Rheumatoid Endothelinitis: A Novel Endothelin-1 Driven Neurovascular Phenotype Mimicking Refractory Chronic Migraine Article Swipe
Background: Chronic migraine is a heterogeneous disorder, yet current therapeutic protocols often apply a "one-size-fits-all" approach. A subset of patients remains refractory to standard preventative medications, including CGRP monoclonal antibodies and onabotulinumtoxinA (Botox). Hypothesis: We propose a novel disease model, Rheumatoid Endothelinitis, characterizing a phenotype suffering from systemic Endothelin-1 (ET-1) mediated microvascular dysregulation. Unlike classical migraine, this phenotype is driven by non-vesicular purinergic (ATP) signaling secondary to tissue ischemia. Methods: Through mathematical modeling of sensitization gain (G) versus ischemic input (I), and analysis of a longitudinal familial cohort, we delineate the physiological divergence between this condition and classical ME/CFS. We analyze pharmacological response patterns to identify diagnostic markers. Results: The phenotype is characterized by a specific "pharmacological fingerprint": intolerance to vasoconstrictors (triptans) and perfusion-reducing agents (beta-blockers), and non-response to vesicular release inhibitors (Botox). Conversely, interventions promoting hemodynamic shear stress (exercise), nitric oxide synthesis (e.g., Nebivolol), and neuroplastic regulation (e.g., Psilocybin) demonstrate efficacy or mechanistic rationale. Conclusion: We identify a specific endophenotype where pain is ischemic-metabolic rather than primarily neurogenic. This mandates a stratified therapeutic approach targeting the ET-1/glial axis, moving beyond standard neuromodulation to vascular restoration.
Related Topics
Concepts
Medicine
Phenotype
Neuroscience
Migraine
Disease
Neuromodulation
Endophenotype
Bioinformatics
Neurology
Immunology
Clinical phenotype
Blockade
Monoclonal antibody
Pathology
Rheumatoid arthritis
Multiple sclerosis
Clinical trial
Pain medicine
HDAC6
Sensitization
Refractory (planetary science)
Therapeutic approach
Chronic Migraine
Biomarker
Metadata
- Type
- article
- Landing Page
- https://doi.org/10.5281/zenodo.17808572
- OA Status
- green
- OpenAlex ID
- https://openalex.org/W7108685992
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W7108685992Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.5281/zenodo.17808572Digital Object Identifier
- Title
-
Rheumatoid Endothelinitis: A Novel Endothelin-1 Driven Neurovascular Phenotype Mimicking Refractory Chronic MigraineWork title
- Type
-
articleOpenAlex work type
- Publication year
-
2025Year of publication
- Publication date
-
2025-12-04Full publication date if available
- Authors
-
Ulltveit-Moe, NilsList of authors in order
- Landing page
-
https://doi.org/10.5281/zenodo.17808572Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.5281/zenodo.17808572Direct OA link when available
- Concepts
-
Medicine, Phenotype, Neuroscience, Migraine, Disease, Neuromodulation, Endophenotype, Bioinformatics, Neurology, Immunology, Clinical phenotype, Blockade, Monoclonal antibody, Pathology, Rheumatoid arthritis, Multiple sclerosis, Clinical trial, Pain medicine, HDAC6, Sensitization, Refractory (planetary science), Therapeutic approach, Chronic Migraine, BiomarkerTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
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| abstract_inverted_index.neuroplastic | 146 |
| abstract_inverted_index.non-response | 127 |
| abstract_inverted_index.preventative | 24 |
| abstract_inverted_index.restoration. | 185 |
| abstract_inverted_index.characterized | 112 |
| abstract_inverted_index.endophenotype | 160 |
| abstract_inverted_index.fingerprint": | 117 |
| abstract_inverted_index.heterogeneous | 5 |
| abstract_inverted_index.interventions | 134 |
| abstract_inverted_index.microvascular | 51 |
| abstract_inverted_index.non-vesicular | 61 |
| abstract_inverted_index.physiological | 91 |
| abstract_inverted_index.sensitization | 74 |
| abstract_inverted_index.characterizing | 42 |
| abstract_inverted_index.dysregulation. | 52 |
| abstract_inverted_index.Endothelinitis, | 41 |
| abstract_inverted_index.neuromodulation | 182 |
| abstract_inverted_index.pharmacological | 101 |
| abstract_inverted_index."pharmacological | 116 |
| abstract_inverted_index.(beta-blockers), | 125 |
| abstract_inverted_index.vasoconstrictors | 120 |
| abstract_inverted_index.ischemic-metabolic | 164 |
| abstract_inverted_index.onabotulinumtoxinA | 31 |
| abstract_inverted_index.perfusion-reducing | 123 |
| abstract_inverted_index."one-size-fits-all" | 14 |
| cited_by_percentile_year | |
| countries_distinct_count | 0 |
| institutions_distinct_count | 1 |
| citation_normalized_percentile.value | 0.78948744 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |