CGRP receptor antagonist MK-8825 attenuates cortical spreading depression induced pain behavior.
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 ana...
| Publicado en: | Cephalalgia Vol. 39; no. 3; pp. 354 - 366 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Sage Publications Inc.
Mar2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=135307859&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 135307859 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03331024 F05 jtl: Cephalalgia issn: 03331024 maglogo: Y pubinfo: dt: Mar2019 vid: 39 iid: 3 pid: 344 pub: Sage Publications Inc. place: Thousand Oaks, California artinfo: ui: 135307859 135307859 NLM28971699 135307859 10.1177/0333102417735845 NLM28971699 135307859 ppf: 354 ppct: 12 formats: tig: atl: CGRP receptor antagonist MK-8825 attenuates cortical spreading depression induced pain behavior. aug: au: Filiz, Aslı Tepe, Nermin Eftekhari, Sajedeh Boran, H. Evren Dilekoz, Ergin Edvinsson, Lars Bolay, Hayrunnisa affil: Department of Neurology and Algology, Gazi University Medical School, Besevler, Ankara, Turkey sug: subj: Pyridines Therapeutic Use Hydrocarbons Therapeutic Use Pain Measurement Evoked Potentials Drug Effects Pain Drug Therapy Cerebrovascular Circulation Drug Effects Rats Pain Physiopathology Pyridines Pharmacodynamics Male Evoked Potentials Physiology Cerebral Cortex Physiopathology Hydrocarbons Pharmacodynamics Animals Cerebrovascular Circulation Physiology Pain Measurement Methods Cerebral Cortex Drug Effects Dose-Response Relationship, Drug Male ab: 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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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