ReviewThe journal of headache and pain2026
Pharmacological mechanisms underlying neurovascular alterations related to resistant and refractory migraine: CGRP pathways and beyond.
Review in The journal of headache and pain, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- Common Mechanisms in Migraine, Migraine-Related Neck Pain, and Low Back Pain: Implications for Treatment.Pain and therapy · 2026Review
- Atogepant reduces triptan use: a pharmacoeconomic analysis in migraine prevention.The journal of headache and pain · 2026Observational
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMigraine is the fourth leading cause of disability worldwide. It impairs patients' physical, emotional and social functioning, as well as their productivity. This is also due to poor pharmacological control of attacks in difficult-to-treat patients. Despite several therapeutic strategies available, including the game-changing calcitonin gene-related peptide (CGRP)-targeted small-molecule and biotechnological drugs, 40% of patients remain resistant or even refractory. The aim of this review is to highlight the neurovascular mechanisms underlying poor response or nonresponse to antimigraine drugs, with particular focus on the phenomena related to the CGRP pathway.
methodsEligibility criteria, search strategy and information sources were established a priori: PubMed, Scopus, Cochrane Library, Web of Science and ScienceDirect were searched for studies published from database inception to the date of the last search on July 05th, 2025.
resultsNon-response to antimigraine treatment is closely linked to clinical and neurobiological factors that increase the overall disease burden. Underlying these challenges are mechanisms involving genetic and epigenetic modifications that contribute to inter-individual variability in pharmacokinetics and pharmacodynamics. Additionally, CGRP as well as other neuropeptides, implicated in the neurovascular basis of migraine, may play a significant role. Targeting these mechanisms may help overcome treatment resistance and refractoriness, as defined by the European Headache Federation. Combination therapies, including the latest available treatments, might represent a promising strategy. Thus, they deserve further investigation to confirm efficacy without worsening the safety profile.
conclusionsA deeper understanding of the neurovascular pharmacology and pathophysiology of migraine is essential to pave the way for more personalized and effective treatments. tudies are needed to clarify the neuropharmacological, genetic, and epigenetic mechanisms that underlie resistance and refractoriness to pharmacological therapies, affecting the CGRP pathway both directly and indirectly. CLINICAL TRIAL NUMBER: Not applicable.
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