Topiramate Inhibits Trigeminovascular Neurons in the Cat

• Published in: Cephalalgia 2004-12, Vol.24 (12), p.1049-1056
• Main Authors: Storer, RJ, Goadsby, PJ
• Format: Article
• Language: English
• Subjects: Animals; Cats; cluster headache; Dose-Response Relationship, Drug; Fructose - analogs & derivatives; Fructose - pharmacology; migraine; Neuroprotective Agents - pharmacology; preventive; Trigeminal Nerve - drug effects; Trigeminal Nerve - metabolism; Trigeminal Nuclei - drug effects; Trigeminal Nuclei - metabolism; trigeminovascular
• ISSN: 0333-1024; 1468-2982
• DOI: 10.1111/j.1468-2982.2004.00767.x

To facilitate understanding the action of antimigraine preventives the effect of topiramate on trigeminocervical activation in the cat was examined. Animals (n = 7) were anaesthetized and physiologically monitored. The superior sagittal sinus (SSS) was stimulated to produce a model of trigeminovascular nociceptive activation. Cumulative dose-response curves were constructed for the effect of topiramate at doses of 3, 5, 10, 30 and 50 mg/kg on SSS-evoked firing of trigeminocervical neurons. Topiramate reduced SSS evoked firing in a dose-dependent fashion. The maximum effect was seen over 30 min for the cohort taken together. At 3 mg/kg firing was reduced by 36 ± 13% (mean ± SEM) after 15 min. At 5 and 50 mg/kg firing was reduced by 59 ± 6% and 65 ± 14%, respectively, after 30 min. Inhibition of the trigeminocervical complex directly, or neurons that modulate sensory input, are plausible mechanisms for the action of preventives in migraine.