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

BMC Neuroscience

Research Article

Tanja Bele¹  Andrea Nistri²  Asha Nair²  Elsa Fabbretti³  Alessia Franceschini⁴  Arn MJM van den Maagdenberg⁵ 

[1] Center for Biomedical Sciences and Engineering, University of Nova Gorica, SI-5000, Nova, Gorica, Slovenia;Department of Neuroscience and Italian Institute of Technology Unit, International School for Advanced Studies (SISSA), Via Bonomea 265, 34136, Trieste, Italy;Department of Neuroscience and Italian Institute of Technology Unit, International School for Advanced Studies (SISSA), Via Bonomea 265, 34136, Trieste, Italy;Center for Biomedical Sciences and Engineering, University of Nova Gorica, SI-5000, Nova, Gorica, Slovenia;Department of Neuroscience and Italian Institute of Technology Unit, International School for Advanced Studies (SISSA), Via Bonomea 265, 34136, Trieste, Italy;Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, Ferrara, Italy;Departments of Human Genetics & Neurology, Leiden University Medical Centre, 2300, Leiden, RC, The Netherlands;

关键词: P2X3 receptor;    Purinergic receptor;    Pain;    Neuroinflammation;    ATP;    Sensitization;   

DOI  :  10.1186/1471-2202-13-143

 received in 2012-05-29, accepted in 2012-10-31,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundEnhanced 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.ResultsKI 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.ConclusionsTrigeminal 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.

【 授权许可】

Unknown   
© Franceschini et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. 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.