scholarly journals EHMTI-0018. CGRP receptor antagonists attenuate pain behavior induced by cortical spreading depression in freely moving rats

2014 ◽  
Vol 15 (S1) ◽  
Author(s):  
A Filiz ◽  
N Tepe ◽  
E Boran ◽  
E Sajedeh ◽  
E Lars ◽  
...  
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Pain Behavior ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Freely Moving Rats ◽  
Cgrp Receptor Antagonists ◽  
Freely Moving

CGRP receptor antagonist MK-8825 attenuates cortical spreading depression induced pain behavior

Cephalalgia ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 354-365 ◽  
Author(s):  
Aslı Filiz ◽  
Nermin Tepe ◽  
Sajedeh Eftekhari ◽  
H Evren Boran ◽  
Ergin Dilekoz ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Pain Behavior ◽  
Reticular Nucleus ◽  
Cgrp Receptor ◽  
Freely Moving Rats ◽  
Behavioral Studies ◽  
Freely Moving ◽  
Cgrp Receptor Antagonist

Background and objective The present study aimed to investigate the effects of selective calcitonin gene related peptide (CGRP) receptor antagonist (MK-8825) on cortical spreading depression (CSD) induced pain behavior and anxiety in freely-moving rats, and neuronal activation in the correlated anatomical regions. Methods CSD was induced while keeping all meningeal layers and BBB intact and MK-8825 was administered in two different doses. Regional cerebral blood flow (rCBF), arterial pressure and DC shift were recorded. Behavioral studies were conducted in freely-moving rats. Spontaneous behavior, mechanical allodynia, ultrasonic vocalization, and anxiety were evaluated. Immunohistochemistry of c-fos, CGRP, calcitonin receptor like-receptor (CLR) and receptor activity modifying protein 1 (RAMP1) were studied. Results MK-8825 did not block DC shifts in the cerebral cortex and accompanied hemodynamic response. CSD significantly induced freezing and grooming behavior in freely-moving rats. MK-8825 reversed increased episodes of freezing, grooming, wet dog shake and head shake behavior. MK-8825 increased CSD-induced reductions in von Frey thresholds, but did not change elevated plus maze results. MK-8825 blocked c-fos induction by CSD in the brainstem trigeminal nucleus caudalis (TNC) and reticular nucleus of thalamus (TRN) but not in the amygdala. Immunofluorescence analysis showed no co-localization of CGRP, CLR or RAMP1 with c-fos positive cells. Conclusion CGRP receptor antagonist MK-8825 dose dependently attenuated CSD-induced trigeminal nerve mediated pain response without altering CSD waves and accompanied rCBF response. While blocking TNC activation, MK-8825 did not exert any effect on amygdala and anxiety behavior. CGRP receptor antagonists may also modulate thalamo-cortical gating.

scholarly journals Evaluation of cutaneous allodynia following induction of cortical spreading depression in freely moving rats

Cephalalgia ◽  
2011 ◽  
Vol 31 (10) ◽  
pp. 1090-1100 ◽  
Author(s):  
Beatriz Fioravanti ◽  
Aimen Kasasbeh ◽  
Rebecca Edelmayer ◽  
David P Skinner Jr ◽  
Jed A Hartings ◽  
...  
Keyword(s):  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Occipital Cortex ◽  
Underlying Mechanism ◽  
Bioelectrical Activity ◽  
Freely Moving Rats ◽  
Cutaneous Allodynia ◽  
The Face ◽  
Freely Moving ◽  
Sustained Activation

Background: Cortical spreading depression (CSD) is a wave of depolarization followed by depression of bioelectrical activity that slowly propagates through the cortex. CSD is believed to be the underlying mechanism of aura in migraine; however, whether CSD can elicit pain associated with migraine headache is unclear. Methods: Awake, freely moving rats were monitored for both CSD events and behavioral responses resulting from dural-cortical pinprick and/or KCl injection to the occipital cortex. Results: We observed tactile allodynia of the face and hindpaws, as well as enhanced Fos expression within the trigeminal nucleus caudalis (TNC) following CSD induced by KCl injection into the cortex, but not by pinprick. Application of KCl onto the dura elicited cutaneous allodynia and increased Fos staining in the TNC but did not elicit CSD events. Conclusions: These data suggest that sustained activation of trigeminal afferents that may be required to establish cutaneous allodynia may not occur following CSD events in normal animals.

Does single cortical spreading depression elicit pain behaviour in freely moving rats?

