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

Green, A Laine; Gu, Pengfei; Felice, Milena De; Dodick, David W.; Ossipov, Michael H.; Porreca, Frank

doi:10.1177/0333102413515344

Cited by 69 publications

(73 citation statements)

References 72 publications

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“…Medication-overuse headache is a major clinical problem (33), and has been observed with frequent use of SUMA (34). Administration of SUMA by minipump over multiple days has been shown previously to model medication-overuse headache (35,36). In this case chronic SUMA produced hyperalgesia in the head and peripheral regions concomitant with increased CGRP expression in trigeminal ganglia (35), and increased susceptibility to CSD (36).…”

Section: Discussionmentioning

confidence: 99%

The effects of acute and preventive migraine therapies in a mouse model of chronic migraine

Tipton

Tarash²,

McGuire³

et al. 2016

Cephalalgia

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Background The development of novel migraine therapies has been slow, in part because of the small number of clinically relevant animal models. We have recently developed a new mouse model of chronic migraine using chronic intermittent nitroglycerin, a known human migraine trigger. The objective of this study was to validate this model by testing known and potential migraine-preventive treatments. Methods Migraine therapies were administered to male and female mice for 11 days. On day 3, mice were tested with nitroglycerin every second day for nine days. Basal and nitroglycerin-evoked mechanical hypersensitivity was evaluated using von Frey filaments. Results Chronic intermittent nitroglycerin produced acute hyperalgesia with each administration, and progressive and sustained basal hypersensitivity. The established preventive migraine therapy propranolol effectively blocked the development of acute and chronic nitroglycerin-induced hyperalgesia, while valproate had no effect. Potential migraine-preventive therapies were also tested: Amiloride inhibited nitroglycerin-induced acute and chronic hyperalgesia; while memantine was ineffective. We also tested the acute migraine therapy sumatriptan, which did not alter nitroglycerin-induced hyperalgesia, but instead resulted in acute and chronic hyperalgesia similar to that observed following nitroglycerin administration. Conclusions This study establishes the chronic nitroglycerin model as an additional screening tool to test novel migraine-preventive therapies.

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Section: Discussionmentioning

confidence: 99%

The effects of acute and preventive migraine therapies in a mouse model of chronic migraine

Tipton

Tarash²,

McGuire³

et al. 2016

Cephalalgia

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“…Exposure to BLS was performed on days 20 and 21 post-sumatriptan treatment (46). Following the second BLS episode, periorbital and hindpaw withdrawal thresholds were tested at 1 h intervals over a 5 h time course.…”

Section: Methodsmentioning

confidence: 99%

Kappa opioid receptor antagonists: A possible new class of therapeutics for migraine prevention

et al. 2017

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Background: Stress is the most commonly reported migraine trigger. Dynorphin, an endogenous opioid peptide acting preferentially at kappa opioid receptors (KORs), is a key mediator of stress responses. The aim of this study was to use an injury-free rat model of functional cephalic pain with features of migraine and medication overuse headache (MOH) to test the possible preventive benefit of KOR blockade on stress-induced cephalic pain. Methods: Following sumatriptan priming to model MOH, rats were hyper-responsive to environmental stress, demonstrating delayed cephalic and extracephalic allodynia and increased levels of CGRP in the jugular blood, consistent with commonly observed clinical outcomes during migraine. Nor-binaltorphimine (nor-BNI), a long-acting KOR antagonist or CYM51317, a novel short-acting KOR antagonist, were given systemically either during sumatriptan priming or immediately before environmental stress challenge. The effects of KOR blockade in the amygdala on stress-induced allodynia was determined by administration of nor-BNI into the right or left central nucleus of the amygdala (CeA). Results: KOR blockade prevented both stress-induced allodynia and increased plasma CGRP. Stress increased dynorphin content and phosphorylated KOR in both the left and right CeA in sumatriptan-primed rats. However, KOR blockade only in the right CeA prevented stress-induced cephalic allodynia as well as extracephalic allodynia, measured in either the right or left hindpaws. U69,593, a KOR agonist, given into the right, but not the left, CeA, produced allodynia selectively in sumatriptan-primed rats. Both stress and U69,593-induced allodynia were prevented by right CeA U0126, a mitogen-activated protein kinase inhibitor, presumably acting downstream of KOR. Conclusions: Our data reveal a novel lateralized KOR circuit that mediated stress-induced cutaneous allodynia and increased plasma CGRP in an injury-free model of functional cephalic pain with features of migraine and medication overuse headache. Selective, small molecule, orally available, and reversible KOR antagonists are currently in development and may represent a novel class of preventive therapeutics for migraine.

