The Therapeutic Impact of New Migraine Discoveries

Vécsei, László; Lukács, Miklós; Tajti, János; Fülöp, Ferenc; Toldi, József; Edvinsson, Lars

doi:10.2174/0929867325666180530114534

Cited by 11 publications

(6 citation statements)

References 184 publications

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“…Furthermore, although the substances that cause migraine are normally vasodilators and both PACAP and VIP are vasoactive peptides, dilation of arterial vessels is not the only factor behind migraine [61]. In order to trigger the migraine attack, activation of the trigeminovascular system is believed to be essential [62,63]. Endogenous PACAP was proposed just as the mediator of this action, whose mechanisms, however, have not yet been clarified [59].…”

Section: Expert Opinionmentioning

confidence: 99%

Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review

Rustichelli

Castro

Baraldi

et al. 2020

Expert Opinion on Investigational Drugs

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Introduction: Interest is growing in the role of pituitary adenylate cyclase-activating polypeptide (PACAP) and its specific PAC1 receptor in migraine and in their antagonism as a strategy for migraine prevention. Areas covered: We discuss and critically evaluate (i) the evidence of the role of PACAP in migraine pathophysiology and (ii) the first clinical trials in migraine prophylaxis with monoclonal antibodies AMG 301 and ALD1910 which act against PAC1 and PACAP38 respectively. We examined PubMed, Scopus, and ClinicalTrials.gov electronic databases to examine the relevant material. Expert opinion: There is much proof of the ability of PACAP to cause migraine, but there is limited evidence that blocking PACAP or PAC1 receptor can prevent migraine. However, the potential of anti-PACAP antibodies in migraine prophylaxis is high. Theoretically, if these antibodies block the activation of the trigeminovascular system, they will prevent the onset of migraine attacks. There are still knowledge gaps in the role of PACAP in migraine and the risk/benefit ratio of anti-PACAP antibodies must be carefully studied.

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Section: Expert Opinionmentioning

confidence: 99%

Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review

Rustichelli

Castro

Baraldi

et al. 2020

Expert Opinion on Investigational Drugs

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“…Moreover, NSAIDs have been proved to be an effective treatment of antinociceptive e cacy to reduce the frequency of attacks and headache severity levels [10]. Besides the well-established role of the trigeminovascular system in migraine pathogenesis, the involvement of other brain phenomena such as cortical spreading depression (CSD) or neurogenic in ammation has become more and more established [23]. It has been hypothesized that the trigeminal sensory afferents were activated by the CSD mechanism, causing migraine attacks [24].…”

Section: Discussionmentioning

confidence: 99%

Potential Characteristics for Prediction of the Efficacy of Non-Steroid Anti-Inflammatory Drugs for Migraine Treatment: A Retrospective Cohort Study

Wei

Wang

Zhou

et al. 2021

Preprint

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Background: Although several special medications for migraine are currently available, non-steroid anti-inflammatory drugs (NSAIDs) are still the first-line pharmacological option. A considerable proportion of migraineurs still be unresponsive to NSAIDs for reasons that remain unknown. The study aimed to develop significant characteristics to predict the efficacy of NSAIDs for patients with migraine. Methods: In this retrospective study, 567 patients suffering migraine were included and divided into an effective NSAIDs (M-eNSAIDs) group and a noneffective NSAIDs (M-neNSAIDs) group according to the analgesic efficacy at 2 hours after taking NSAIDs. Clinical and neuropsychiatric characteristics were collected and used to build a logistic regression model. And a receiver operating characteristic (ROC) curve was drawn to represent the prediction capability.Results: Five predictors including education, attack duration, headache impact intensity, anxiety and depression scores were identified to build the logistic regression modal. The area under the curve (AUC) values of each predictor were 0.706, 0.639, 0.560, 0.683 and 0.632, respectively, failing to predict the efficacy of NSAIDs. All five predictors-combined method achieved an acceptable AUC value of 0.834 and a sensitivity of 90.9%.Conclusions: Despite the insufficient predictive capability of these predictors when analyzed individually, this study developed an effective and convenient method to accurately predict the efficacy of NSAIDs, which would be helpful for developing individualized therapeutic strategies for treatment of migraine.

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“…In experimental animals, TRPV1 antagonists blocked inflammatory, neuropathic, and cancer pain (Szallasi et al, 2007;Moran et al, 2011;Moran and Szallasi, 2018). However, in patients with migraine and osteoarthritis, TRPV1 inhibition disappointed as therapeutic approach (Mayorga et al, 2017;Arsenault et al, 2018;Vécsei et al, 2019). Likewise, TRPV1 antagonists inhibited evoked cough in experimental animals, but did not show any antitussive activity in chronic cough patients (Khalid et al, 2014;Belvisi et al, 2017).…”

Section: Concluding Thoughts: the Mysteries Of Capsaicin-sensitive Afmentioning

confidence: 99%

The Mysteries of Capsaicin-Sensitive Afferents

2020

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A fundamental subdivision of nociceptive sensory neurons is named after their unique sensitivity to capsaicin, the pungent ingredient in hot chili peppers: these are the capsaicin-sensitive afferents. The initial excitation by capsaicin of these neurons manifested as burning pain sensation is followed by a lasting refractory state, traditionally referred to as “capsaicin desensitization,” during which the previously excited neurons are unresponsive not only to capsaicin but a variety of unrelated stimuli including noxious heat. The long sought-after capsaicin receptor, now known as TRPV1 (transient receptor potential cation channel, subfamily V member 1), was cloned more than two decades ago. The substantial reduction of the inflammatory phenotype of Trpv1 knockout mice has spurred extensive efforts in the pharmaceutical industry to develop small molecule TRPV1 antagonists. However, adverse effects, most importantly hyperthermia and burn injuries, have so far prevented any compounds from progressing beyond Phase 2. There is increasing evidence that these limitations can be at least partially overcome by approaches outside of the mainstream pharmaceutical development, providing novel therapeutic options through TRPV1. Although ablation of the whole TRPV1-expressing nerve population by high dose capsaicin, or more selectively by intersectional genetics, has allowed researchers to investigate the functions of capsaicin-sensitive afferents in health and disease, several “mysteries” remain unsolved to date, including the molecular underpinnings of “capsaicin desensitization,” and the exact role these nerves play in thermoregulation and heat sensation. This review tries to shed some light on these capsaicin mechanisms.

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The Therapeutic Impact of New Migraine Discoveries

Cited by 11 publications

References 184 publications

Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review

Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) with monoclonal antibodies in migraine prevention: a brief review

Potential Characteristics for Prediction of the Efficacy of Non-Steroid Anti-Inflammatory Drugs for Migraine Treatment: A Retrospective Cohort Study

The Mysteries of Capsaicin-Sensitive Afferents

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