraine Disorders/drug therapy ; Rats ; Rodentia/metabolism ; Trigeminal Ganglion/metabolism
    Chemical Substances Calcitonin (9007-12-9) ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
    Language English
    Publishing date 2022-05-16
    Publishing country United States
    Document type Journal Article ; Video-Audio Media ; Research Support, Non-U.S. Gov't
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/63723
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The PACAP pathway is independent of CGRP in mouse models of migraine: possible new drug target?

    Ernstsen, Charlotte / Christensen, Sarah L / Rasmussen, Rikke H / Nielsen, Brian S / Jansen-Olesen, Inger / Olesen, Jes / Kristensen, David M

    Brain : a journal of neurology

    2022  Volume 145, Issue 7, Page(s) 2450–2460

    Abstract: Calcitonin gene-related peptide (CGRP)-antagonizing drugs represent a major advance in migraine treatment. However, up to 50% of patients do not benefit from monoclonal antibodies against CGRP or its receptor. Here, we test the hypothesis that a closely ... ...

    Abstract Calcitonin gene-related peptide (CGRP)-antagonizing drugs represent a major advance in migraine treatment. However, up to 50% of patients do not benefit from monoclonal antibodies against CGRP or its receptor. Here, we test the hypothesis that a closely related peptide, pituitary adenylate cyclase-activating peptide (PACAP-38), works independently of CGRP and thus might represent a new, alternative drug target. To understand differences in CGRP- and PACAP-mediated migraine pain, we used mouse models of provoked migraine-like pain based on multiple stimulations and subsequent measurement of tactile sensitivity response with von Frey filaments. Genetically modified mice lacking either functional CGRP receptors (Ramp1 knockout) or TRPA1 channels (Trpa1 knockout) were used together with CGRP-targeting antibodies and chemical inhibitors in wild-type mice (ntotal = 299). Ex vivo myograph studies were used to measure dilatory responses to CGRP and PACAP-38 in mouse carotid arteries. PACAP-38 provoked significant hypersensitivity and dilated the carotid arteries independently of CGRP. In contrast, glyceryl trinitrate-induced hypersensitivity is dependent on CGRP. Contrary to previous results with the migraine-inducing substances glyceryl trinitrate, cilostazol and levcromakalim, PACAP-38-induced hypersensitivity worked only partially through inhibition of ATP-sensitive potassium channels. Using multiple migraine-relevant models, these findings establish the PACAP-38 pathway as distinct from other migraine provoking pathways such as CGRP and glyceryl trinitrate. PACAP antagonism may therefore be a novel therapeutic target of particular interest in patients unresponsive to CGRP-antagonizing drugs.
    MeSH term(s) Animals ; Calcitonin Gene-Related Peptide/metabolism ; Disease Models, Animal ; Mice ; Migraine Disorders/chemically induced ; Nitroglycerin/adverse effects ; Pain/metabolism ; Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism
    Chemical Substances Pituitary Adenylate Cyclase-Activating Polypeptide ; Nitroglycerin (G59M7S0WS3) ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
    Language English
    Publishing date 2022-02-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80072-7
    ISSN 1460-2156 ; 0006-8950
    ISSN (online) 1460-2156
    ISSN 0006-8950
    DOI 10.1093/brain/awac040
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ui II Zs.26: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Xenobiotic Exposure and Migraine-Associated Signaling: A Multimethod Experimental Study Exploring Cellular Assays in Combination with

    Rasmussen, Rikke H / Christensen, Sarah L / Calloe, Kirstine / Nielsen, Brian Skriver / Rehfeld, Anders / Taylor-Clark, Thomas E / Haanes, Kristian A / Taboureau, Olivier / Audouze, Karine / Klaerke, Dan A / Olesen, Jes / Kristensen, David M

    Environmental health perspectives

    2023  Volume 131, Issue 11, Page(s) 117003

    Abstract: Background: Mechanisms for how environmental chemicals might influence pain has received little attention. Epidemiological studies suggest that environmental factors such as pollutants might play a role in migraine prevalence. Potential targets for ... ...

    Abstract Background: Mechanisms for how environmental chemicals might influence pain has received little attention. Epidemiological studies suggest that environmental factors such as pollutants might play a role in migraine prevalence. Potential targets for pollutants are the transient receptor potential (TRP) channels ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), which on activation release pain-inducing neuropeptide calcitonin gene-related peptide (CGRP).
    Objective: In this study, we aimed to examine the hypothesis that environmental pollutants via TRP channel signaling and subsequent CGRP release trigger migraine signaling and pain.
    Methods: A calcium imaging-based screen of environmental chemicals was used to investigate activation of migraine pain-associated TRP channels TRPA1 and TRPV1. Based on this screen, whole-cell patch clamp and
    Results: A total of 16 out of the 52 screened environmental chemicals activated TRPA1 at 10 or
    Discussion: Here we show that multiple environmental pollutants interact with the TRPA1-CGRP migraine pain pathway. The data provide valuable insights into how environmental chemicals can interact with neurobiology and provide a potential mechanism for putative increases in migraine prevalence over the last decades. https://doi.org/10.1289/EHP12413.
    MeSH term(s) Mice ; Animals ; TRPA1 Cation Channel/physiology ; Calcitonin Gene-Related Peptide/metabolism ; Calcium/metabolism ; Xenobiotics ; Transient Receptor Potential Channels/metabolism ; Migraine Disorders/metabolism ; Pain ; Environmental Pollutants/toxicity
    Chemical Substances TRPA1 Cation Channel ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z) ; Calcium (SY7Q814VUP) ; Xenobiotics ; Transient Receptor Potential Channels ; Environmental Pollutants
    Language English
    Publishing date 2023-11-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 195189-0
    ISSN 1552-9924 ; 0091-6765 ; 1078-0475
    ISSN (online) 1552-9924
    ISSN 0091-6765 ; 1078-0475
    DOI 10.1289/EHP12413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 1360: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 379: Show issues

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  4. Article ; Online: CGRP-dependent signalling pathways involved in mouse models of GTN- cilostazol- and levcromakalim-induced migraine.

