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  1. Article: Vascular Contributions to Migraine: Time to Revisit?

    Mason, Bianca N / Russo, Andrew F

    Frontiers in cellular neuroscience

    2018  Volume 12, Page(s) 233

    Abstract: Migraine is one of the most prevalent and disabling neurovascular disorders worldwide. However, despite the increase in awareness and research, the understanding of migraine pathophysiology and treatment options remain limited. For centuries, migraine ... ...

    Abstract Migraine is one of the most prevalent and disabling neurovascular disorders worldwide. However, despite the increase in awareness and research, the understanding of migraine pathophysiology and treatment options remain limited. For centuries, migraine was considered to be a vascular disorder. In fact, the throbbing, pulsating quality of the headache is thought to be caused by mechanical changes in vessels. Moreover, the most successful migraine treatments act on the vasculature and induction of migraine can be accomplished with vasoactive agents. However, over the past 20 years, the emphasis has shifted to the neural imbalances associated with migraine, and vascular changes have generally been viewed as an epiphenomenon that is neither sufficient nor necessary to induce migraine. With the clinical success of peripherally-acting antibodies that target calcitonin gene-related peptide (CGRP) and its receptor for preventing migraine, this neurocentric view warrants a critical re-evaluation. This review will highlight the likely importance of the vasculature in migraine.
    Language English
    Publishing date 2018-08-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2018.00233
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Dural Stimulation and Periorbital von Frey Testing in Mice As a Preclinical Model of Headache.

    Mason, Bianca N / Avona, Amanda / Lackovic, Jacob / Dussor, Gregory

    Journal of visualized experiments : JoVE

    2021  , Issue 173

    Abstract: The cranial meninges, comprised of the dura mater, arachnoid, and pia mater, are thought to primarily serve structural functions for the nervous system. For example, they protect the brain from the skull and anchor/organize the vascular and neuronal ... ...

    Abstract The cranial meninges, comprised of the dura mater, arachnoid, and pia mater, are thought to primarily serve structural functions for the nervous system. For example, they protect the brain from the skull and anchor/organize the vascular and neuronal supply of the cortex. However, the meninges are also implicated in nervous system disorders such as migraine, where the pain experienced during a migraine is attributed to local sterile inflammation and subsequent activation of local nociceptive afferents. Of the layers in the meninges, the dura mater is of particular interest in the pathophysiology of migraines. It is highly vascularized, harbors local nociceptive neurons, and is home to a diverse array of resident cells such as immune cells. Subtle changes in the local meningeal microenvironment may lead to activation and sensitization of dural perivascular nociceptors, thus leading to migraine pain. Studies have sought to address how dural afferents become activated/sensitized by using either in vivo electrophysiology, imaging techniques, or behavioral models, but these commonly require very invasive surgeries. This protocol presents a method for comparatively non-invasive application of compounds on the dura mater in mice and a suitable method for measuring headache-like tactile sensitivity using periorbital von Frey testing following dural stimulation. This method maintains the integrity of the dura and skull and reduces confounding effects from invasive techniques by injecting substances through a 0.65 mm modified cannula at the junction of unfused sagittal and lambdoid sutures. This preclinical model will allow researchers to investigate a wide range of dural stimuli and their role in the pathological progression of migraine, such as nociceptor activation, immune cell activation, vascular changes, and pain behaviors, all while maintaining injury-free conditions to the skull and meninges.
    MeSH term(s) Animals ; Dura Mater ; Headache ; Meninges ; Mice ; Migraine Disorders ; Rats ; Rats, Sprague-Dawley
    Language English
    Publishing date 2021-07-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/62867
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: PAR2 activation in the dura causes acute behavioral responses and priming to glyceryl trinitrate in a mouse migraine model.

    Mason, Bianca N / Hassler, Shayne N / DeFea, Kathryn / Boitano, Scott / Vagner, Josef / Price, Theodore J / Dussor, Greg

    The journal of headache and pain

    2023  Volume 24, Issue 1, Page(s) 42

    Abstract: Background: Migraine is a severely debilitating disorder that affects millions of people worldwide. Studies have indicated that activation of protease-activated receptor-2 (PAR2) in the dura mater causes headache responses in preclinical models. It is ... ...

