The Effects of Flunarizine in Experimental Models Related to the Pathogenesis of Migraine

Wauquier, A.; Ashton, David; Marrannes, Roger

doi:10.1177/03331024850050s222

Cited by 41 publications

(26 citation statements)

References 5 publications

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“…Plenty of evidences have shown that CSD is a common therapeutic target for currently prescribed migraine prophylactic drugs [29]. Preventive effects for LH prophylaxis were observed after using drugs which had been shown able to suppress CSD [30,31], yet, no effect observed for the antiepileptic drugs carbamazepine and oxcarbazepine which had been shown effective in many types of neuropathic pain. Though the non-efficiency of carbamazepine and oxcarbazepine on LH was observed only in two patients, this is consistent with their lack of efficacy on migraine [24,29] as well as on CSD [32,33].…”

Section: Discussionmentioning

confidence: 99%

Linear headache: a recurrent unilateral head pain circumscribed in a line-shaped area

et al. 2014

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BackgroundA headache circumscribed in a line-shaped area but not confined to the territory of one particular nerve had ever been described in Epicrania Fugax (EF) of which the head pain is moving and ultrashort. In a 25-month period from Feb 2012 to Mar 2014, we encountered 12 patients with a paroxysmal motionless head pain restricted in a linear trajectory. The head pain trajectory was similar to that of EF, but its all other features obviously different from those of EF. We named this distinctive but undescribed type of headache linear headache (LH).MethodsA detailed clinical feature of the headache was obtained in all cases to differentiate with EF, trigeminal autonomic cephalalgias (TACs) and cranial neuralgia. Similarities and differences in clinical features were compared between LH and migraine.ResultsThe twelve LH patients (mean age 43.9 ± 12.2) complained of a recurrent, moderate to severe, distending (n = 9), pressure-like (n = 3) or pulsating (n = 3) pain within a strictly unilateral line-shaped area. The painful line is distributed from occipital or occipitocervical region to the ipsilateral eye (n = 5), forehead (n = 6) or parietal region (n = 1). The pain line has a trajecory similar to that of EF but no characteristics of moving. The headache duration would be ranged from five minutes to three days, but usually from half day to one day in most cases (n = 8). Six patients had the accompaniment of nausea with or without vomiting, and two patients had the accompaniment of ipsilateral dizziness. The attacks could be either spontaneous (n = 10) or triggered by noise, depression and resting after physical activity (n = 1), or by stress and staying up late (n = 1). The frequency of attacks was variable. The patients had well response to flunarizine, sodium valproate and amitriptyline but not to carbamazepine or oxcarbazepine. LH is different from EF, trigeminal autonomic cephalalgias (TACs) and cranial neuralgia, but it had couple of features similar to that of migraine.ConclusionsThe clinical picture of LH might be a subtype of migraine, or represent a novel syndrome.

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Section: Discussionmentioning

confidence: 99%

Linear headache: a recurrent unilateral head pain circumscribed in a line-shaped area

et al. 2014

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“…Nonspecific Ca 2ϩ channel antagonism previously has been shown to effect the initiation and propagation of SD in acute brain slices (Wauquier et al, 1985;Jing et al, 1993;Footitt and Newberry, 1998;Takagi et al, 1998) and in vivo (Marrannes et al, 1993). However, deciphering whether such changes are due to Ca 2ϩ channel function per se is made difficult by other nonspecific effects of the antagonists.…”

Section: P/q Ca 2؉ Channel Blockadementioning

confidence: 99%

“…Interstitial Ca 2ϩ falls by more than 90% during SD (Nicholson et al, 1977), with at least some of this loss thought to enter presynaptic terminals and thus markedly enhance Ca 2ϩ -dependent transmitter release . In fact, nonselective Ca 2ϩ channel antagonists can delay the initiation (Wauquier et al, 1985;Takagi et al, 1998) and block the propagation of SD (Jing et al, 1993). Also, generalized blockade of voltage-gated Ca 2ϩ channels can retard the induction of SD in rat neocortex (Richter et al, 2002).…”

Section: Camentioning

confidence: 99%

P/Q Ca²⁺ channel blockade stops spreading depression and related pyramidal neuronal Ca²⁺ rise in hippocampal organ culture

