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Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine

BACKGROUND: Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive ph...

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Autores principales: Franceschini, Alessia, Nair, Asha, Bele, Tanja, van den Maagdenberg, Arn MJM, Nistri, Andrea, Fabbretti, Elsa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511260/
https://www.ncbi.nlm.nih.gov/pubmed/23171280
http://dx.doi.org/10.1186/1471-2202-13-143
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author Franceschini, Alessia
Nair, Asha
Bele, Tanja
van den Maagdenberg, Arn MJM
Nistri, Andrea
Fabbretti, Elsa
author_facet Franceschini, Alessia
Nair, Asha
Bele, Tanja
van den Maagdenberg, Arn MJM
Nistri, Andrea
Fabbretti, Elsa
author_sort Franceschini, Alessia
collection PubMed
description BACKGROUND: Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined. RESULTS: KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells) strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed. CONCLUSIONS: Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons.
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spelling pubmed-35112602012-12-01 Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine Franceschini, Alessia Nair, Asha Bele, Tanja van den Maagdenberg, Arn MJM Nistri, Andrea Fabbretti, Elsa BMC Neurosci Research Article BACKGROUND: Enhanced activity of trigeminal ganglion neurons is thought to underlie neuronal sensitization facilitating the onset of chronic pain attacks, including migraine. Recurrent headache attacks might establish a chronic neuroinflammatory ganglion profile contributing to the hypersensitive phenotype. Since it is difficult to study this process in vivo, we investigated functional crosstalk between macrophages and sensory neurons in primary cultures from trigeminal sensory ganglia of wild-type (WT) or knock-in (KI) mice expressing the Cacna1a gene mutation (R192Q) found in familial hemiplegic migraine-type 1. After studying the number and morphology of resident macrophages in culture, the consequences of adding host macrophages on macrophage phagocytosis and membrane currents mediated by pain-transducing P2X3 receptors on sensory neurons were examined. RESULTS: KI ganglion cultures constitutively contained a larger number of active macrophages, although no difference in P2X3 receptor expression was found. Co-culturing WT or KI ganglia with host macrophages (active as much as resident cells) strongly stimulated single cell phagocytosis. The same protocol had no effect on P2X3 receptor expression in WT or KI co-cultures, but it largely enhanced WT neuron currents that grew to the high amplitude constitutively seen for KI neurons. No further potentiation of KI neuronal currents was observed. CONCLUSIONS: Trigeminal ganglion cultures from a genetic mouse model of migraine showed basal macrophage activation together with enhanced neuronal currents mediated by P2X3 receptors. This phenotype could be replicated in WT cultures by adding host macrophages, indicating an important functional crosstalk between macrophages and sensory neurons. BioMed Central 2012-11-21 /pmc/articles/PMC3511260/ /pubmed/23171280 http://dx.doi.org/10.1186/1471-2202-13-143 Text en Copyright ©2012 Franceschini et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Franceschini, Alessia
Nair, Asha
Bele, Tanja
van den Maagdenberg, Arn MJM
Nistri, Andrea
Fabbretti, Elsa
Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine
title Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine
title_full Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine
title_fullStr Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine
title_full_unstemmed Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine
title_short Functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine
title_sort functional crosstalk in culture between macrophages and trigeminal sensory neurons of a mouse genetic model of migraine
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511260/
https://www.ncbi.nlm.nih.gov/pubmed/23171280
http://dx.doi.org/10.1186/1471-2202-13-143
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