Topiramate in the treatment of migraine: A kainate (glutamate) receptor antagonist within the trigeminothalamic pathway

Andreou, Anna P.; Goadsby, PJ

doi:10.1177/0333102411418259

Cited by 78 publications

(59 citation statements)

References 71 publications

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“…These observations are consistent with the likely mechanisms of action of topiramate to reduce CNS excitability. Topiramate attenuates voltage-gated sodium and calcium channels, blocks α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/ kainate receptor activity, and enhances the γ-aminobutyric acid type A (GABA A ) inhibitory chloride channels (68,69). These properties together are likely to strongly interfere with CSD propagation (20).…”

Section: Discussionmentioning

confidence: 99%

Increased susceptibility to cortical spreading depression in an animal model of medication-overuse headache

Green

Felice

et al. 2013

Cephalalgia

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Objective The objective of this article is to evaluate electrically evoked thresholds for cortical spreading depression (CSD) and stress-induced activation of trigeminal afferents in a rat model of medication-overuse headache (MOH). Methods Sumatriptan or saline was delivered subcutaneously by osmotic minipump for six days to Sprague-Dawley rats. Two weeks after pump removal, animals were anesthetized and recording/stimulating electrodes implanted. The animals were pretreated with vehicle or topiramate followed by graded electrical stimulation within the visual cortex. CSD events were identified by decreased EEG amplitude and DC potential shift. Additional unanesthetized sumatriptan or saline-pretreated rats were exposed to bright light environmental stress and periorbital and hindpaw withdrawal thresholds were measured. Following CSD stimulation or environmental stress, immunohistochemical staining for Fos in the trigeminal nucleus caudalis (TNC) was performed. Results Sumatriptan pre-exposure significantly decreased electrical stimulation threshold to generate a CSD event. Topiramate normalized the decreased CSD threshold as well as stress-induced behavioral withdrawal thresholds in sumatriptan-treated rats compared to saline-treated animals. Moreover, CSD and environmental stress increased Fos expression in the TNC of sumatriptan-treated rats, and these effects were blocked by topiramate. Environmental stress did not elicit cutaneous allodynia or elevate TNC Fos expression in saline-treated rats. Conclusions A previous period of sumatriptan exposure produced long-lasting increased susceptibility to evoked CSD and environmental stress-induced activation of the TNC that was prevented by topiramate. Lowered CSD threshold, and enhanced consequences of CSD events (increased activation of TNC), may represent an underlying biological mechanism of MOH related to triptans.

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Section: Discussionmentioning

confidence: 99%

Increased susceptibility to cortical spreading depression in an animal model of medication-overuse headache

Green

Felice

et al. 2013

Cephalalgia

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“…Specifically, topiramate's mechanism of kainite receptor antagonism has been identified in the glutamate system as part of the trigeminothalamic pathway. 41 Glutamate is an important excitatory amino acid and believed to be involved in the pathophysiology of migraine and other pain disorders. Glutamate related receptors such as the N-methyl-D-aspartate (NMDA) receptor are located in key pain processing structures, including the dorsal root ganglion, spinal cord, and thalamus.…”

Section: Anti-epileptic Drugsmentioning

confidence: 99%

Cervicogenic Headache

Cooper

Masih

2015

Headache and Migraine Biology and Management

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“…Conversely, selective activation of GluK1 receptors with a willardiine analog attenuated calcitonin gene related peptide-induced vasodilation caused by dural stimulation, an experimental paradigm that mimics some of the neurogenic processes thought to occur during migraine (Andreou et al, 2009). The efficacy of topiramate, an anticonvulsant, in prevention of migraines also was recently proposed to arise from antagonistic actions on KAR-driven signaling in the trigeminovascular pathways (Andreou and Goadsby, 2011). Among other pharmacological activities, topiramate appears to selectively reduce signaling through GluK1-containing KARs through mechanisms that are not well understood (Gryder and Rogawski, 2003;Braga et al, 2009).…”

Section: Kars As Targets In Animal Models Of Pain and Clinical Studiesmentioning

confidence: 99%

Kainate Receptor Signaling in Pain Pathways

Bhangoo

Swanson

2012

Mol Pharmacol

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Receptors and channels that underlie nociceptive signaling constitute potential sites of intervention for treatment of chronic pain states. The kainate receptor family of glutamate-gated ion channels represents one such candidate set of molecules. They have a prominent role in modulation of excitatory signaling between sensory and spinal cord neurons. Kainate receptors are also expressed throughout central pain neuraxis, where their functional contributions to neural integration are less clearly defined. Pharmacological inhibition or genetic ablation of kainate receptor activity reduces pain behaviors in a number of animal models of chronic pain, and small clinical trials have been conducted using several orthosteric antagonists. This review will cover kainate receptor function and participation in pain signaling as well as the pharmacological studies supporting further consideration as potential targets for therapeutic development.

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Topiramate in the treatment of migraine: A kainate (glutamate) receptor antagonist within the trigeminothalamic pathway

Cited by 78 publications

References 71 publications

Increased susceptibility to cortical spreading depression in an animal model of medication-overuse headache

Increased susceptibility to cortical spreading depression in an animal model of medication-overuse headache

Cervicogenic Headache

Kainate Receptor Signaling in Pain Pathways

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