A CGRP receptor antagonist and dihydroergotamine (DHE) reduce migraine-like behaviors in a rat multisymptom model of migraine (Neuroscience 2012) - Aug 20, 2012 - Presentation time: Saturday, Oct 13, 2012, 2:00 PM - 3:00 PM; The CGRP receptor antagonist MK-8825 was given ip 30mg/kg 60 min prior to IS application; DHE was given iv 100 microg/kg 30-60 min prior to IS on days 1-4 and 1mg/kg sc on day 5; Neither drug altered activity, reduced light or sound avoidance, but both drugs had effects in the allodynia task, reducing the latency to the first grooming event
Preclinical-animal • Migraine
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Neuroscience, Oct 13-17, 2012
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67.14/V1
Animal models of migraine have been hampered by limitations that reduce their face validity, such as electrophysiology that does not assess nociceptive behaviors, or behavioral models relying on orofacial testing in restrained subjects. In humans, IHS criteria used for migraine diagnosis are based on behavioral changes including photophobia, phonophobia, and avoidance of routine activity. In addition, facial allodynia occurs during or just after most migraine attacks. This study aimed to determine whether migraine-like behaviors that develop after application of inflammatory soup (IS) containing 1mM histamine, serotonin, bradykinin and 0.1 mM PGE2, pH 5.5 to the dura are reduced by treatment with drugs that are known to reduce migraine. Female Sprague-Dawley rats were fitted with an indwelling dural cannulae placed over the occipital cortex. Baseline behavioral testing was conducted prior to surgery and 7 days post-surgery. Groups of rats were then treated with IS repeated 3 times/week for a total of 8 applications to simulate chronic migraine. Behavioral testing was conducted during and after dural stimulation in a modified Force-Plate Actimeter (BaSI) apparatus, providing detailed, quantitative measurements of locomotor activity that was modified to allow testing of light and sound avoidance. Conditions in the behavioral arena were modified in five-minute periods with 1) no external light or sound, 2) illumination of one side of the chamber to 400 lux, 3) no external light or sound, and 4) 90 dB white noise delivered to one side of the chamber. Following testing in the chamber, facial allodynia was assessed by applying a metered water spray to the rats’ faces and observing latency to groom, time spend grooming, and the number of grooming swipes. Two drug classes that have demonstrated anti-migraine effectiveness were tested in this model. The CGRP receptor antagonist MK-8825 was given ip 30 mg/kg 60 min prior to IS application. DHE was given iv 100 microg/kg 30-60 min prior to IS on days 1-4 and 1 mg/kg sc on day 5. Neither drug altered activity, reduced light or sound avoidance, but both drugs had significant effects in the allodynia task, reducing the latency to the first grooming event. These data confirm that the behavioral rodent migraine model is sensitive to drugs used to treat migraine.
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