1. The blockade of the transient receptor potential vanilloid type 1 and fatty acid amide hydrolase decreases symptoms and central sequelae in the medial prefrontal cortex of neuropathic rats
- Author
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Giulia Bellini, Enza Palazzo, Luisa Gatta, Vincenzo Di Marzo, Sabatino Maione, Ida Marabese, Livio Luongo, Vito de Novellis, Dario Siniscalco, Daniela Vita, Maria De Chiaro, Francesco Rossi, Serena Boccella, Fabiana Piscitelli, DE NOVELLIS, Vito, Vita, D, Gatta, L, Luongo, Livio, Bellini, Giulia, De Chiaro, M, Marabese, Ida, Siniscalco, D, Boccella, S, Piscitelli, F, Di Marzo, V, Palazzo, Enza, Rossi, Francesco, and Maione, Sabatino
- Subjects
Male ,medicine.medical_specialty ,Serotonin ,Microinjections ,Microdialysis ,TRPV1 ,Prefrontal Cortex ,TRPV Cation Channels ,Arachidonic Acids ,Amidohydrolases ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Piperidines ,Fatty acid amide hydrolase ,Internal medicine ,lcsh:Pathology ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Prefrontal cortex ,Electrodes ,Neurons ,business.industry ,Research ,Mononeuropathies ,Nociceptors ,Nerve injury ,URB597 ,Amygdala ,Electric Stimulation ,Electrophysiological Phenomena ,Rats ,Anesthesiology and Pain Medicine ,Endocrinology ,Allodynia ,chemistry ,nervous system ,Neuropathic pain ,Peripheral nerve injury ,Benzamides ,Molecular Medicine ,Pyrazoles ,Carbamates ,medicine.symptom ,business ,Neuroscience ,psychological phenomena and processes ,lcsh:RB1-214 - Abstract
Background: Neuropathic pain is a chronic disease resulting from dysfunction within the “pain matrix”. The basolateral amygdala (BLA) can modulate cortical functions and interactions between this structure and the medial prefrontal cortex (mPFC) are important for integrating emotionally salient information. In this study, we have investigated the involvement of the transient receptor potential vanilloid type 1 (TRPV1) and the catabolic enzyme fatty acid amide hydrolase (FAAH) in the morphofunctional changes occurring in the pre-limbic/infra-limbic (PL/IL) cortex in neuropathic rats. Results: The effect of N-arachidonoyl-serotonin (AA-5-HT), a hybrid FAAH inhibitor and TPRV1 channel antagonist, was tested on nociceptive behaviour associated with neuropathic pain as well as on some phenotypic changes occurring on PL/IL cortex pyramidal neurons. Those neurons were identified as belonging to the BLA-mPFC pathway by electrical stimulation of the BLA followed by hind-paw pressoceptive stimulus application. Changes in their spontaneous and evoked activity were studied in sham or spared nerve injury (SNI) rats before or after repeated treatment with AA-5-HT. Consistently with the SNI-induced changes in PL/IL cortex neurons which underwent profound phenotypic reorganization, suggesting a profound imbalance between excitatory and inhibitory responses in the mPFC neurons, we found an increase in extracellular glutamate levels, as well as the upregulation of FAAH and TRPV1 in the PL/IL cortex of SNI rats. Daily treatment with AA-5-HT restored cortical neuronal activity, normalizing the electrophysiological changes associated with the peripheral injury of the sciatic nerve. Finally, a single acute intra-PL/IL cortex microinjection of AA-5-HT transiently decreased allodynia more effectively than URB597 or I-RTX, a selective FAAH inhibitor or a TRPV1 blocker, respectively. Conclusion: These data suggest a possible involvement of endovanilloids in the cortical plastic changes associated with peripheral nerve injury and indicate that therapies able to normalize endovanilloid transmission may prove useful in ameliorating the symptoms and central sequelae associated with neuropathic pain.
- Published
- 2011