    Abstract Background: Migraine is a severely debilitating disorder that affects millions of people worldwide. Studies have indicated that activation of protease-activated receptor-2 (PAR2) in the dura mater causes headache responses in preclinical models. It is also well known that vasodilators such as nitric oxide (NO) donors can trigger migraine attacks in migraine patients but not controls. In the current study we examined whether activation of PAR2 in the dura causes priming to the NO donor glyceryl trinitrate (GTN).
    Methods: A preclinical behavioral model of migraine was used where stimuli (PAR2 agonists: 2at-LIGRL-NH
    Results: We found that application of the selective PAR2 agonist 2at-LIGRL-NH
    Conclusions: These results indicate that PAR2 activation in the meninges can cause acute headache behavioral responses and priming to an NO donor, and support further exploration of PAR2 as a novel therapeutic target for migraine.
    MeSH term(s) Mice ; Animals ; Nitroglycerin/pharmacology ; Leukocyte Elastase ; Receptor, PAR-2 ; Interleukin-6 ; Migraine Disorders/chemically induced ; Dura Mater ; Headache ; Disease Models, Animal
    Chemical Substances Nitroglycerin (G59M7S0WS3) ; Leukocyte Elastase (EC 3.4.21.37) ; Receptor, PAR-2 ; Interleukin-6
    Language English
    Publishing date 2023-04-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2036768-5
    ISSN 1129-2377 ; 1129-2369
    ISSN (online) 1129-2377
    ISSN 1129-2369
    DOI 10.1186/s10194-023-01574-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Dural stimulation and periorbital von frey testing in mice as a preclinical model of headache

    Mason, Bianca N. / Avona, Amanda / Lackovic, Jacob / Dussor, Gregory

    Journal of visualized experiments. 2021 July 29, , no. 173

    2021  

    Abstract: The cranial meninges, comprised of the dura mater, arachnoid, and pia mater, are thought to primarily serve structural functions for the nervous system. For example, they protect the brain from the skull and anchor/organize the vascular and neuronal ... ...

    Abstract The cranial meninges, comprised of the dura mater, arachnoid, and pia mater, are thought to primarily serve structural functions for the nervous system. For example, they protect the brain from the skull and anchor/organize the vascular and neuronal supply of the cortex. However, the meninges are also implicated in nervous system disorders such as migraine, where the pain experienced during a migraine is attributed to local sterile inflammation and subsequent activation of local nociceptive afferents. Of the layers in the meninges, the dura mater is of particular interest in the pathophysiology of migraines. It is highly vascularized, harbors local nociceptive neurons, and is home to a diverse array of resident cells such as immune cells. Subtle changes in the local meningeal microenvironment may lead to activation and sensitization of dural perivascular nociceptors, thus leading to migraine pain. Studies have sought to address how dural afferents become activated/sensitized by using either in vivo electrophysiology, imaging techniques, or behavioral models, but these commonly require very invasive surgeries. This protocol presents a method for comparatively non-invasive application of compounds on the dura mater in mice and a suitable method for measuring headache-like tactile sensitivity using periorbital von Frey testing following dural stimulation. This method maintains the integrity of the dura and skull and reduces confounding effects from invasive techniques by injecting substances through a 0.65 mm modified cannula at the junction of unfused sagittal and lambdoid sutures. This preclinical model will allow researchers to investigate a wide range of dural stimuli and their role in the pathological progression of migraine, such as nociceptor activation, immune cell activation, vascular changes, and pain behaviors, all while maintaining injury-free conditions to the skull and meninges.
    Keywords brain ; cortex ; electrophysiology ; headache ; inflammation ; meninges ; migraine ; models ; neurons ; pathophysiology ; skull
    Language English
    Dates of publication 2021-0729
    Size p. e62867.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/62867
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Investigating Migraine-Like Behavior Using Light Aversion in Mice.

    Wang, Mengya / Mason, Bianca N / Sowers, Levi P / Kuburas, Adisa / Rea, Brandon J / Russo, Andrew F

    Journal of visualized experiments : JoVE

    2021  , Issue 174

    Abstract: Migraine is a complex neurological disorder characterized by headache and sensory abnormalities, such as hypersensitivity to light, observed as photophobia. Whilst it is impossible to confirm that a mouse is experiencing migraine, light aversion can be ... ...