Kunkler

Kraig

2003

Hippocampus

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Ca2+ channels and pyramidal cell Ca2+ are involved in hippocampal spreading depression (SD), but their roles remain elusive. Accordingly, we characterized Ca2+ changes during SD in CA3 pyramidal neurons and determined whether Ca2+ channel antagonists could prevent SD. SD was induced in hippocampal organotypic cultures (HOTCs), in which experimental conditions can be rigorously controlled. SD was triggered by transient exposure to sodium acetate (NaAc)-based Ringer's coupled to an electrical pulse in the dentate gyrus and its occurrence confirmed with interstitial DC recordings. Pyramidal cell Ca2+ was measured with fura-2 filled cells and was quantified at the soma, proximal and more distal apical dendrites. Regional Ca2+ changes began simultaneously with the triggering pulse of SD and reached three distinct peaks before returning to baseline concomitant with the interstitial DC potential of SD. The first peak occurred within 5 s of the triggering pulse, was smallest, and heralded the onset of SD. The second Ca2+ change was the greatest and reached a peak 6 s later, during the early phase of SD. The third was intermediate in size and occurred 18 s later, as SD reached its maximum interstitial DC change. SD was prevented by nonselective Ca2+ blockade (Ni2+ and Cd2+) but not by either L-Ca2+ channel (nifedipine) or N-Ca2+ channel inhibition (omega-conotoxin GVIA). Importantly, SD was blocked by P/Q Ca2+ channel antagonism (omega-agatoxin-IVA), which also prompted a significant reduction in pyramidal cell Ca2+ change and hyperexcitability. These results show that the spatiotemporal pattern of pyramidal cell Ca2+ change with SD is multiphasic; they provide further evidence that these changes begin before electrophysiologic evidence of SD. Furthermore, they show that P/Q Ca2+ channel antagonism can prevent SD in HOTCs and it appears to do so by preventing the NaAc-induced increased pyramidal cell excitability from NaAc exposure, which may involve altered GABAergic transmission.

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“…Five clinically effective migraine prophylactic drugs (valproate, topiramate, propranolol, amitriptyline, methysergide) were shown to suppress SD susceptibility [38]. Flunarizine showed a somewhat dose-dependent CSD suppression [39]. …”

Section: Discussionmentioning

confidence: 99%

Protection of flunarizine on cerebral mitochondria injury induced by cortical spreading depression under hypoxic conditions

Qiu

Dong

et al. 2011

J Headache Pain

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A rat cortical spreading depression (CSD) model was established to explore whether cerebral mitochondria injury was induced by CSD under both normoxic and hypoxic conditions and whether flunarizine had a protective effect on cerebral mitochondria. SD rats, which were divided into seven groups, received treatment as follows: no intervention (control Group I); 1 M NaCl injections (Group II); 1 M KCl injections (Group III); intraperitoneal flunarizine (3 mg/kg) 30 min before KCl injections (Group IV); 14% O2 inhalation before NaCl injections (Group V); 14% O2 inhalation followed by KCl injections (Group VI); 14% O2 inhalation and intraperitoneal flunarizine followed by KCl injections (Group VII). Following treatment, brains were removed for the analysis of mitochondria transmembrane potential (MMP) and oxidative respiratory function after recording the number, amplitude and duration of CSD. The duration of CSD was significantly longer in Group VI than that in Group III. The number and duration of CSD in Group VII was significantly lower than that in Group VI. MMP in Group VI was significantly lower than that in Group III, and MMP in Group VII was significantly higher than that in Group VI. State 4 respiration in Group VI was significantly higher than that in Group III, and state 3 respiration in Group VII was significantly higher than that in Group VI. Respiration control of rate in Group VII was also significantly higher than that in Group VI. Thus, we concluded that aggravated cerebral mitochondria injury might be attributed to CSD under hypoxic conditions. Flunarizine can alleviate such cerebral mitochondria injury under both normoxic and hypoxic conditions.

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The Effects of Flunarizine in Experimental Models Related to the Pathogenesis of Migraine

Cited by 41 publications

References 5 publications

Linear headache: a recurrent unilateral head pain circumscribed in a line-shaped area

Linear headache: a recurrent unilateral head pain circumscribed in a line-shaped area

P/Q Ca²⁺ channel blockade stops spreading depression and related pyramidal neuronal Ca²⁺ rise in hippocampal organ culture

Protection of flunarizine on cerebral mitochondria injury induced by cortical spreading depression under hypoxic conditions

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The Effects of Flunarizine in Experimental Models Related to the Pathogenesis of Migraine

Cited by 41 publications

References 5 publications

Linear headache: a recurrent unilateral head pain circumscribed in a line-shaped area

Linear headache: a recurrent unilateral head pain circumscribed in a line-shaped area

P/Q Ca2+ channel blockade stops spreading depression and related pyramidal neuronal Ca2+ rise in hippocampal organ culture

Protection of flunarizine on cerebral mitochondria injury induced by cortical spreading depression under hypoxic conditions

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P/Q Ca²⁺ channel blockade stops spreading depression and related pyramidal neuronal Ca²⁺ rise in hippocampal organ culture