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Association of dimethyl fumarate and pregabalin in the control of neuropathic pain in a murine model of multiple sclerosis

Grant number: 17/21878-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): January 01, 2018
Effective date (End): June 30, 2018
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Danielle Bernardes
Grantee:Amanda Garcia Hoelz
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Multiple Sclerosis (MS) is the most common autoimmune disease of the Central Nervous System (CNS), affecting mostly adult women. It is characterized by cognitive, motor and sensory deficits due to characteristic histopathological hallmarks such as neuroinflammation, demyelination and axonal and synaptic damages. In this scenario, neuropathic pain (NP) inflicts reduced quality of life to the patients. Pregabalin (PGB), an analogue of gabapentin, is well tolerated at low oral doses and is the first choice for treatment of NP. Dimethyl fumarate (DMF), in addition to its double effect on the disease (neuroprotection and immunomodulation), is an easily administered oral drug with few side effects. Therefore, the association of these drugs may be useful for both controlling the progression of the disease and reducing neuropathic pain. Objective: To study the effects of the association of Dimethyl fumarate (DMF) and Pregabalin (PGB) on neuropathic pain (NP) in a murine model of Multiple Sclerosis (EM), the Experimental Autoimmune Encephalomyelitis (EAE). Methods: 40 female C57BL6J mice will be divided into 5 groups: Naive (1), EAE + Vehicle (2), EAE + DMF (3), EAE + Pregabalin (4), EAE + DMF + Pregabalin (5). Pharmacological treatment will begin with the presentation of clinical signs and it will be maintained up to 28 days post-induction (dpi). Throughout the experimental period, all animals will be submitted to behavioral tests such as von-Frey and walking track test (Catwalk) in order to evaluate the efficacy of the drugs on clinical presentation and NP. The tissues will be evaluated for neuroinflammation, glial reactivity, demyelination and synaptic damage. (AU)