    Abstract Migraine is a complex neurological disorder characterized by headache and sensory abnormalities, such as hypersensitivity to light, observed as photophobia. Whilst it is impossible to confirm that a mouse is experiencing migraine, light aversion can be used as a behavioral surrogate for the migraine symptom of photophobia. To test for light aversion, we utilize the light/dark assay to measure the time mice freely choose to spend in either a light or dark environment. The assay has been refined by introducing two critical modifications: pre-exposures to the chamber prior to running the test procedure and adjustable chamber lighting, permitting the use of a range of light intensities from 55 lux to 27,000 lux. Because the choice to spend more time in the dark is also indicative of anxiety, we also utilize a light-independent anxiety test, the open field assay, to distinguish anxiety from light-aversive behavior. Here, we describe a modified test paradigm for the light/dark and open field assays. The application of these assays is described for intraperitoneal injection of calcitonin gene-related peptide (CGRP) in two mouse strains and for optogenetic brain stimulation studies.
    MeSH term(s) Animals ; Behavior, Animal ; Calcitonin Gene-Related Peptide ; Mice ; Migraine Disorders ; Motor Activity ; Photophobia/etiology
    Chemical Substances Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
    Language English
    Publishing date 2021-08-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/62839
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Prolactin signaling modulates stress-induced behavioral responses in a preclinical mouse model of migraine.

    Mason, Bianca N / Kallianpur, Rohini / Price, Theodore J / Akopian, Armen N / Dussor, Gregory O

    Headache

    2021  Volume 62, Issue 1, Page(s) 11–25

    Abstract: Objective: The aim of this study was to determine if prolactin signaling modulates stress-induced behavioral responses in a preclinical migraine model.: Background: Migraine is one of the most complex and prevalent disorders. The involvement of sex- ... ...

