TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

Maria Cristina Marrone; Annunziato Morabito; Michela Giustizieri; Valerio Chiurchiù; Alessandro Leuti; Marzia Mattioli; Sara Marinelli; Loredana Riganti; Marta Lombardi; Emanuele Murana; Antonio Totaro; Daniele Piomelli; Davide Ragozzino; Sergio Oddi; Mauro Maccarrone; Claudia Verderio; Silvia Marinelli

doi:10.1038/ncomms15292

TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

Maria Cristina Marrone, Annunziato Morabito, Michela Giustizieri, Valerio Chiurchiù, Alessandro Leuti, Marzia Mattioli, Sara Marinelli, Loredana Riganti, Marta Lombardi, Emanuele Murana, Antonio Totaro, Daniele Piomelli, Davide Ragozzino, Sergio Oddi, Mauro Maccarrone, Claudia Verderio, Silvia Marinelli

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Abstract

The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication.

Original language	English
Article number	15292
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15292
Publication status	Published - Jan 1 2017

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Marrone, M. C., Morabito, A., Giustizieri, M., Chiurchiù, V., Leuti, A., Mattioli, M., Marinelli, S., Riganti, L., Lombardi, M., Murana, E., Totaro, A., Piomelli, D., Ragozzino, D., Oddi, S., Maccarrone, M., Verderio, C., & Marinelli, S. (2017). TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice. Nature Communications, 8, [15292]. https://doi.org/10.1038/ncomms15292

TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice. / Marrone, Maria Cristina; Morabito, Annunziato; Giustizieri, Michela; Chiurchiù, Valerio ; Leuti, Alessandro; Mattioli, Marzia; Marinelli, Sara; Riganti, Loredana; Lombardi, Marta; Murana, Emanuele; Totaro, Antonio; Piomelli, Daniele; Ragozzino, Davide; Oddi, Sergio ; Maccarrone, Mauro; Verderio, Claudia; Marinelli, Silvia.

In: Nature Communications, Vol. 8, 15292, 01.01.2017.

Research output: Contribution to journal › Article › peer-review

Marrone, MC, Morabito, A, Giustizieri, M, Chiurchiù, V , Leuti, A, Mattioli, M, Marinelli, S, Riganti, L, Lombardi, M, Murana, E, Totaro, A, Piomelli, D, Ragozzino, D, Oddi, S , Maccarrone, M, Verderio, C & Marinelli, S 2017, 'TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice', Nature Communications, vol. 8, 15292. https://doi.org/10.1038/ncomms15292

Marrone, Maria Cristina ; Morabito, Annunziato ; Giustizieri, Michela ; Chiurchiù, Valerio ; Leuti, Alessandro ; Mattioli, Marzia ; Marinelli, Sara ; Riganti, Loredana ; Lombardi, Marta ; Murana, Emanuele ; Totaro, Antonio ; Piomelli, Daniele ; Ragozzino, Davide ; Oddi, Sergio ; Maccarrone, Mauro ; Verderio, Claudia ; Marinelli, Silvia. / TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice. In: Nature Communications. 2017 ; Vol. 8.

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abstract = "The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication.",

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AU - Leuti, Alessandro

AU - Mattioli, Marzia

AU - Marinelli, Sara

AU - Riganti, Loredana

AU - Lombardi, Marta

AU - Murana, Emanuele

AU - Totaro, Antonio

AU - Piomelli, Daniele

AU - Ragozzino, Davide

AU - Oddi, Sergio

AU - Maccarrone, Mauro

AU - Verderio, Claudia

AU - Marinelli, Silvia

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N2 - The capsaicin receptor TRPV1 has been widely characterized in the sensory system as a key component of pain and inflammation. A large amount of evidence shows that TRPV1 is also functional in the brain although its role is still debated. Here we report that TRPV1 is highly expressed in microglial cells rather than neurons of the anterior cingulate cortex and other brain areas. We found that stimulation of microglial TRPV1 controls cortical microglia activation per se and indirectly enhances glutamatergic transmission in neurons by promoting extracellular microglial microvesicles shedding. Conversely, in the cortex of mice suffering from neuropathic pain, TRPV1 is also present in neurons affecting their intrinsic electrical properties and synaptic strength. Altogether, these findings identify brain TRPV1 as potential detector of harmful stimuli and a key player of microglia to neuron communication.

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TRPV1 channels are critical brain inflammation detectors and neuropathic pain biomarkers in mice

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