ArticleCephalalgia : an international journal of headache2021
Combined onabotulinumtoxinA/atogepant treatment blocks activation/sensitization of high-threshold and wide-dynamic range neurons.
Article in Cephalalgia : an international journal of headache, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- CGRP and Migraine: Real-World Insights and Future Therapeutic Directions.Annual review of medicine · 2026Review
- Is canonical SD a clinically relevant model of migraine? Argument pro.The journal of headache and pain · 2025Review
- Spreading depolarization as a therapeutic target in migraine.Nature reviews. Neurology · 2025Review
- Oral atogepant mitigates spreading depolarization-induced pain and anxiety behavior in mice.The journal of headache and pain · 2025Article
- Small-molecule CGRP antagonist atogepant does not affect cortical spreading depression susceptibility in rats.The journal of headache and pain · 2025Article
- Gepants: Key Features of A Potent Therapeutic Option and Considerations in The Latin American Context.Revista de neurologia · 2025Review
- The mysterious link between migraine aura and migraine headache.PLoS biology · 2025Article
- Real-World Evidence of the Safety and Effectiveness of Atogepant Added to OnabotulinumtoxinA for the Preventive Treatment of Chronic Migraine: A Retrospective Chart Review.Pain and therapy · 2024Article
- Insights from 25 years of onabotulinumtoxinA in migraine - mechanisms and management.Nature reviews. Neurology · 2024Review
- Novel insight into atogepant mechanisms of action in migraine prevention.Brain : a journal of neurology · 2024Article
- New perspectives on migraine treatment: a review of the mechanisms and effects of complementary and alternative therapies.Frontiers in neurology · 2024Review
- Update of Gepants in the Treatment of Chronic Migraine.Current pain and headache reports · 2023Review
- Multimodal Migraine Management and the Pursuit of Migraine Freedom: A Narrative Review.Neurology and therapy · 2023Review
- Real-world effectiveness, satisfaction, and optimization of ubrogepant for the acute treatment of migraine in combination with onabotulinumtoxinA: results from the COURAGE Study.The journal of headache and pain · 2023Observational
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- Breaking the cycle: unraveling the diagnostic, pathophysiological and treatment challenges of refractory migraine.Frontiers in neurology · 2023Review
- Gepants for Acute and Preventive Migraine Treatment: A Narrative Review.Brain sciences · 2022Review
- Atogepant - an orally-administered CGRP antagonist - attenuates activation of meningeal nociceptors by CSD.Cephalalgia : an international journal of headache · 2022Article
- New Generation Gepants: Migraine Acute and Preventive Medications.Journal of clinical medicine · 2022Review
- [CGRP antibodies in migraine prophylaxis : The new standard in migraine treatment?]Schmerz (Berlin, Germany) · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOnabotulinumtoxinA and agents that block calcitonin gene‒receptor peptide action have both been found to have anti-migraine effects, but they inhibit different populations of meningeal nociceptors. We therefore tested the effects of combined treatment with onabotulinumtoxinA and the calcitonin gene‒receptor peptide antagonist atogepant on activation/sensitization of trigeminovascular neurons by cortical spreading depression. MATERIAL AND
methodsSingle-unit recordings were obtained of high-threshold and wide-dynamic-range neurons in the spinal trigeminal nucleus, and cortical spreading depression was then induced in anesthetized rats that had received scalp injections of onabotulinumtoxinA 7 days earlier and intravenous atogepant infusion 1 h earlier. The control group received scalp saline injections and intravenous vehicle infusion.
resultsOnabotulinumtoxinA/atogepant pretreatment prevented cortical spreading depression-induced activation and sensitization in both populations (control: Activation in 80% of high-threshold and 70% of wide-dynamic-range neurons, sensitization in 80% of high-threshold and 60% of wide-dynamic-range neurons; treatment: activation in 10% of high-threshold and 0% of wide-dynamic-range neurons, sensitization in 0% of high-threshold and 5% of wide-dynamic-range neurons). DISCUSSION: We propose that the robust inhibition of high-threshold and wide-dynamic-range neurons by the combination treatment was achieved through dual blockade of the Aδ and C classes of meningeal nociceptors. Combination therapy that inhibits meningeal C-fibers and prevents calcitonin gene‒receptor peptide from activating its receptors on Aδ-meningeal nociceptors may be more effective than a monotherapy in reducing migraine days per month in patients with chronic migraine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.