    Abstract Objective: The aim of this study was to determine if prolactin signaling modulates stress-induced behavioral responses in a preclinical migraine model.
    Background: Migraine is one of the most complex and prevalent disorders. The involvement of sex-selective hormones in migraine pathology is highly likely as migraine is more common in women and its frequency correlates with reproductive stages. Prolactin has been shown to be a worsening factor for migraine. Normally prolactin levels are low; however levels can surge during stress. Dopamine receptor agonists, which suppress pituitary prolactin release, are an effective migraine treatment in a subset of patients. Previously, we showed that administration of prolactin onto the dura mater induces female-specific behavioral responses, suggesting that prolactin may play a sex-specific role in migraine.
    Methods: The effects of prolactin signaling were assessed using a preclinical migraine model we published recently in which behavioral sensitization is induced by repeated stress. Plasma prolactin levels were assessed in naïve and stressed CD-1 mice (n = 3-5/group) and transgenic mice with conditional deletion of the Prlr in Nav1.8-positive sensory neurons (Prlr conditional knock-out [CKO]; n = 3/group). To assess the contribution of prolactin release during stress, naïve or stressed male and female CD-1 mice were treated with the prolactin release inhibitor bromocriptine (2 mg/kg; n = 7-12/group) or vehicle for 5 days (8-12/group) and tested for facial hypersensitivity following stress. Additionally, the contribution of ovarian hormones in regulating the prolactin-induced responses was assessed in ovariectomized female CD-1 mice (n = 6-10/group). Furthermore, the contribution of Prlr activation on Nav1.8-positive sensory neurons was assessed. Naïve or stressed male and female Prlr CKO mice and their control littermates were tested for facial hypersensitivity (n = 8-9/group). Immunohistochemistry was used to confirm loss of Prlr in Nav1.8-positive neurons in Prlr CKO mice. The total sample size is n = 245; the full analysis sample size is n = 221.
    Results: Stress significantly increased prolactin levels in vehicle-treated female mice (39.70 ± 2.77; p < 0.0001). Bromocriptine significantly reduced serum prolactin levels in stressed female mice compared to vehicle-treated mice (-44.85 ± 3.1; p < 0.0001). Additionally, no difference was detected between female stressed mice that received bromocriptine compared to naïve mice treated with bromocriptine (-0.70 ± 2.9; p = 0.995). Stress also significantly increased serum prolactin levels in male mice, although to a much smaller extent than in females (0.61 ± 0.08; p < 0.001). Bromocriptine significantly reduced serum prolactin levels in stressed males compared to those treated with vehicle (-0.49 ± 0.08; p = 0.002). Furthermore, bromocriptine attenuated stress-induced behavioral responses in female mice compared to those treated with vehicle (maximum effect observed on day 4 post stress [0.21 ± 0.08; p = 0.03]). Bromocriptine did not attenuate stress-induced behavior in males at any timepoint compared to those treated with vehicle. Moreover, loss of ovarian hormones did not affect the ability of bromocriptine to attenuate stress responses compared to vehicle-treated ovariectomy mice that were stressed (maximum effect observed on day 4 post stress [0.29 ± 0.078; p = 0.013]). Similar to CD-1 mice, stress increased serum prolactin levels in both Prlr CKO female mice (27.74 ± 9.96; p = 0.047) and control littermates (28.68 ± 9.9; p = 0.041) compared to their naïve counterparts. There was no significant increase in serum prolactin levels detected in male Prlr CKO mice or control littermates. Finally, conditional deletion of Prlr from Nav1.8-positive sensory neurons led to a female-specific attenuation of stress-induced behavioral responses (maximum effect observed on day 7 post stress [0.32 ± 0.08; p = 0.007]) compared to control littermates.
    Conclusion: These data demonstrate that prolactin plays a female-specific role in stress-induced behavioral responses in this preclinical migraine model through activation of Prlr on sensory neurons. They also support a role for prolactin in migraine mechanisms in females and suggest that modulation of prolactin signaling may be an effective therapeutic strategy in some cases.
    MeSH term(s) Animals ; Behavior, Animal/drug effects ; Behavior, Animal/physiology ; Bromocriptine/administration & dosage ; Bromocriptine/pharmacology ; Disease Models, Animal ; Facial Pain/chemically induced ; Facial Pain/metabolism ; Facial Pain/physiopathology ; Female ; Hormone Antagonists/administration & dosage ; Hormone Antagonists/pharmacology ; Hyperalgesia/chemically induced ; Hyperalgesia/metabolism ; Hyperalgesia/physiopathology ; Male ; Mice ; Mice, Knockout ; Migraine Disorders/metabolism ; Migraine Disorders/physiopathology ; Ovariectomy ; Prolactin/antagonists & inhibitors ; Prolactin/drug effects ; Prolactin/metabolism ; Receptors, Prolactin/genetics ; Sex Characteristics ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Stress, Psychological/metabolism ; Stress, Psychological/physiopathology
    Chemical Substances Hormone Antagonists ; Receptors, Prolactin ; Bromocriptine (3A64E3G5ZO) ; Prolactin (9002-62-4)
    Language English
    Publishing date 2021-12-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 410130-3
    ISSN 1526-4610 ; 0017-8748
    ISSN (online) 1526-4610
    ISSN 0017-8748
    DOI 10.1111/head.14248
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Vascular actions of peripheral CGRP in migraine-like photophobia in mice.

    Mason, Bianca N / Wattiez, Anne-Sophie / Balcziak, Louis K / Kuburas, Adisa / Kutschke, William J / Russo, Andrew F

    Cephalalgia : an international journal of headache

    2020  Volume 40, Issue 14, Page(s) 1585–1604

    Abstract: Background: Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as ... ...