    Christensen, Sarah L / Rasmussen, Rikke H / Ernstsen, Charlotte / La Cour, Sanne / David, Arthur / Chaker, Jade / Haanes, Kristian A / Christensen, Søren T / Olesen, Jes / Kristensen, David M

    Cephalalgia : an international journal of headache

    2021  Volume 41, Issue 14, Page(s) 1413–1426

    Abstract: Background: Knowledge of exact signalling events during migraine attacks is lacking. Various substances are known to trigger migraine attacks in patients and calcitonin gene-related peptide antagonising drugs are effective against migraine pain. Here, ... ...

    Abstract Background: Knowledge of exact signalling events during migraine attacks is lacking. Various substances are known to trigger migraine attacks in patients and calcitonin gene-related peptide antagonising drugs are effective against migraine pain. Here, we investigated the signalling pathways involved in three different mouse models of provoked migraine and relate them to calcitonin gene-related peptide and other migraine-relevant targets.
    Methods: In vivo
    Results: Glyceryl trinitrate-induced hypersensitivity was dependent on both prostaglandins and transient receptor potential cation channel, subfamily A, member 1, whereas cilostazol- and levcromakalim-induced hypersensitivity were independent of both. All three migraine triggers activated calcitonin gene-related peptide signalling, as both receptor antagonism and antibody neutralisation of calcitonin gene-related peptide were effective inhibitors of hypersensitivity in all three models. Stimulation of trigeminal ganglia and brain stem tissue samples with cilostazol and levcromakalim did not result in release of calcitonin gene-related peptide, and vasodilation following levcromakalim stimulation was independent of CGRP receptor antagonism.
    Conclusion: The mouse models of glyceryl trinitrate-, cilostazol- and levcromakalim- induced migraine all involve calcitonin gene-related peptide signalling in a complex interplay between different cell/tissue types. These models are useful in the study of migraine mechanisms.
    MeSH term(s) Animals ; Calcitonin Gene-Related Peptide ; Cilostazol/toxicity ; Cromakalim ; Humans ; Mice ; Mice, Knockout ; Migraine Disorders ; Trigeminal Ganglion
    Chemical Substances Cromakalim (0G4X367WA3) ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z) ; Cilostazol (N7Z035406B)
    Language English
    Publishing date 2021-08-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604567-4
    ISSN 1468-2982 ; 0333-1024
    ISSN (online) 1468-2982
    ISSN 0333-1024
    DOI 10.1177/03331024211038884
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1645: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: Smooth muscle ATP-sensitive potassium channels mediate migraine-relevant hypersensitivity in mouse models.

    Christensen, Sarah L / Rasmussen, Rikke H / Cour, Sanne La / Ernstsen, Charlotte / Hansen, Thomas F / Kogelman, Lisette Ja / Lauritzen, Sabrina P / Guzaite, Gintare / Styrishave, Bjarne / Janfelt, Christian / Christensen, Søren T / Aziz, Qadeer / Tinker, Andrew / Jansen-Olesen, Inger / Olesen, Jes / Kristensen, David M

    Cephalalgia : an international journal of headache

    2021  Volume 42, Issue 2, Page(s) 93–107

    Abstract: Background: Opening of K: Methods: In mouse models, we administered levcromakalim intracerebroventricularly, intraperitoneally and intraplantarily and compared the nociceptive responses by von Frey and hotplate tests. Mice with a conditional loss-of- ... ...

    Abstract Background: Opening of K
    Methods: In mouse models, we administered levcromakalim intracerebroventricularly, intraperitoneally and intraplantarily and compared the nociceptive responses by von Frey and hotplate tests. Mice with a conditional loss-of-function mutation in the smooth muscle K
    Results: Systemic administration of levcromakalim induced hypersensitivity but central and local administration provided antinociception respectively no effect. The Kir6.1 smooth muscle knockout mouse was protected from both GTN and levcromakalim induced hypersensitivity, and their arteries had impaired dilatory response to the latter. mRNA and protein expression studies showed that trigeminal ganglia did not have significant K
    Conclusion: Hypersensitivity provoked by GTN and levcromakalim in mice is dependent on functional smooth muscle K
    MeSH term(s) Adenosine Triphosphate ; Animals ; Cromakalim/adverse effects ; Disease Models, Animal ; Humans ; KATP Channels/genetics ; KATP Channels/metabolism ; Mice ; Mice, Knockout ; Migraine Disorders ; Muscle, Smooth/metabolism ; RNA, Messenger
    Chemical Substances KATP Channels ; RNA, Messenger ; Cromakalim (0G4X367WA3) ; Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2021-11-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604567-4
    ISSN 1468-2982 ; 0333-1024
    ISSN (online) 1468-2982
    ISSN 0333-1024
    DOI 10.1177/03331024211053570
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1645: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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