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“…One limitation in their clinical use is that they can contribute to migraine chronification and more frequent episodes of headache, a condition referred to as medication overuse headache (MOH), recently characterized as a global epidemic [9; 11; 27; 28; 38; 41; 45; 77]. The triptan receptors are both Gi-protein coupled, which they share with other classes of analgesics, including those that act at mu-opioid or CB cannabinoid receptors [67; 74].…”

Section: Discussionmentioning

confidence: 99%

“…Also, the frequent use of triptans can lead to transition to MOH or chronic migraine [9; 10; 27; 28; 38; 41; 68; 77; 85]. We observed that sumatriptan produces a neuroplastic change in nociceptor function such that PGE 2 -induced mechanical hyperalgesia is markedly prolonged, a characteristic feature of both type I [4; 29; 33; 50; 57; 69; 73] and type II [7; 8] hyperalgesic priming.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, opioids, which are used clinically to treat moderate-to-severe pain, especially agonists at the mu-opioid receptor (MOR), may come to exacerbate or actually produce pain during their chronic administration, a phenomenon referred to as opioid-induced hyperalgesia (OIH) [6; 60; 63]. Similarly, the triptan class of drugs, used to treat migraine [25; 35; 76], also facilitates pain chronification and/or contributes to migraine chronification, a condition referred to as medication overuse headache (MOH; [9; 11; 26; 28; 38; 41; 45; 77]). The target for the therapeutic effect of triptans is thought to be 5-HT 1B and 5-HT 1D receptors that, like MOR are inhibitory G-protein coupled receptors (Gi-GPCRs) [37; 42; 64; 86; 95; 96].…”

Section: Introductionmentioning

confidence: 99%

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Gi-protein–coupled 5-HT1B/D receptor agonist sumatriptan induces type I hyperalgesic priming

Araldi

Ferrari

Levine

2016

Pain

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We have recently described a novel form of hyperalgesic priming (type II) induced by agonists at two clinically important Gi-protein coupled receptors (Gi-GPCRs), mu-opioid and A1-adenosine. Like mu-opioids, the anti-migraine triptans, which act at 5-HT1B/D Gi-GPCRs have been implicated in pain chronification. We determined if sumatriptan, a prototypical 5-HT1B/D agonist produces type II priming. Characteristic of hyperalgesic priming, intradermal injection of sumatriptan (10 ng) induced a change in nociceptor function such that a subsequent injection of prostaglandin-E2 (PGE2) induces prolonged mechanical hyperalgesia. However, onset to priming was delayed 3 days, characteristic of type I priming. Also characteristic of type I priming, a protein kinase Cε (PKCε), but not a PKA inhibitor attenuated the prolongation phase of PGE2 hyperalgesia. The prolongation of PGE2 hyperalgesia was also permanently reversed by intradermal injection of cordycepin, a protein translation inhibitor. Also, hyperalgesic priming did not occur in animals pre-treated with pertussis toxin or IB4-positive nociceptor toxin, IB4-saporin. Finally, as observed for other agonists that induce type I priming, sumatriptan did not induce priming in female rats. The prolongation of PGE2 hyperalgesia induced by sumatriptan was partially prevented by co-injection of antagonists for the 5-HT1B and 5-HT1D, but not 5-HT7, serotonin receptors, and completely prevented by co-administration of a combination of the 5-HT1B and 5-HT1D antagonists. Moreover, the injection of selective agonists, for 5-HT1B and 5-HT1D receptors, also induced hyperalgesic priming. Our results suggest that sumatriptan, which signals via Gi-GPCRs, induces type I hyperalgesic priming, unlike agonists at other Gi-GPCRs, which induce type II priming.

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

Cited by 69 publications

References 72 publications

The effects of acute and preventive migraine therapies in a mouse model of chronic migraine

The effects of acute and preventive migraine therapies in a mouse model of chronic migraine

Kappa opioid receptor antagonists: A possible new class of therapeutics for migraine prevention

Gi-protein–coupled 5-HT1B/D receptor agonist sumatriptan induces type I hyperalgesic priming

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