Cephalalgia ◽  
2010 ◽  
Vol 30 (10) ◽  
pp. 1195-1206 ◽  
Author(s):  
Didem Akcali ◽  
Aslihan Sayin ◽  
Yildirim Sara ◽  
Hayrunnisa Bolay
Keyword(s):  
Cortical Spreading Depression ◽  
Animal Studies ◽  
Spreading Depression ◽  
Video Camera ◽  
Human Beings ◽  
Freely Moving Rats ◽  
Migraine Pathogenesis ◽  
Freely Moving ◽  
Cephalic Pain ◽  
Analysis System

Introduction: Behavioural animal studies are critical, particularly to translate results to human beings. Cortical spreading depression (CSD) has been implicated in migraine pathogenesis. We aimed to investigate the effects of CSD on the behaviour of freely moving rats, since available CSD models do not include awake animals. Materials and methods: We developed a new model to induce single CSD by applying topical N-methyl-D-aspartate (NMDA) and employed a combination of an automated behavioural analysis system, video camera and ultrasonic vocalisation (USV) calls for the first time. Electrocorticograms were also studied during CSD in freely moving rats. Behaviour associated with cephalic pain was assessed in a group of rats that received sumatriptan. Cortical c-fos immunoreactivity was performed in order to confirm CSD. Results: NMDA induced single CSD in ipsilateral cortex, evoked freezing behaviour ( P < 0.01) and increased the number of wet dog shakes (WDS; P < 0.01). Grooming, locomotion, eating, drinking, and circling were not significantly altered among groups. Ultrasonic vocalisations compatible with pain calls (22–27 kHz) were only detected in 3 out of 25 rats. Sumatriptan did not significantly reduce the freezing behaviour. CSD induced significant c-fos expression in ipsilateral cerebral cortex and amygdala ( P < 0.01). Conclusions: CSD induces freezing behaviour by invoking anxiety/fear via amygdala activation in freely-moving rats. Single CSD is unlikely to lead to severe pain in freely-moving rats, though the development of mild or vague pain cannot be excluded. The relevance of rat behavioural responses triggered by CSD to migraine symptoms in humans needs further evaluation.

The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates. Part 1

2012 ◽  
Vol 22 (14) ◽  
pp. 4723-4727 ◽  
Author(s):  
Xiaojun Han ◽  
Rita L. Civiello ◽  
Charles M. Conway ◽  
Deborah A. Cook ◽  
Carl D. Davis ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists

scholarly journals Effect of Calcitonin Gene-Related Peptide Receptor Antagonists on Migraine Treatment: A Meta-Analysis

2021 ◽  
Author(s):  
Jiyoung Kim ◽  
Kyoungjune Pak ◽  
Gha-Hyun Lee ◽  
Jae Wook Cho ◽  
Hyun-Woo kim
Keyword(s):  
Meta Analysis ◽  
Calcitonin Gene Related Peptide ◽  
Migraine Treatment ◽  
Acute Migraine ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists ◽  
Acute Migraine Treatment

Abstract Background: The pathophysiology of migraine has been researched incessantly, and it has been suggested that calcitonin gene-related peptide (CGRP) is associated with migraine attacks. CGRP receptor blockers are attracting attention for migraine prevention and treatment of acute episodes, and CGRP receptor antagonists have been shown to be effective in treating acute migraine headaches. This meta-analysis aimed to assess the effect of available CGRP receptor antagonists, focusing on their therapeutic doses for acute migraine treatment.Methods: We performed a systematic search of MEDLINE (from inception to March 2021) and EMBASE (from inception to March 2021) for English publications using the keywords “migraine” and “Calcitonin gene-related peptide,” limited to human studies.Results: Five studies that focused on examining the effects of CGRP receptor antagonists on acute migraine treatment met the eligibility criteria for this meta-analysis. The pooled analysis demonstrated that the CGRP receptor antagonist improved freedom from pain (OR=2.066, 95% confidence interval [CI] 1.766–2.418, I2=0%), absence of bothersome symptoms (OR=1.606, 95% CI=1.408–1.830, I2=0%), pain relief (OR=1.791, 95% CI=1.598–2.008, I2=0%), and freedom from nausea (OR=1.361, 95% CI=1.196–1.548, I2=0%), significantly more than the placebo. Conclusions: CGRP receptor antagonists are effective for acute migraine treatment and are expected to be used clinically as emerging therapeutic agents.

Quinine analogs as non-peptide calcitonin gene-related peptide (CGRP) receptor antagonists

1997 ◽  
Vol 7 (20) ◽  
pp. 2673-2676 ◽  
Author(s):  
Robert A. Daines ◽  
Kelvin K.C. Sham ◽  
Jack J. Taggart ◽  
William D. Kingsbury ◽  
James Chan ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Cgrp Receptor ◽  
Receptor Antagonists ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Receptor Antagonists
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