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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Targeting CGRP via receptor antagonism and antibody neutralisation in two distinct rodent models of migraine-like pain

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. CGRP-dependent signalling pathways involved in mouse models of GTN- cilostazol- and levcromakalim-induced migraine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Poor social support and loneliness in chronic headache: Prevalence and effect modifiers

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Vestibular migraine: diagnostic criteria1

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. CGRP-dependent signalling pathways involved in mouse models of GTN- cilostazol- and levcromakalim-induced migraine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Paracetamol use during pregnancy - a call for precautionary action

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

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INTRODUCTION: Rodent disease models can play an indispensable role in drug development. Confirming that translationally-relevant disease mechanisms are engaged in such models is a crucial facet of this process. Accordingly, we have validated the role of calcitonin gene-related peptide signaling in a mouse model of glyceryl trinitrate-provoked migraine-like pain and a spontaneous rat model of migraine-like pain by assessing their pharmacological responsiveness to the small molecule calcitonin gene-related peptide receptor antagonist olcegepant, and the humanised monoclonal calcitonin gene-related peptide antibody ALD405.

METHODS: Cutaneous sensitivity to hind paw, and periorbital mechanical stimulation were used as surrogate markers of activation of relevant pain pathways in each respective model. Separate experiments were performed to identify the time-course of treatment response to olcegepant (1 mg/kg i.p.) and ALD405 (10 mg/kg i.p.).

RESULTS: Olcegepant and ALD405 significantly alleviated cutaneous mechanical hypersensitivity in both models compared with corresponding control treatments (saline and IgG control antibody respectively). As expected, the duration of anti-nociceptive action obtained with ALD405 was considerably longer than that associated with olcegepant. Surprisingly, in the spontaneous rat model the onset of action of ALD405 occurred within just 4 hours after administration.

DISCUSSION: The current data clearly show that calcitonin gene-related peptide-mediated signaling is critically involved in the manifestation of cutaneous hypersensitivity in distinct rodent models of migraine-like pain and emphasise their translational relevance. Moreover, the unexpected rapidity of onset observed for ALD405 supports i) a probable site of action outside the blood-brain barrier, and ii) a potential clinical utility of specific monoclonal calcitonin gene-related peptide antibodies in the abortive treatment of migraine.

OriginalsprogEngelsk
TidsskriftCephalalgia : an international journal of headache
Vol/bind39
Udgave nummer14
Sider (fra-til)1827-1837
Antal sider11
ISSN0333-1024
DOI
StatusUdgivet - 2019

ID: 58916792