title: TRPV1-dependent and -independent alterations in the limbic cortex of neuropathic mice: impact on glial caspases and pain perception.
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 CB(1) 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.
authors.affiliation: Endocannabinoid Research Group, Department of Experimental Medicine, Division of Pharmacology L. Donatelli, Second University of Naples, Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Giordano
authors.forename: Luigia
authors.initials: L
authors.lastname: Cristino
authors.forename: Livio
authors.initials: L
authors.lastname: Luongo
authors.forename: Dario
authors.initials: D
authors.lastname: Siniscalco
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Fabiana
authors.initials: F
authors.lastname: Piscitelli
authors.forename: Ida
authors.initials: I
authors.lastname: Marabese
authors.forename: Luisa
authors.initials: L
authors.lastname: Gatta
authors.forename: Francesca
authors.initials: F
authors.lastname: Rossi
authors.forename: Roberta
authors.initials: R
authors.lastname: Imperatore
authors.forename: Enza
authors.initials: E
authors.lastname: Palazzo
authors.forename: Vito
authors.initials: V
authors.lastname: de Novellis
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D063388:Endocannabinoids / Q000378:metabolism; D004983:Ethanolamines; D005071:Evoked Potentials / Q000502:physiology; D005110:Extracellular Space / Q000502:physiology; D005989:Glycerides / Q000378:metabolism; D007150:Immunohistochemistry; D008032:Limbic System / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D009457:Neuroglia / Q000201:enzymology*; D058748:Pain Perception / Q000502:physiology*; D004856:Postural Balance / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017470:Receptors, Glutamate / Q000502:physiology; D020426:Sciatic Neuropathy / Q000235:genetics / Q000503:physiopathology; D050916:TRPV Cation Channels / Q000235:genetics* / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; C022203:N-acylethanolamines; D017470:Receptors, Glutamate; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D012313:RNA; C094503:glyceryl 2-arachidonate; D020169:Caspases