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Effect of infralimbic cortex neural stimulation and the psychopharmacological interaction among glutamatergic and endocannabinoid systems in the chronic neuropathic pain modulation in rats

Grant number: 17/07209-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2017
Effective date (End): April 30, 2018
Field of knowledge:Health Sciences - Medicine - Psychiatry
Principal Investigator:Renato Leonardo de Freitas
Grantee:Thais Lohanny Moura Pacheco
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:13/12916-0 - Role of endocannabinoid, glutamatergic and endovanilloid systems of medial prefrontal cortex in neuropathic pain model and investigation of neurological disorders and chronic pain comorbidity, AP.JP

Abstract

Due to the lack of studies that investigate the neuroanatomical and psychopharmacological basis of chronic pain and the involvement of cortical areas of the medial prefrontal cortex (mPFC), the present study will evaluate whether the infralimbic division (IL) of the mPFC is involved in the elaboration of chronic pain induced by chronic constriction of the sciatic nerve (CCI) in the neuropathic pain model. For this, a neurophysiological study will be carried out with the cortical area synapse blocking through the microinjection of cobalt chloride into the IL division of the mPFC, evaluating its effect on neuropathic pain. We will also use our multi-user (EMU) deep brain stimulation (DBS) to perform neurostimulation of the IL cortex (20¼A for 15s) of rats with neuropathic pain. The nociceptive test to be used is that of cold hypersensitivity (acetone test) and mechanical allodynia (von Frey), with which we will evaluate the mechanical and cold nociceptive threshold on the twenty-first day after induction of neuropathic pain by CCI. The next step, will be to investigate the pharmacological interaction between the endocannabinoid and glutamatergic systems in the IL cortex, by pretreatment with microinjections of increasing doses of AM-251 (selective CB1 receptor antagonist), followed by activation of the glutamatergic system with NMDA (agonist glutamatergic NMDA receptors); NMDA receptor blockade will also be performed by pre-treatment with increasing doses of LY235959 (selective NMDA receptor antagonist), followed by endocannabinoid activation through microinjection of anandamide (endocannabinoid agonist) into the IL cortex, evaluating the cold hypersensitivity and mechanical allodynia in an experimental model of neuropathic pain induced by chronic constriction of the sciatic nerve in Wistar rats. (AU)