We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
TRPV1-Dependent and -Independent Alterations in the Limbic Cortex of Neuropathic Mice: Impact on Glial Caspases and Pain Perception.
- Authors
Giordano, Catia; Cristino, Luigia; Luongo, Livio; Siniscalco, Dario; Petrosino, Stefania; Piscitelli, Fabiana; Marabese, Ida; Gatta, Luisa; Rossi, Francesca; Imperatore, Roberta; Palazzo, Enza; de Novellis, Vito; Di Marzo, Vincenzo; Maione, Sabatino
- Abstract
During neuropathic pain, caspases are activated in the limbic cortex. We investigated the role of TRPV1 channels and glial caspases in the mouse prelimbic and infralimbic (PL-IL) cortex after spared nerve injury (SNI). Reverse transcriptase-polymerase chain reaction, western blots, and immunfluorescence showed overexpression of several caspases in the PL-IL cortex 7 days postinjury. Caspase-3 release and upregulation of AMPA receptors in microglia, caspase-1 and IL-1β release in astrocytes, and upregulation of Il-1 receptor-1, TRPV1, and VGluT1 in glutamatergic neurons, were also observed. Of these alterations, only those in astrocytes persisted in SNI Trpv1−/− mice. A pan-caspase inhibitor, injected into the PL-IL cortex, reduced mechanical allodynia, this effect being reduced but not abolished in Trpv1−/− mice. Single-unit extracellular recordings in vivo following electrical stimulation of basolateral amygdala or application of pressure on the hind paw, showed increased excitatory pyramidal neuron activity in the SNI PL-IL cortex, which also contained higher levels of the endocannabinoid 2-arachidonoylglycerol. Intra-PL-IL cortex injection of mGluR5 and NMDA receptor antagonists and AMPA exacerbated, whereas TRPV1 and AMPA receptor antagonists and a CB1 agonist inhibited, allodynia. We suggest that SNI triggers both TRPV1-dependent and independent glutamate- and caspase-mediated cross-talk among IL-PL cortex neurons and glia, which either participates or counteracts pain.
- Publication
Cerebral Cortex, 2012, Vol 22, Issue 11, p2495
- ISSN
1047-3211
- Publication type
Article
- DOI
10.1093/cercor/bhr328