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Role of glutamatergic, endocannabinoid and endovaniloid systems of medial pre-frontal cortex in neurophatic pain model: Investigation of panic and chronic pain comorbidity

Grant number: 12/25167-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2013
Effective date (End): August 31, 2017
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal researcher:Norberto Cysne Coimbra
Grantee:Priscila Medeiros de Freitas
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The aim of our study is to investigate the neuroanatomical and pharmacological basis of chronic pain. Cortical areas, like prelimbic (PL) and infralimbic (IL) divisions of medial prefrontal cortex (MPFC), will investigate 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 PL, IL and endogenous pain modulatory systems in periaqueductal gray matter, magnum raphe nucleus and locus coeruleus will evaluate after stimulation of CCSN. Immunohistochemistry will perform at 2, 7, 14 and 21 days after stimulation of CCSN to identify c-Fos protein and NMDA glutamate, endocannabinoid CB1 and TRPV1 endovaniloid receptors, analyzing the neuromolecular activity after 2, 7, 14 and 21 days of induction of CCSN. The nociceptive test that will be used is mechanical allodynia, the von Frey. After evaluate the involvement of the activation of the cortical and brainstem areas and the activation of NMDA, CB1 e TRPV1 receptors in the neuropathic pain, the pharmacological interaction between the endocannabinoid and the glutamatergic systems of PL and IL will investigate. Pretreatment doses of AM-251 (CB1 antagonist receptors) will follow by activation of glutamatergic system through of microinjection of l-glutamate (glutamatergic agonist). PL or IL-pretreatment with NMDA receptors antagonist LY23595 (NMDA antagonist receptors) will perform, followed by activation of PL or IL with endocannabinoid anandamide (endocannabinoid agonist). In the next study, capsazepine (TRPV1 antagonist) will administer in PL or IL, followed by activation of endocannabinoid system through of microinjection of anandamide in PL or IL. PL or IL-pretreatment with CB1 receptors antagonist will perform by microinjection of AM251 (CB1 receptors antagonist) followed by activation of endovaniloid system in PL or IL through microinjection of capsaicin (endovaniloid agonist) to evaluate the involvement of cortical areas in the neuropathic pain. Furthermore, the comorbidity panic and fear in rodents with neuropathy pain will investigate. The animals will subject to aggressive confrontation with constrictor snake after seven days of CCSN activation to evaluate the relation between panic/anxiety disorders and neuropathic pain.

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Scientific publications (14)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MEDEIROS, PRISCILA; DOS SANTOS, IEDA REGINA; MATIAS JUNIOR, IVAIR; PALAZZO, ENZA; DA SILVA, JOSE APARECIDO; MACHADO, HELIO RUBENS; FERREIRA, SERGIO HENRIQUE; MAIONE, SABATINO; COIMBRA, NORBERTO CYSNE; DE FREITAS, RENATO LEONARDO. An Adapted Chronic Constriction Injury of the Sciatic Nerve Produces Sensory, Affective, and Cognitive Impairments: A Peripheral Mononeuropathy Model for the Study of Comorbid Neuropsychiatric Disorders Associated with Neuropathic Pain in Rats. PAIN MEDICINE, v. 22, n. 2, p. 338-351, . (11/19670-0, 13/08216-2, 13/12916-0, 17/13560-5, 14/11869-0, 12/25167-2, 14/07902-2, 09/17258-5)
