Neurobiology of migraine progression

Rattanawong, Wanakorn; Rapoport, Alan M.; Srikiatkhachorn, Anan

doi:10.1016/j.ynpai.2022.100094

Cited by 17 publications

(32 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As gepants and CGRP(-receptor) targeted mAbs become more widely available to EM and CM patients, more robust clinical trials will need to be conducted – not only looking at efficacy, but also discontinuation effects. Furthermore, more basic studies are needed to better understand the pathophysiological mechanisms that accompany stopping (oral) prophylactic drugs and the neurobiological processes that underlie migraine progression [ 140 ]. Ultimately, the identification of (several) objective biomarkers for disease improvement and prognostic (clinical) features of treatment relapse would bring advantages in determining whether and which migraine patients would benefit from discontinuing migraine prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

The sense of stopping migraine prophylaxis

et al. 2023

View full text Add to dashboard Cite

Introduction Migraine prophylactic therapy has changed over recent years with the development and approval of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway. As new therapies emerged, leading headache societies have been providing guidelines on the initiation and escalation of such therapies. However, there is a lack of robust evidence looking at the duration of successful prophylaxis and the effects of therapy discontinuation. In this narrative review we explore both the biological and clinical rationale for prophylactic therapy discontinuation to provide a basis for clinical decision-making. Methods Three different literature search strategies were conducted for this narrative review. These include i) stopping rules in comorbidities of migraine in which overlapping preventives are prescribed, notably depression and epilepsy; ii) stopping rules of oral treatment and botox; iii) stopping rules of antibodies targeting the CGRP (receptor). Keywords were utilized in the following databases: Embase, Medline ALL, Web of Science Core collection, Cochran Central Register of Controlled Trials, and Google Scholar. Discussion Reasons to guide decision-making in stopping prophylactic migraine therapies include adverse events, efficacy failure, drug holiday following long-term administration, and patient-specific reasons. Certain guidelines contain both positive and negative stopping rules. Following withdrawal of migraine prophylaxis, migraine burden may return to pre-treatment level, remain unchanged, or lie somewhere in-between. The current suggestion to discontinue CGRP(-receptor) targeted mAbs after 6 to 12 months is based on expert opinion, as opposed to robust scientific evidence. Current guidelines advise the clinician to assess the success of CGRP(-receptor) targeted mAbs after three months. Based on excellent tolerability data and the absence of scientific data, we propose if no other reasons apply, to stop the use of mAbs when the number of migraine days decreases to four or fewer migraine days per month. There is a higher likelihood of developing side effects with oral migraine preventatives, and so we suggest stopping these drugs according to the national guidelines if they are well tolerated. Conclusion Translational and basic studies are warranted to investigate the long-term effects of a preventive drug after its discontinuation, starting from what is known about the biology of migraine. In addition, observational studies and, eventually, clinical trials focusing on the effect of discontinuation of migraine prophylactic therapies, are essential to substantiate evidence-based recommendations on stopping rules for both oral preventives and CGRP(-receptor) targeted therapies in migraine. Graphical Abstract

show abstract

Section: Discussionmentioning

confidence: 99%

The sense of stopping migraine prophylaxis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…In each of the phases of migraine (premonitory, aura, headache, and postdrome), specific physiological mechanisms in specific brain regions occur. Symptoms in the premonitory phase of migraine suggest hypothalamic and brainstem dysfunction, and symptoms in the aura phase represent focal cortical dysfunction 2 . In the headache phase, activation of the trigeminovascular system and release of predominately CGRP has been identified as the primary mechanism where increased sensitivity of trigeminal nociceptors that innervate the dura mater is responsible for intracranial headache pain.…”

