| Grant number: | 13/12916-0 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Start date: | June 01, 2014 |
| End date: | May 31, 2019 |
| Field of knowledge: | Health Sciences - Medicine - Psychiatry |
| Principal Investigator: | Renato Leonardo de Freitas |
| Grantee: | Renato Leonardo de Freitas |
| Host Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| City of the host institution: | Ribeirão Preto |
| Associated researchers: | Norberto Cysne Coimbra ; Sérgio Henrique Ferreira |
| Associated research grant(s): | 14/11869-0 - Multi-use equipment approved in grant 2013/12916-0: deep brain stimulation (DBS) (Thomas mini matrix system - Thomas recording GmbH® - Winchester Strasse - Giessen - Germany), AP.EMU |
| Associated scholarship(s): | 14/07902-2 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity, BP.JP |
Abstract
The aim of our study is to investigate the medial prefrontal cortex (MPFC), in modulation of chronic pain through possible activation of descendent pathway during the neuropathic pain induced by chronic constriction of the sciatic nerve (CCSN). The role of MPFC and endogenous pain modulatory systems like periaqueductal gray matter (PAG), magnum raphe nucleus (MRN) and locus coeruleus (LC) will evaluate after stimulation of CCSN. Immunohistochemistry will perform at 7, 14, 21 and 28 days after stimulation of CCSN to identify c-Fos protein and NMDA glutamate, endocannabinoid CB1 and TRPV1 receptors, analyzing the neuromolecular activity. In addition, 28 days after the CCSN, the MPFC, PAG, MRN and LC will be separate and Western Blotting will perform to evaluate if chronic pain increases the expression of NMDA, CB1 and TRPV1 receptors. Furthermore, to verify the possible increase of amount of protein to these receptors is also accompanied by increase of mRNA in MPFC, SCP, NMR and LC will be used the technique of real-time polymerase chain reaction (RT-PCR). The next step will be the neurostimulation of MPFC through of technique of deep brain stimulation (DBS) evaluating its effect on the neuropathic pain, and also record the activity of neuronal nuclei of endogenous pain inhibitory system. The nociceptive test will be used is mechanical allodynia, the von Frey at 7, 14, 21 and 28 days after stimulation of CCSN. After evaluate the involvement of the activation of the cortical and the activation of NMDA, CB1 e TRPV1 receptors in the NP, the pharmacological interaction between the endocannabinoid and the glutamatergic and endocannabinoid and endovaniloid systems of MPFC will investigate. Furthermore, the comorbidity depression, anxiety and panic in rodents with chronic pain will investigate. The neurophysiological (neurostimulation by DBS) and neuropharmacological procedures (pharmacological interactions) will be also investigate. The animals will subject to experimental model of depression and anxiety/panic 21 days after the CCSN to evaluate the relation between depression or anxiety/panic disorders and neuropathic pain in Wistar rat. (AU)
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