Nociceptive behaviors were induced by electrical stimulation of the dura mater surrounding the superior sagittal sinus in conscious adult rats and reduced by morphine and rizatriptan benzoate

Background To facilitate understanding the locus and mechanism of action of antimigraine preventives, we examined the effect of topiramate on trigeminocervical activation in the cat. Methods Cats were anesthetized and physiologically monitored. Electrical stimulation of the superior sagittal sinus activated nociceptive trigeminovascular afferents. Extracellular recordings were made from neurons in the trigeminocervical complex. Results Microiontophoretically delivered topiramate, applied locally at the second order synapse of the trigeminovascular system in the trigeminocervical complex, produced significant inhibition of L-glutamate-evoked firing of neurons only at the highest microiontophoretic currents (27 ± 7% at −160 nA; p < 0.05, n = 14 cells), but did not inhibit firing of these neurons evoked by stimulation of the craniovascular afferents (2 ± 5%, p = 0.762, n = 13 cells). In contrast, systemically administered topiramate (30 mg/kg intravenously) partly inhibited this firing (32 ± 10% at 15 min; F5,35 = 3.5, p < 0.05, n = 8 cats). After this systemic administration, profound inhibition (70 ± 10%, p < 0.001, n = 7) of L-glutamate-evoked firing of cells in the trigeminocervical complex at the second order synapse of the trigeminovascular system was observed. Conclusions These data suggest that topiramate acts outside of the trigeminocervical complex in the cat. Determining the sites of action of preventive antimigraine treatments is crucial to developing laboratory models for the development of new therapeutics, and may vary between species.

Download Full-text

Activation of the Trigeminovascular System by Mechanical Distension of the Superior Sagittal Sinus in The Cat

Cephalalgia ◽

10.1046/j.1468-2982.1992.1203133.x ◽

1992 ◽

Vol 12 (3) ◽

pp. 133-136 ◽

Cited By ~ 67

Author(s):

Holger Kaube ◽

Karen L Hoskin ◽

Peter J Goadsby

Keyword(s):

Spinal Cord ◽

Electrical Stimulation ◽

Vessel Wall ◽

Superior Sagittal Sinus ◽

Single Units ◽

Vascular Disorder ◽

Trigeminovascular System ◽

Sagittal Sinus ◽

Cat Model ◽

Stimulation Of

Distension of dural sinuses in man produces migraine-like pain. In eight a-chloralose anaesthetized cats mechanical distension of the superior sagittal sinus with a small intraluminal device was used to activate single units in the dorsolateral C2 spinal cord. Units in this region have been shown to respond to electrical stimulation of the superior sagittal sinus in the cat model. Linked responses to mechanical dilatation could only be obtained with very rapid stretching stimuli or high amplitudes of distension of the vessel. Lower thresholds for transduction of distension in the vessel wall may depend on transferral to the dura or biochemical or neural pre-sensitization of the superior sagittal sinus. These data are consistent with the view that migraine is not primarily a vascular disorder but requires at least humoral or neural facilitation.

Download Full-text

Experimental Migraine Models and Their Relevance in Migraine Therapy

Cephalalgia ◽

10.1111/j.1468-2982.2005.01082.x ◽

2006 ◽

Vol 26 (6) ◽

pp. 642-659 ◽

Cited By ~ 31

Author(s):

U Arulmani ◽

S Gupta ◽

A Maassen VanDenBrink ◽

D Centurión ◽

CM Villalón ◽

...

Keyword(s):

Electrical Stimulation ◽

Trigeminal Ganglion ◽

In Vitro Models ◽

In Vivo Model ◽

Trigeminal System ◽

Sagittal Sinus ◽

Migraine Pathophysiology ◽

Stimulation Of

Although the understanding of migraine pathophysiology is incomplete, it is now well accepted that this neurovascular syndrome is mainly due to a cranial vasodilation with activation of the trigeminal system. Several experimental migraine models, based on vascular and neuronal involvement, have been developed. Obviously, the migraine models do not entail all facets of this clinically heterogeneous disorder, but their contribution at several levels (molecular, in vitro, in vivo) has been crucial in the development of novel antimigraine drugs and in the understanding of migraine pathophysiology. One important vascular in vivo model, based on an assumption that migraine headache involves cranial vasodilation, determines porcine arteriovenous anastomotic blood flow. Other models utilize electrical stimulation of the trigeminal ganglion/nerve to study neurogenic dural inflammation, while the superior sagittal sinus stimulation model takes into account the transmission of trigeminal nociceptive input in the brainstem. More recently, the introduction of integrated models, namely electrical stimulation of the trigeminal ganglion or systemic administration of capsaicin, allows studying the activation of the trigeminal system and its effect on the cranial vasculature. Studies using in vitro models have contributed enormously during the preclinical stage to characterizing the receptors in cranial blood vessels and to studying the effects of several putative antimigraine agents. The aforementioned migraine models have advantages as well as some limitations. The present review is devoted to discussing various migraine models and their relevance to antimigraine therapy.

Download Full-text