Section: Introductionmentioning

confidence: 99%

“…Migraine is classified as episodic migraine (EM; <15 headache days per month) or chronic migraine (CM; ≥15 headache days per month for more than 3 months, with features of migraine ≥8 days per month) based on attack frequency. Proper management of migraine with acute and/or preventive treatment may impede migraine chronification, where the most significant measure of progression to CM is the increase in headache frequency 2 . Medication overuse headache (MOH) has also been identified as a strong risk factor for the progression of migraine 3 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Atogepant: Mechanism of action, clinical and translational science

Boinpally,

Shebley,

Trugman

2024

Clinical Translational Sci

View full text Add to dashboard Cite

Since the discovery of calcitonin gene‐related peptide (CGRP) in 1982, its integral role in migraine pathophysiology, specifically migraine pain, has been demonstrated through cumulative scientific discoveries that have led to the development and approval of migraine‐specific therapeutics. Today, eight drugs, including monoclonal antibodies and small molecule CGRP receptor antagonists, known as gepants, have received approval for acute or preventive treatment of migraine. The primary mechanism of these drugs is to block CGRP signaling, thus preventing CGRP‐mediated nociception and neurogenic inflammation. Here, we focus on atogepant, a highly potent and selective gepant and the first and only oral medication approved for the preventive treatment of both episodic and chronic migraine in adults. In this article, we summarize the role of CGRP in migraine pathophysiology and the mechanism of action of atogepant. In addition, we provide an overview of atogepant's pharmacology and the key clinical trials and outcomes that have demonstrated the safety and efficacy of atogepant.

show abstract

“…To generate nociceptive signalling, which is further transmitted to the spinal cord/brainstem and to the higher pain centers, the trigeminal nerve terminals in the meninges should be first depolarized to a threshold sufficient to generate spiking activity [7]. To date, a lot of depolarizing stimuli were proposed to trigger such a depolarization [8] including extracellular ATP, serotonin, endovanilloids, low extracellular pH, mechanical forces and/or changes in the ambient temperature [7,9,10]. In addition to produce nociceptive firing, depolarization of meningeal peptidergic C-fibers can release calcitonin gene-related peptide (CGRP), which nowadays is considered a principal contributor to migraine attacks and an important target for migraine treatment [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Role of ATP in migraine mechanisms: focus on P2X3 receptors

Giniatullin

Nistri

2023

J Headache Pain

View full text Add to dashboard Cite

Migraine is a major health burden worldwide with complex pathophysiology and multifarious underlying mechanisms. One poorly understood issue concerns the early steps in the generation of migraine pain. To elucidate the basic process of migraine pain further, it seems useful to consider key molecular players that may operate synergistically to evoke headache. While the neuropeptide CGRP is an important contributor, we propose that extracellular ATP (that generally plays a powerful nociceptive role) is also a major component of migraine headache, acting in concert with CGRP to stimulate trigeminal nociceptive neurons. The aim of the present focused review is to highlight the role of ATP activating its P2X3 membrane receptors selectively expressed by sensory neurons including their nerve fiber terminals in the meninges. Specifically, we present data on the homeostasis of ATP and related purines in the trigeminovascular system and in the CNS; the basic properties of ATP signalling at peripheral and central nerve terminals; the characteristics of P2X3 and related receptors in trigeminal neurons; the critical speed and persistence of P2X3 receptor activity; their cohabitation at the so-called meningeal neuro-immune synapse; the identity of certain endogenous agents cooperating with ATP to induce neuronal sensitization in the trigeminal sensory system; the role of P2X3 receptors in familial type migraine; the current state of P2X3 receptor antagonists and their pharmacological perspectives in migraine. It is proposed that the unique kinetic properties of P2X3 receptors activated by ATP offer an interesting translational value to stimulate future studies for innovative treatments of migraine pain.

show abstract

Neurobiology of migraine progression

Cited by 17 publications

References 124 publications

The sense of stopping migraine prophylaxis

The sense of stopping migraine prophylaxis

Atogepant: Mechanism of action, clinical and translational science

Role of ATP in migraine mechanisms: focus on P2X3 receptors

Contact Info

Product

Resources

About