ArticlePurinergic signalling2016
Nucleotide homeostasis and purinergic nociceptive signaling in rat meninges in migraine-like conditions.
Article in Purinergic signalling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Involvement of adenosine signaling pathway in migraine pathophysiology: a systematic review of preclinical studies.The journal of headache and pain · 2022Pooled it
- Targeting glial-orchestrated neuroinflammation in migraine pathophysiology.The journal of headache and pain · 2026Review
- The Role of Purinergic Mechanisms in the Excitability of Trigeminal Afferents of Rats with Prenatal Hyperhomocysteinemia.Biomolecules · 2025Article
- Potent painkiller from spider venom antagonizes P2X3 receptors without dysgeusia.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Astrocyte-Microglia Crosstalk: A Novel Target for the Treatment of Migraine.Aging and disease · 2024Review
- Glia Signaling and Brain Microenvironment in Migraine.Molecular neurobiology · 2023Review
- Effects of Nitric Oxide on the Activity of P2X and TRPV1 Receptors in Rat Meningeal Afferents of the Trigeminal Nerve.International journal of molecular sciences · 2023Article
- Role of ATP in migraine mechanisms: focus on P2X3 receptors.The journal of headache and pain · 2023Review
- B-Cell Targeted Therapies in Patients with Multiple Sclerosis and Incidence of Headache: A Systematic Review and Meta-Analysis.Journal of personalized medicine · 2022Review
- Review
- Microglial amyloid beta clearance is driven by PIEZO1 channels.Journal of neuroinflammation · 2022Article
- The role of the meningeal lymphatic system in local meningeal inflammation and trigeminal nociception.Scientific reports · 2022Article
- Inhibiting Endocannabinoid Hydrolysis as Emerging Analgesic Strategy Targeting a Spectrum of Ion Channels Implicated in Migraine Pain.International journal of molecular sciences · 2022Review
- Involvement of P2X7 receptors in chronic pain disorders.Purinergic signalling · 2022Review
- Lasmiditan and 5-Hydroxytryptamine in the rat trigeminal system; expression, release and interactions with 5-HTThe journal of headache and pain · 2022Article
- Testing the Role of Glutamate NMDA Receptors in Peripheral Trigeminal Nociception Implicated in Migraine Pain.International journal of molecular sciences · 2022Article
- Functional Coupling between the P2XInternational journal of molecular sciences · 2021Article
- DecipheringFrontiers in cellular neuroscience · 2021Article
- P2X7 receptors exert a permissive effect on the activation of presynaptic AMPA receptors in rat trigeminal caudal nucleus glutamatergic nerve terminals.The journal of headache and pain · 2020Article
- The Emerging Role of Mechanosensitive Piezo Channels in Migraine Pain.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular ATP is suspected to contribute to migraine pain but regulatory mechanisms controlling pro-nociceptive purinergic mechanisms in the meninges remain unknown. We studied the peculiarities of metabolic and signaling pathways of ATP and its downstream metabolites in rat meninges and in cultured trigeminal cells exposed to the migraine mediator calcitonin gene-related peptide (CGRP). Under resting conditions, meningeal ATP and ADP remained at low nanomolar levels, whereas extracellular AMP and adenosine concentrations were one-two orders higher. CGRP increased ATP and ADP levels in meninges and trigeminal cultures and reduced adenosine concentration in trigeminal cells. Degradation rates for exogenous nucleotides remained similar in control and CGRP-treated meninges, indicating that CGRP triggers nucleotide release without affecting nucleotide-inactivating pathways. Lead nitrate-based enzyme histochemistry of whole mount meninges revealed the presence of high ATPase, ADPase, and AMPase activities, primarily localized in the medial meningeal artery. ATP and ADP induced large intracellular Ca(2+) transients both in neurons and in glial cells whereas AMP and adenosine were ineffective. In trigeminal glia, ATP partially operated via P2X7 receptors. ATP, but not other nucleotides, activated nociceptive spikes in meningeal trigeminal nerve fibers providing a rationale for high degradation rate of pro-nociceptive ATP. Pro-nociceptive effect of ATP in meningeal nerves was reproduced by α,β-meATP operating via P2X3 receptors. Collectively, extracellular ATP, which level is controlled by CGRP, can persistently activate trigeminal nerves in meninges which considered as the origin site of migraine headache. These data are consistent with the purinergic hypothesis of migraine pain and suggest new targets against trigeminal pain.
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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.