22 FEB 2024
Pharmacology Discovery Services (PDS), a partner lab of Eurofins Discovery, offers a novel pathway to discovering therapeutic relief for migraine headaches. Migraines are a neurological disorder affecting approximately 12% of the global populace1.
Migraines are characterized by recurring, pulsating headaches typically affecting one side of the head, and often include nausea and sensitivity to light and sound. The severity and duration of migraines, along with their frequent onset due to stress, hormonal changes, or lack of sleep, present a significant impact to quality of life2 for the millions of people who suffer.
In the complex landscape of migraine pathophysiology, the calcitonin gene-related peptide (CGRP) has emerged as a key player in these headaches. Research over the past three decades indicates that increased CGRP levels lead to inflammation and dilation of blood vessels in the brain, causing migraine pain and associated symptoms. Drugs targeting CGRP or its receptors, known as CGRP inhibitors, present a promising therapeutic approach. These inhibitors have shown more effectiveness in reducing migraine frequency and severity compared to previous therapies, with fewer side effects3,4.
Our novel diagnostic tool, Capsaicin-induced Dermal Blood Flow (CIDBF), uses the TRPV1 receptor agonist, capsaicin, to measure the therapeutic potential of drugs for migraines. By applying a small amount of capsaicin topically, changes in dermal blood flow can be evaluated using techniques like laser Doppler imaging. This model facilitates the examination of the role of CGRP and other neuropeptides in conditions such as migraines, providing crucial insights into the therapeutic efficacy of vasodilation and blood flow modulation interventions5.
At PDS, we offer CIDBF measurement using male Lewis rats. Following measurement of the basal dermal blood flow (DBF) by Laser Doppler Imager in the abdominal skin of the test animal, capsaicin at 8 μL/site, is applied on two sites within two rubber O-rings, 3 mm in diameter each, placed on each side of the shaved abdomen under anesthesia. The standard offered positive control, ubrogepant at 5 mg/kg, a clinically approved drug, is administered by a single intravenous injection 10 minutes before topical capsaicin stimulation. To meet therapeutic needs the team can tailor the treatment time point, dosage, administration route, and vehicle. Consecutive DBF measurements are taken for another 25 minutes, the standard endpoint. The percentage of DBF increase over the baseline is calculated in each animal and provided as standard readout. Also available upon request are optional endpoints, including terminal plasma, brain, or other tissue collection.
Figure 1. Representative data of migraine model using CIDBF. Capsaicin was applied to euthanized animals as described. Ubrogepant, at 5, 1, 0.5, and 0.1 mg/kg, is administered by a single intravenous injection 10 min before topical capsaicin stimulation. DBF measurement by Laser Doppler Imager was conducted every 5 min. from 0 min. (pre-capsaicin) until 25 min. after topical capsaicin stimulation.
Our laboratory staff has an average of 15 years of experience in conducting in vivo pharmacology studies. Relative husbandry and animal handling comply with the species-specific recommendations of the Guide for the Care and Use of Laboratory Animals (2011), a respected scientific resource compiled by a committee of recognized experts, and are conducted within the facility accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), an international nonprofit that promotes humane treatment of animals in science.
| Translational Pain In Vivo Model | ||
|---|---|---|
| Model Name | Item Number | TAT |
| Migraine, Capsaicin-induced Dermal Blood Flow (CIDBF) | 501000 | 50 days |
Resources
- Technical Sheet
- Migraine Model for In Vivo Studies
- Steiner TJ, Stovner LJ. Global epidemiology of migraine and its implications for public health and health policy. Nat Rev Neurol. 2023 Feb;19(2):109-117.
- Peters GL. Migraine overview and summary of current and emerging treatment options. Am J Manag Care. 2019 Jan;25(2 Suppl):S23-S34.
- Iyengar S, Johnson KW, Ossipov MH, Aurora SK. CGRP and the Trigeminal System in Migraine. Headache. 2019 May;59(5):659-681.
- Edvinsson L. CGRP and migraine: from bench to bedside. Rev Neurol (Paris). 2021 Sep;177(7):785-790.
- Buntinx L, Vermeersch S, de Hoon J. Development of anti-migraine therapeutics using the capsaicin-induced dermal blood flow model. Br J Clin Pharmacol. 2015 Nov;80(5):992-1000.
