ArticlePloS one2013
The mechanism of functional up-regulation of P2X3 receptors of trigeminal sensory neurons in a genetic mouse model of familial hemiplegic migraine type 1 (FHM-1).
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Role of ATP in migraine mechanisms: focus on P2X3 receptors.The journal of headache and pain · 2023Review
- Migraine and neuroinflammation: the inflammasome perspective.The journal of headache and pain · 2021Review
- Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing.International journal of molecular sciences · 2021Article
- Overexpressed NaFrontiers in cellular neuroscience · 2021Article
- Genetic mouse models of migraine.The journal of headache and pain · 2019Review
- Trigeminovascular calcitonin gene-related peptide function in Cacna1a R192Q-mutated knock-in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Mouse Models of Familial Hemiplegic Migraine for Studying Migraine Pathophysiology.Current neuropharmacology · 2019Review
- In situ imaging reveals properties of purinergic signalling in trigeminal sensory ganglia in vitro.Purinergic signalling · 2017Article
- Article
- Brain natriuretic peptide constitutively downregulates P2X3 receptors by controlling their phosphorylation state and membrane localization.Molecular pain · 2015Article
- The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors.Science translational medicine · 2015Article
- The purinergic system and glial cells: emerging costars in nociception.BioMed research international · 2014Review
- Expression and characterization of purinergic receptors in rat middle meningeal artery-potential role in migraine.PloS one · 2014Article
- Desensitization properties of P2X3 receptors shaping pain signaling.Frontiers in cellular neuroscience · 2013Review
- Immobilization-induced hypersensitivity associated with spinal cord sensitization during cast immobilization and after cast removal in rats.The journal of physiological sciences : JPS · 2013Article
- B-type natriuretic peptide-induced delayed modulation of TRPV1 and P2X3 receptors of mouse trigeminal sensory neurons.PloS one · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
A knock-in (KI) mouse model of FHM-1 expressing the R192Q missense mutation of the Cacna1a gene coding for the α1 subunit of CaV2.1 channels shows, at the level of the trigeminal ganglion, selective functional up-regulation of ATP -gated P2X3 receptors of sensory neurons that convey nociceptive signals to the brainstem. Why P2X3 receptors are constitutively more responsive, however, remains unclear as their membrane expression and TRPV1 nociceptor activity are the same as in wildtype (WT) neurons. Using primary cultures of WT or KI trigeminal ganglia, we investigated whether soluble compounds that may contribute to initiating (or maintaining) migraine attacks, such as TNFα, CGRP, and BDNF, might be responsible for increasing P2X3 receptor responses. Exogenous application of TNFα potentiated P2X3 receptor-mediated currents of WT but not of KI neurons, most of which expressed both the P2X3 receptor and the TNFα receptor TNFR2. However, sustained TNFα neutralization failed to change WT or KI P2X3 receptor currents. This suggests that endogenous TNFα does not regulate P2X3 receptor responses. Nonetheless, on cultures made from both genotypes, exogenous TNFα enhanced TRPV1 receptor-mediated currents expressed by a few neurons, suggesting transient amplification of TRPV1 nociceptor responses. CGRP increased P2X3 receptor currents only in WT cultures, although prolonged CGRP receptor antagonism or BDNF neutralization reduced KI currents to WT levels. Our data suggest that, in KI trigeminal ganglion cultures, constitutive up-regulation of P2X3 receptors probably is already maximal and is apparently contributed by basal CGRP and BDNF levels, thereby rendering these neurons more responsive to extracellular ATP.
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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.