Migraine: An Overview

Salomone, Salvatore; Caraci, Filippo; Capasso, Anna

doi:10.2174/1874205x00903010064

Cited by 15 publications

(9 citation statements)

References 64 publications

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“…Current research suggests that inflammation in the blood vessels of the brain causes them to swell and press on nearby nerves, causing pain (Salomone et al, 2009). This inflammation may arise in or be stimulated by signals from the trigeminal nerve, the main sensory nerve of the face (Debruyne and Herroelen, 2009).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of combined topiramate/thioctic acid therapy in migraine prophylaxis

Ali

Awad

Al-Adl

2010

Saudi Pharmaceutical Journal

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Migraine cannot be cured and the aim, shared with the patient, is to minimise the impact of the illness on the patient's life and lifestyle. The aim of prophylaxis is to reduce the number of migraine attacks. Prophylaxis should be considered when appropriately used acute management gives inadequate control of symptoms. The efficacy and safety of topiramate 50 mg/d and thioctic acid (α-lipoic acid) 300 mg/d either as monotherapy or in combination were investigated as migraine prophylactic agents. Forty secondary school migraineur girls were enrolled in the study. The study was conducted in two phases, a prospective baseline phase and 1-month treatment phase. Combined topiramate/thioctic acid therapy was more effective than either topiramate or thioctic acid monotherapy as a migraine-preventive treatment. Combined topiramate/thioctic acid therapy decreased the mean monthly migraine frequency from 5.86 ± 1.2 to 2.6 ± 0.98 (p ⩽ 0.05), topiramate (50 mg/d) from 5.71 ± 1.4 to 4.75 ± 1.5 and thioctic acid (300 mg/d) from 5.68 ± 1.6 to 5.22 ± 1.8. Reduction in mean monthly migraine days was also significantly greater in the group receiving combined topiramate/thioctic acid (from 12.32 ± 1.85 to 5.74 ± 1.1) compared to those receiving either topiramate 50 mg/d (from 12.7 ± 1.34 to 11.85 ± 1.35) or thioctic acid 300 mg/d (from 12.5 ± 1.72 to 11.65 ± 1.44). The responder rate (% of patients showing ⩾50% reduction in monthly migraine frequency) was 85% in patients receiving combined topiramate/thioctic acid therapy compared to 30% and 20% in patients receiving either topiramate or thioctic acid, respectively. The incidence of adverse events was higher in patients receiving topiramate (50 mg/d) monotherapy. The most common adverse events were nausea, fatigue, paraesthesia and taste perversion. We conclude that combined topiramate/thioctic acid therapy is more effective and better tolerated than topiramate monotherapy. The combination has lower monthly medication costs compared to the traditionally used topiramate 100 mg monotherapy.

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Section: Introductionmentioning

confidence: 99%

Efficacy of combined topiramate/thioctic acid therapy in migraine prophylaxis

Ali

Awad

Al-Adl

2010

Saudi Pharmaceutical Journal

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“…Current understanding suggests that migraine pain ultimately requires activation of nociceptors in the cranial meninges (2–4). This process likely involves dural immune mast cell (MC) degranulation, which leads to secretion of inflammatory mediators, cytokines, chemokines and proteases, all of which may promote activation of meningeal nociceptors (7–10). Tryptase, the most abundant MC protease, has been demonstrated to stimulate MC, as well as trigeminal nociceptors, by activating the protease activated receptor 2 (PAR2) (7–9).…”

Section: Introductionmentioning

confidence: 99%

Characterization and preclinical evaluation of a protease activated receptor 2 (PAR2) monoclonal antibody as a preventive therapy for migraine

