ArticlePain2013
Parthenolide inhibits nociception and neurogenic vasodilatation in the trigeminovascular system by targeting the TRPA1 channel.
Article in Pain, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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.
The trial behind it
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
60 citing papers in PubMed, 115 citations in OpenAlex.
- Sesquiterpene Lactone Derivatives ofPharmaceuticals (Basel, Switzerland) · 2026Article
- Chronic Pain and Cognitive Dysfunction: Clinical Implement, Mechanism, and Therapeutic Strategy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- NF-κB inhibition attenuates sympathetic hyperreflexia and concomitant development of autonomic dysreflexia and immune dysfunction after spinal cord injury.Communications biology · 2025Article
- Parthenolide ameliorates glucocorticoid-induced inhibition of osteogenic differentiation and osteoporosis by activating ERK signaling pathway.Journal of orthopaedic surgery and research · 2025Article
- Bridging Gaps in Migraine Management: A Comprehensive Review of Conventional Treatments, Natural Supplements, Complementary Therapies, and Lifestyle Modifications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Parthenolide: pioneering new frontiers in hematological malignancies.Frontiers in pharmacology · 2025Review
- Role of TRPA1 in the pharmacological effect triggered by the topical application of trans-anethole in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Review
- TRPA1-Related Diseases and Applications of Nanotherapy.International journal of molecular sciences · 2024Review
- Article
- Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases.Frontiers in pharmacology · 2024Review
- Advances in understanding migraine pathophysiology: a bench to bedside review of research insights and therapeutics.Frontiers in molecular neuroscience · 2024Review
- Modulation of TRPV1 and TRPA1 Channels Function by Sea Anemones' Peptides Enhances the Viability of SH-SY5Y Cell Model of Parkinson's Disease.International journal of molecular sciences · 2023Article
- Regioselective and Stereoselective Synthesis of Parthenolide Analogs by Acyl Nitroso-Ene Reaction and Their Biological Evaluation againstInternational journal of molecular sciences · 2023Article
- Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis.Marine drugs · 2023Article
- Xenobiotic Exposure and Migraine-Associated Signaling: A Multimethod Experimental Study Exploring Cellular Assays in Combination withEnvironmental health perspectives · 2023Article
- TRP Channels in Cancer: Signaling Mechanisms and Translational Approaches.Biomolecules · 2023Review
- Epigenetic Connections of the TRPA1 Ion Channel in Pain Transmission and Neurogenic Inflammation - a Therapeutic Perspective in Migraine?Molecular neurobiology · 2023Review
- Future targets for migraine treatment beyond CGRP.The journal of headache and pain · 2023Review
- Targeting Nociceptive Neurons and Transient Receptor Potential Channels for the Treatment of Migraine.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
Although feverfew has been used for centuries to treat pain and headaches and is recommended for migraine treatment, the mechanism for its protective action remains unknown. Migraine is triggered by calcitonin gene-related peptide (CGRP) release from trigeminal neurons. Peptidergic sensory neurons express a series of transient receptor potential (TRP) channels, including the ankyrin 1 (TRPA1) channel. Recent findings have identified agents either inhaled from the environment or produced endogenously that are known to trigger migraine or cluster headache attacks, such as TRPA1 simulants. A major constituent of feverfew, parthenolide, may interact with TRPA1 nucleophilic sites, suggesting that feverfew's antimigraine effect derives from its ability to target TRPA1. We found that parthenolide stimulates recombinant (transfected cells) or natively expressed (rat/mouse trigeminal neurons) TRPA1, where it, however, behaves as a partial agonist. Furthermore, in rodents, after initial stimulation, parthenolide desensitizes the TRPA1 channel and renders peptidergic TRPA1-expressing nerve terminals unresponsive to any stimulus. This effect of parthenolide abrogates nociceptive responses evoked by stimulation of peripheral trigeminal endings. TRPA1 targeting and neuronal desensitization by parthenolide inhibits CGRP release from trigeminal neurons and CGRP-mediated meningeal vasodilatation, evoked by either TRPA1 agonists or other unspecific stimuli. TRPA1 partial agonism, together with desensitization and nociceptor defunctionalization, ultimately resulting in inhibition of CGRP release within the trigeminovascular system, may contribute to the antimigraine effect of parthenolide.
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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.