Dodick, David

Background There is a considerable amount of practice variation in managing migraines in emergency settings, and evidence-based therapies are often not used first line. Methods A peer-reviewed search of databases (MEDLINE, Embase, CENTRAL) was carried out to identify randomized and quasi-randomized controlled trials of interventions for acute pain relief in adults presenting with migraine to emergency settings. Where possible, data were pooled into meta-analyses. Results Two independent reviewers screened 831 titles and abstracts for eligibility. Three independent reviewers subsequently evaluated 120 full text articles for inclusion, of which 44 were included. Individual studies were then assigned a US Preventive Services Task Force quality rating. The GRADE scheme was used to assign a level of evidence and recommendation strength for each intervention. Interpretation We strongly recommend the use of prochlorperazine based on a high level of evidence, lysine acetylsalicylic acid, metoclopramide and sumatriptan, based on a moderate level of evidence, and ketorolac, based on a low level of evidence. We weakly recommend the use of chlorpromazine based on a moderate level of evidence, and ergotamine, dihydroergotamine, lidocaine intranasal and meperidine, based on a low level of evidence. We found evidence to recommend strongly against the use of dexamethasone, based on a moderate level of evidence, and granisetron, haloperidol and trimethobenzamide based on a low level of evidence. Based on moderate-quality evidence, we recommend weakly against the use of acetaminophen and magnesium sulfate. Based on low-quality evidence, we recommend weakly against the use of diclofenac, droperidol, lidocaine intravenous, lysine clonixinate, morphine, propofol, sodium valproate and tramadol.

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.