et al. 2020

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Aim Migraine pain is thought to result from activation of meningeal nociceptors that might involve dural mast cell degranulation and release of proteases and pronociceptive mediators. Tryptase, the most abundant dural mast cell protease, has been demonstrated to stimulate dural mast cells, as well as trigeminal nociceptors by activating the protease activated receptor 2. Mast cell or neuronal protease activated receptors 2 may therefore represent a novel target for migraine treatment. In this study, we characterized and evaluated a novel protease activated receptor 2 monoclonal antibody as a preventive anti-migraine pain therapy in preclinical models. Methods Flow cytometry, immunocytochemistry, calcium imaging, Homogeneous Time Resolved Technology (HTRF) epitope competition assay and serum pharmacokinetic (PK) assay in rats were performed to confirm the activity, specificity and in vivo stability of PAR650097, a novel anti- protease activated receptor 2 monoclonal antibody. In vivo assessment was performed in female C57BL/6J mice by evaluation of PAR650097 in preventing cutaneous allodynia elicited by (a) supradural injection of the protease activated receptor 2 agonist, Ser-Leu-Ile-Gly-Arg-Leu-amide trifluoroacetate (SLIGRL), or calcitonin gene-related (CGRP) peptide, and (b) induction of latent sensitization by priming with three daily episodes of restraint stress followed by challenge with a subthreshold inhalational exposure to umbellulone (UMB), a transient receptor potential ankyrin 1 (TRPA1) agonist. PAR650097 was administered as a pretreatment prior to the first restraint stress, umbellulone exposure, SLIGRL or calcitonin gene-related peptide injection. Additionally, fremanezumab, a calcitonin gene-related peptide antibody was administered as pre-treatment prior to supradural administration of calcitonin gene-related peptide or SLIGRL. Results In vitro, PAR650097 demonstrated rapid interaction with protease activated receptor 2, enabling it to fully inhibit protease-induced protease activated receptor 2 activation, in human and mouse cells, with high potency. Furthermore, PAR650097 was highly selective for protease activated receptor 2, demonstrating no affinity for protease activated receptor 1 protein and no functional effect on the activation of cellular protease activated receptor 1 with thrombin. In addition, PAR650097 had an acceptable PK profile, compatible with testing the effects of selective protease activated receptor 2 inhibition in vivo. In vivo, PAR650097 blocked cutaneous allodynia induced by either supradural SLIGRL or calcitonin gene-related peptide. Fremanezumab abolished cutaneous allodynia induced by supradural CGRP, and partially attenuated cutaneous allodynia induced by SLIGRL. Administration of PAR650097, before the first restraint stress episode, did not prevent the acute stress-induced cutaneous allodynia or restraint stress priming revealed by cutaneous allodynia induced by inhalational umbellulone. In contrast, PAR650097 prevented expression of cutaneous allodynia when given before the umbellulone challenge in restraint stress-primed animals. Conclusion PAR650097 specifically inhibits endogenously expressed protease activated receptor 2 in human and mouse cells with high potency. This antibody has an acceptable PK profile in rodents and effectively blocked SLIGR-induced cutaneous allodynia. PAR650097 additionally prevented cutaneous allodynia induced by supradural calcitonin gene-related peptide, indicating that the protease activated receptor 2 receptor is a downstream consequence of calcitonin gene-related peptide actions. Fremanezumab effectively blocked calcitonin gene-related peptide-induced cutaneous allodynia and only partially reduced cutaneous allodynia induced by a protease activated receptor 2 activator, suggesting both calcitonin gene-related peptide-dependent and -independent mechanisms in promoting migraine pain. While PAR650097 did not prevent stress-induced cutaneous allodynia or priming, it effectively prevented cutaneous allodynia induced by a TRPA1 agonist in animals with latent sensitization. Activation of protease activated receptor 2, therefore, contributes to both calcitonin gene-related peptide-dependent and -independent mechanisms in promoting migraine-like pain. Therapeutic targeting of protease activated receptor 2 receptors may represent an anti-migraine pain strategy with a potentially broad efficacy profile.

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“…[2] Migren baş ağrısı fiziksel aktivite, baş hareketleri ile ağırlaşır, ataklar sıra-sında bulantı ve/veya kusma, fotofobi ve fonofobi görülür. [1] Değişik toplumlarda görülme sıklığı hafifçe değiş-mekle birlikte, her toplumda kadınlarda iki-üç kat daha sık görülmektedir.…”

Section: Introductionunclassified

“…Atakların sıklığı oldukça değişkendir; bazı hastalarda yaşam boyu birkaç kere olabiliyorken, bir diğer grup hasta haftada birkaç atak yaşayabilmekte, çoğu migren hastası ise bir ay içerisinde ortalama bir-üç atak yaşamaktadır. [2] Migren türü baş ağrısının bir diğer özelliği de taraf değiştirebilmesidir. Aynı kişide bile ağrı bazen başın tümünde bazen yarısında hissedilebilir veya aynı kişide bazen sağ, bazen de sol hemikranial olabilir.…”

Section: Introductionunclassified