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

• Published in: Nature communications Vol. 8; no. 1; p. 15292
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.05.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/21; 13/31; 13/51; 45; 45/88; 631/378/2596/1953; 631/378/548/2589; 82; 82/80; 9/74; Animals; Biomarkers; Biomarkers - metabolism; Brain research; Cell-Derived Microparticles; Communication; Encephalitis - metabolism; Excitatory Postsynaptic Potentials; Humanities and Social Sciences; Male; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microglia - metabolism; multidisciplinary; Nervous system; Neuralgia - metabolism; Neurons; Neurons - metabolism; Neurons - physiology; Neurosciences; Pain; Physiology; Science; Science (multidisciplinary); Synaptic Transmission; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Rome Italy; Italy
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms15292

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. TRPV1 is known to be expressed in peripheral structures and the spinal cord, especially for pain processing. Here the authors show that in the brain, in particular the anterior cingulate cortex, TRPV1 is functionally expressed in microglia; stimulation of TRPV1 activates microglia, which in turn affects glutamatergic neurotransmission.