DE FREITAS, RENATO LEONARDO; MEDEIROS, PRISCILA; KHAN, ASMAT ULLAH; COIMBRA, NORBERTO CYSNE. mu(1)-Opioid receptors in the dorsomedial and ventrolateral columns of the periaqueductal grey matter are critical for the enhancement of post-ictal antinociception. Synapse, v. 70, n. 12, p. 519-530, . (09/00668-6, 13/12916-0, 12/25167-2, 09/17258-5, 14/11869-0)
MEDEIROS, P.; DE FREITAS, R. L.; SILVA, M. O.; COIMBRA, N. C.; MELO-THOMAS, L.. CB1 CANNABINOID RECEPTOR-MEDIATED ANANDAMIDE SIGNALING MECHANISMS OF THE INFERIOR COLLICULUS MODULATE THE HALOPERIDOL-INDUCED CATALEPSY. Neuroscience, v. 337, p. 17-26, . (13/12916-0, 11/01409-4, 12/25167-2, 14/11869-0)
DE FREITAS, RENATO LEONARDO; MEDEIROS, PRISCILA; DA SILVA, JULIANA ALMEIDA; DE OLIVEIRA, RITHIELE CRISTINA; DE OLIVEIRA, RICARDO; ULLAH, FARHAD; KHAN, ASMAT ULLAH; COIMBRA, NORBERTO CYSNE. THE mu(1)-OPIOID RECEPTOR AND 5-HT2A- AND 5HT(2C)-SEROTONERGIC RECEPTORS OF THE LOCUS COERULEUS ARE CRITICAL IN ELABORATING HYPOALGESIA INDUCED BY TONIC AND TONIC-CLONIC SEIZURES. Neuroscience, v. 336, p. 133-145, . (09/00668-6, 13/12916-0, 09/02458-9, 12/25167-2, 11/09850-1, 09/17258-5, 15/10313-1, 14/11869-0)
CALVO, FABRICIO; ALMADA, RAFAEL CARVALHO; DOS ANJOS-GARCIA, TAYLLON; FALCONI-SOBRINHO, LUIZ LUCIANO; PASCHOALIN-MAURIN, TATIANA; BAZAGLIA-DE-SOUSA, GUILHERME; MEDEIROS, PRISCILA; DA SILVA, JULIANA ALMEIDA; LOBAO-SOARES, BRUNO; COIMBRA, NORBERTO CYSNE. Panicolytic-like effect of mu(1)-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers. JOURNAL OF PSYCHOPHARMACOLOGY, v. 33, n. 5, p. 577-588, . (12/03798-0, 09/02458-9, 07/01174-1, 12/25167-2, 13/10984-8, 17/13560-5, 17/11855-8, 12/22681-7, 15/10313-1)
MEDEIROS, PRISCILA; OLIVEIRA-SILVA, MARIANA; NEGRINI-FERRARI, SYLMARA ESTHER; MEDEIROS, ANA CAROLINA; ELIAS-FILHO, DAOUD HIBRAIM; COIMBRA, NORBERTO CYSNE; DE FREITAS, RENATO LEONARDO. CB1-cannabinoid-, TRPV1-vanilloid- and NMDA-glutamatergic-receptor-signalling systems interact in the prelimbic cerebral cortex to control neuropathic pain symptoms. Brain Research Bulletin, v. 165, p. 118-128, . (17/13560-5, 09/17258-5, 12/25167-2, 14/11869-0, 14/07902-2, 13/12916-0)
MEDEIROS, PRISCILA; NEGRINI-FERRARI, SYLMARA ESTHER; PALAZZO, ENZA; MAIONE, SABATINO; FERREIRA, SERGIO HENRIQUE; DE FREITAS, RENATO LEONARDO; COIMBRA, NORBERTO CYSNE. N-methyl-d-aspartate Receptors in the Prelimbic Cortex are Critical for the Maintenance of Neuropathic Pain. Neurochemical Research, v. 44, n. 9, p. 2068-2080, . (14/07902-2, 13/12916-0, 12/25167-2, 17/13560-5, 09/17258-5, 11/19670-0, 13/08216-2, 14/11869-0)
P. MEDEIROS; I.R. DOS SANTOS; A.C. MEDEIROS; J.A. DA SILVA; S.H. FERREIRA; R.L. DE FREITAS; N.C. COIMBRA. Indomethacin attenuates mechanical allodynia during the organization but not the maintenance of the peripheral neuropathic pain induced by nervus ischiadicus chronic constriction injury. Brazilian Journal of Medical and Biological Research, v. 53, n. 5, p. -, . (09/17258-5, 13/12916-0, 17/13560-5, 12/25167-2, 11/19670-0, 14/07902-2, 14/11869-0, 13/08216-2)
