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. © 2012 The Author.

TRPV1-dependent and-independent alterations in the limbic cortex of neuropathic mice: Impact on glial caspases and pain perception

Imperatore R.;
2012-01-01

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. © 2012 The Author.
2012
CB; 1; endocannabinoid; FAAH; neuropathic pain; TRPV1; Animals; Arachidonic Acids; Behavior, Animal; Blotting, Western; Caspases; Cerebral Cortex; Endocannabinoids; Ethanolamines; Evoked Potentials; Extracellular Space; Glycerides; Immunohistochemistry; Limbic System; Male; Mice; Mice, Inbred C57BL; Neuralgia; Neuroglia; Pain Perception; Postural Balance; RNA; Real-Time Polymerase Chain Reaction; Receptors, Glutamate; Sciatic Neuropathy; TRPV Cation Channels
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12070/42873
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