Migraine, Capsaicin-induced Dermal Blood Flow (CIDBF)

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BIOLOGICAL INFORMATION
BACKGROUND INFORMATION
The capsaicin-induced dermal blood flow (CIDBF) is a model to mimic the mechanism of migraine triggered by the calcitonin gene-related peptide (CGRP) associated pathways. Capsaicin induces CGRP release and thereby vasodilatation and increased dermal blood flow (DBF), and can be detected by the Laser Doppler Imager (LDI). The relative blood flow change to baseline served as the endpoints and the efficacy levels in the CIDBF model. Ubrogepant (5 mg/kg IV) is a positive control that can alleviate >50% of the relative blood flow changes.
ORGANISM
Rat
ASSAY INFORMATION
ASSAY TYPE
In Vivo
TESTING INFORMATION
PROCEDURE SUMMARY
Groups of 8 male Lewis rats at 8 weeks of age are used. Rats are stably anesthetized with pentobarbital (30 mg/kg, IP) and placed in the supine position on a temperature-controlled blanket and fitted with a nose cone connected to 2.5% isoflurane/oxygen gas anesthesia. On the shaved abdomen, two rubber O-rings are placed on each side of the abdomen. Test substance and vehicle are administered to animals by a single intravenous (IV) injection 10 minutes before topical capsaicin stimulation. Following measurement of the basal dermal blood flow (DBF) by Laser Doppler Imager (Moor, LDI2-IR) in the abdominal skin, eight (8) microliter of capsaicin is added to each O-ring. Consecutive measurements of DBF are taken for another 25 minutes. % DBF increase over the baseline is calculated in each animal. Statistical analysis is performed by Repeat Measure two-way ANOVA followed by Dunnett's test comparing to the vehicle group; p<0.05 is considered significant. Suggested Testing: n=8/group (study design dependent). Analgesic effects assessed at an initial dose of 100 mg/kg. Dosing volume at 10 mL/kg.
CRITERIA FOR SIGNIFICANCE
The blood flow change relative to baseline ≥ 50% is considered as a successful induction in vehicle control group.
TURNAROUND TIME
STANDARD
50 Days
CLINICAL RELEVANCE
THERAPEUTIC AREA
CNS/Addiction/Pain
ADDITIONAL INFORMATION
BRAND
PDS
TESTING LOCATION
Taiwan - Taipei
OTHER INFORMATION
We will readily accommodate client-specified alterations. These studies are performed at our AAALAC accredited BSL-1 laboratory in Taipei, Taiwan. All aspects of this work are performed in general accordance with the Guide for the Care and Use of laboratory animals (National Academy Press, Washington, DC, 2011). The study protocol was approved by the Pharmacology Discovery Services IACUC and is performed with the oversight of veterinarians to assure the humane treatment of laboratory animals.

 

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