    Abstract Background: Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as preventative migraine drugs supports a peripheral site of action, such as the trigeminovasculature. Given the apparent disconnect between the importance of vasodilatory peptides in migraine and the prevailing opinion that vasodilation is an epiphenomenon, the goal of this study was to test whether vasodilation plays a role in calcitonin gene-related peptide-induced light aversive behavior in mice.
    Methods: Systemic mean arterial pressure and light aversive behavior were measured after intraperitoneal administration of calcitonin gene-related peptide and vasoactive intestinal peptide in wild-type CD1 mice. The functional significance of vasodilation was tested by co-administration of a vasoconstrictor (phenylephrine, endothelin-1, or caffeine) with calcitonin gene-related peptide to normalize blood pressure during the light aversion assay.
    Results: Both calcitonin gene-related peptide and vasoactive intestinal peptide induced light aversion that was associated with their effect on mean arterial pressure. Notably, vasoactive intestinal peptide caused relatively transient vasodilation and light aversion. Calcitonin gene-related peptide-induced light aversion was still observed even with normalized blood pressure. However, two of the agents, endothelin-1 and caffeine, did reduce the magnitude of light aversion.
    Conclusion: We propose that perivascular calcitonin gene-related peptide causes light-aversive behavior in mice by both vasomotor and non-vasomotor mechanisms.
    MeSH term(s) Animals ; Caffeine ; Calcitonin Gene-Related Peptide ; Endothelin-1/toxicity ; Mice ; Migraine Disorders ; Photophobia/chemically induced ; Vasoactive Intestinal Peptide
    Chemical Substances Endothelin-1 ; Vasoactive Intestinal Peptide (37221-79-7) ; Caffeine (3G6A5W338E) ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
    Language English
    Publishing date 2020-08-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 604567-4
    ISSN 1468-2982 ; 0333-1024
    ISSN (online) 1468-2982
    ISSN 0333-1024
    DOI 10.1177/0333102420949173
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Increased receptor activity-modifying protein 1 in the nervous system is sufficient to protect against autonomic dysregulation and hypertension.

    Sabharwal, Rasna / Mason, Bianca N / Kuburas, Adisa / Abboud, Francois M / Russo, Andrew F / Chapleau, Mark W

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

    2018  Volume 39, Issue 4, Page(s) 690–703

    Abstract: Calcitonin gene-related peptide (CGRP) can cause migraines, yet it is also a potent vasodilator that protects against hypertension. Given the emerging role of CGRP-targeted antibodies for migraine prevention, an important question is whether the ... ...

    Abstract Calcitonin gene-related peptide (CGRP) can cause migraines, yet it is also a potent vasodilator that protects against hypertension. Given the emerging role of CGRP-targeted antibodies for migraine prevention, an important question is whether the protective actions of CGRP are mediated by vascular or neural CGRP receptors. To address this, we have characterized the cardiovascular phenotype of transgenic nestin/hRAMP1 mice that have selective elevation of a CGRP receptor subunit in the nervous system, human receptor activity-modifying protein 1 (hRAMP1). Nestin/hRAMP1 mice had relatively little hRAMP1 RNA in blood vessels and intravenous injection of CGRP caused a similar blood pressure decrease in transgenic and control mice. At baseline, nestin/hRAMP1 mice exhibited similar mean arterial pressure, heart rate, baroreflex sensitivity, and sympathetic vasomotor tone as control mice. We previously reported that expression of hRAMP1 in all tissues favorably improved autonomic regulation and attenuated hypertension induced by angiotensin II (Ang II). Similarly, in nestin/hRAMP1 mice, hypertension caused by Ang II or phenylephrine was greatly attenuated, and associated autonomic dysregulation and increased sympathetic vasomotor tone were diminished or abolished. We conclude that increased expression of neuronal CGRP receptors is sufficient to induce a protective change in cardiovascular autonomic regulation with implications for migraine therapy.
    MeSH term(s) Animals ; Autonomic Nervous System Diseases/prevention & control ; Calcitonin Gene-Related Peptide/physiology ; Humans ; Hypertension/prevention & control ; Mice ; Mice, Transgenic ; Nervous System/chemistry ; Receptor Activity-Modifying Protein 1/metabolism ; Receptors, Calcitonin Gene-Related Peptide/metabolism
    Chemical Substances RAMP1 protein, human ; Receptor Activity-Modifying Protein 1 ; Receptors, Calcitonin Gene-Related Peptide ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
    Language English
    Publishing date 2018-01-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 604628-9
    ISSN 1559-7016 ; 0271-678X
    ISSN (online) 1559-7016
    ISSN 0271-678X
    DOI 10.1177/0271678X17751352
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: PACAP Induces Light Aversion in Mice by an Inheritable Mechanism Independent of CGRP.

    Kuburas, Adisa / Mason, Bianca N / Hing, Benjamin / Wattiez, Anne-Sophie / Reis, Alyssa S / Sowers, Levi P / Moldovan Loomis, Cristina / Garcia-Martinez, Leon F / Russo, Andrew F

    The Journal of neuroscience : the official journal of the Society for Neuroscience

    2021  Volume 41, Issue 21, Page(s) 4697–4715

    Abstract: The neuropeptides CGRP (calcitonin gene-related peptide) and PACAP (pituitary adenylate cyclase-activating polypeptide) have emerged as mediators of migraine, yet the potential overlap of their mechanisms remains unknown. Infusion of PACAP, like CGRP, ... ...

