Inhibitory effect of chronic oral treatment with fluoxetine on capsaicin-induced external carotid vasodilatation in anaesthetised dogs

• Published in: Cephalalgia 2015-10, Vol.35 (12), p.1041-1053
• Main Authors: Muñoz-Islas, Enriqueta, González-Hernández, Abimael, Lozano-Cuenca, Jair, Ramírez-Rosas, Martha Beatríz, Medina-Santillán, Roberto, Centurión, David, MaassenVanDenBrink, Antoinette, Villalón, Carlos M
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Blood Flow Velocity - drug effects; Blood Flow Velocity - physiology; Blood Pressure - drug effects; Blood Pressure - physiology; Capsaicin - administration & dosage; Carotid Artery, Internal - drug effects; Carotid Artery, Internal - physiology; Dogs; Drug Interactions; Fluoxetine - administration & dosage; Heart Rate - drug effects; Heart Rate - physiology; Male; Serotonin Uptake Inhibitors - administration & dosage; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - administration & dosage
• ISSN: 0333-1024; 1468-2982
• DOI: 10.1177/0333102414566818

Background During migraine, capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception. Moreover, 5-HT is involved in the pathophysiology of migraine and depression. Interestingly, some limited lines of evidence suggest that fluoxetine may be effective in migraine prophylaxis, but the underlying mechanisms are uncertain. Hence, this study investigated the canine external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine before and after acute and chronic oral treatment with fluoxetine. Methods Forty-eight vagosympathectomised male mongrel dogs were prepared to measure blood pressure, heart rate and external carotid blood flow. The thyroid artery was cannulated for infusions of agonists. In 16 of these dogs, a spinal cannula was inserted (C1–C3) for infusions of 5-HT. Results The external carotid vasodilator responses to capsaicin, α-CGRP and acetylcholine remained unaffected after intracarotid or i.v. fluoxetine. In contrast, the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine, were inhibited after chronic oral treatment with fluoxetine (300 µg/kg; for 90 days) or intrathecal 5-HT. Conclusions Chronic oral fluoxetine inhibited capsaicin-induced external carotid vasodilatation, and this inhibition could partly explain its potential prophylactic antimigraine action.