CALVO, FABRICIO; ALMADA, RAFAEL CARVALHO; DA SILVA, JULIANA ALMEIDA; MEDEIROS, PRISCILA; SOARES, JR., RAIMUNDO DA SILVA; DE PAIVA, YARA BEZERRA; RONCON, CAMILA MARRONI; COIMBRA, NORBERTO CYSNE. The Blockade of mu(1)- and kappa-Opioid Receptors in the Inferior Colliculus Decreases the Expression of Panic Attack-Like Behaviours Induced by Chemical Stimulation of the Dorsal Midbrain. NEUROPSYCHOBIOLOGY, v. 78, n. 4, p. 218-228, . (09/54014-7, 12/23238-0, 15/10313-1, 09/02458-9, 07/01174-1, 12/25167-2, 12/03798-0, 17/13560-5, 12/22681-7)
MATIAS JUNIOR, IVAIR; MEDEIROS, PRISCILA; DE FREITA, RENATO LEONARDO; VICENTE-CESAR, HILTON; FERREIRA JUNIOR, JOSE RANIERY; MACHADO, HELIO RUBENS; MENEZES-REIS, RAFAEL. Effective Parameters for Gait Analysis in Experimental Models for Evaluating Peripheral Nerve Injuries in Rats. NEUROSPINE, v. 16, n. 2, p. 305-316, . (14/07902-2, 13/12916-0, 12/25167-2, 09/17258-5, 13/10543-1, 14/11869-0)
CALVO, FABRICIO; LOBAO-SOARES, BRUNO; DE FREITAS, RENATO LEONARDO; PASCHOALIN-MAURIN, TATIANA; DOS ANJOS-GARCIA, TAYLLON; MEDEIROS, PRISCILA; DA SILVA, JULIANA ALMEIDA; LOVICK, THELMA ANDERSON; COIMBRA, NORBERTO CYSNE. The endogenous opioid system modulates defensive behavior evoked by Crotalus durissus terrificus: Panicolytic-like effect of intracollicular non-selective opioid receptors blockade. JOURNAL OF PSYCHOPHARMACOLOGY, v. 33, n. 1, p. 51-61, . (14/11869-0, 07/01174-1, 15/10313-1, 17/11855-8, 09/02458-9, 12/03798-0, 13/12916-0, 12/25167-2)
NEGRINI-FERRARI, SYLMARA ESTHER; MEDEIROS, PRISCILA; MALVESTIO, RAFAEL BRAGHETTO; SILVA, MARIANA DE OLIVEIRA; MEDEIROS, ANA CAROLINA; COIMBRA, NORBERTO CYSNE; MACHADO, HELIO RUBENS; DE FREITAS, RENATO LEONARDO. The primary motor cortex electrical and chemical stimulation attenuates the chronic neuropathic pain by activation of the periaqueductal grey matter: The role of NMDA receptors. Behavioural Brain Research, v. 415, . (14/07902-2, 13/12916-0, 14/11869-0, 12/25167-2, 17/13560-5, 09/17258-5)
MEDEIROS, ANA C.; MEDEIROS, PRISCILA; FREITAS, RENATO L.; SILVA JUNIOR, PEDRO ISMAEL; COIMBRA, NORBERTO C.; DOS SANTOS, WAGNER F.. Acanthoscurria gomesiana spider-derived synthetic mygalin in the dorsal raphe nucleus modulates acute and chronic pain. JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, v. 35, n. 10, . (09/54014-7, 17/13560-5, 13/12916-0, 12/25167-2, 09/17258-5, 14/11869-0)
MALVESTIO, R. B.; MEDEIROS, P.; NEGRINI-FERRARI, S. E.; OLIVEIRA-SILVA, M.; MEDEIROS, A. C.; PADOVAN, C. M.; LUONGO, L.; MAIONE, S.; COIMBRA, N. C.; DE FREITAS, R. L.. Cannabidiol in the prelimbic cortex modulates the comorbid condition between the chronic neuropathic pain and depression-like behaviour in rats: The role of medial prefrontal cortex 5-HT1A and CB1 receptors. Brain Research Bulletin, v. 174, p. 323-338, . (14/07902-2, 12/25167-2, 17/13560-5, 09/17258-5, 14/26228-0, 14/16720-5)

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