    Abstract The neuropeptides CGRP (calcitonin gene-related peptide) and PACAP (pituitary adenylate cyclase-activating polypeptide) have emerged as mediators of migraine, yet the potential overlap of their mechanisms remains unknown. Infusion of PACAP, like CGRP, can cause migraine in people, and both peptides share similar vasodilatory and nociceptive functions. In this study, we have used light aversion in mice as a surrogate for migraine-like photophobia to compare CGRP and PACAP and ask whether CGRP or PACAP actions were dependent on each other. Similar to CGRP, PACAP induced light aversion in outbred CD-1 mice. The light aversion was accompanied by increased resting in the dark, but not anxiety in a light-independent open field assay. Unexpectedly, about one-third of the CD-1 mice did not respond to PACAP, which was not seen with CGRP. The responder and nonresponder phenotypes were stable, inheritable, and not sex linked, although there was a trend for greater responses among male mice. RNA-sequencing analysis of trigeminal ganglia yielded hierarchical clustering of responder and nonresponder mice and revealed a number of candidate genes, including greater expression of the
    MeSH term(s) Animals ; Calcitonin Gene-Related Peptide/metabolism ; Calcitonin Gene-Related Peptide/pharmacology ; Female ; Male ; Mice ; Migraine Disorders/genetics ; Migraine Disorders/metabolism ; Photophobia/genetics ; Photophobia/metabolism ; Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism ; Pituitary Adenylate Cyclase-Activating Polypeptide/pharmacology ; Trigeminal Ganglion/metabolism
    Chemical Substances Adcyap1 protein, mouse ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
    Language English
    Publishing date 2021-04-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.2200-20.2021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: CGRP induces migraine-like symptoms in mice during both the active and inactive phases.

    Wattiez, Anne-Sophie / Gaul, Olivia J / Kuburas, Adisa / Zorrilla, Erik / Waite, Jayme S / Mason, Bianca N / Castonguay, William C / Wang, Mengya / Robertson, Bennett R / Russo, Andrew F

    The journal of headache and pain

    2021  Volume 22, Issue 1, Page(s) 62

    Abstract: Background: Circadian patterns of migraine attacks have been reported by patients but remain understudied. In animal models, circadian phases are generally not taken into consideration. In particular, rodents are nocturnal animals, yet they are most ... ...

    Abstract Background: Circadian patterns of migraine attacks have been reported by patients but remain understudied. In animal models, circadian phases are generally not taken into consideration. In particular, rodents are nocturnal animals, yet they are most often tested during their inactive phase during the day. This study aims to test the validity of CGRP-induced behavioral changes in mice by comparing responses during the active and inactive phases.
    Methods: Male and female mice of the outbred CD1 strain were administered vehicle (PBS) or CGRP (0.1 mg/kg, i.p.) to induce migraine-like symptoms. Animals were tested for activity (homecage movement and voluntary wheel running), light aversive behavior, and spontaneous pain at different times of the day and night.
    Results: Peripheral administration of CGRP decreased the activity of mice during the first hour after administration, induced light aversive behavior, and spontaneous pain during that same period of time. Both phenotypes were observed no matter what time of the day or night they were assessed.
    Conclusions: A decrease in wheel activity is an additional clinically relevant phenotype observed in this model, which is reminiscent of the reduction in normal physical activity observed in migraine patients. The ability of peripheral CGRP to induce migraine-like symptoms in mice is independent of the phase of the circadian cycle. Therefore, preclinical assessment of migraine-like phenotypes can likely be done during the more convenient inactive phase of mice.
    MeSH term(s) Animals ; Calcitonin Gene-Related Peptide ; Disease Models, Animal ; Female ; Humans ; Male ; Mice ; Migraine Disorders/chemically induced ; Motor Activity
    Chemical Substances Calcitonin Gene-Related Peptide (JHB2QIZ69Z)
    Language English
    Publishing date 2021-06-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2036768-5
    ISSN 1129-2377 ; 1129-2369
    ISSN (online) 1129-2377
    ISSN 1129-2369
    DOI 10.1186/s10194-021-01277-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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