myelin-oligodendrocyte-glycoprotein-(35-55) and acetovanillone

Central neuropathic pain is a common untreated symptom in progressive multiple sclerosis (PMS) and is associated with poor quality of life and interference with patients' daily activities. The neuroinflammation process and mitochondrial dysfunction in the PMS lesions generate reactive species. The transient potential receptor ankyrin 1 (TRPA1) has been identified as one of the major mechanisms that contribute to neuropathic pain signaling and can be activated by reactive compounds. Thus, the goal of our study was to evaluate the role of spinal TRPA1 in the central neuropathic pain observed in a PMS model in mice. We used C57BL/6 female mice (20-30 g), and the PMS model was induced by the experimental autoimmune encephalomyelitis (EAE) using mouse myelin oligodendrocyte glycoprotein (MOG

Topics: Acetanilides; Acetophenones; Analgesics; Animals; Antipyrine; Dipyrone; Encephalomyelitis, Autoimmune, Experimental; Female; Hyperalgesia; Mice; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; NADPH Oxidases; Nerve Tissue Proteins; Neuralgia; Nociception; Oligonucleotides, Antisense; Oxidative Stress; Oximes; Peptide Fragments; Pregabalin; Purines; Spinal Cord; Thioctic Acid; TRPA1 Cation Channel; Up-Regulation

To evaluate the role of NADPH oxidase-mediated reactive oxygen species (ROS) production in multiple sclerosis pathogenesis, we examined the effects of apocynin, an NADPH oxidase assembly inhibitor, on experimental autoimmune encephalomyelitis (EAE).. EAE was induced by immunization with myelin oligodendrocyte glycoprotein (MOG (35-55)) in C57BL/6 female mice. Three weeks after initial immunization, the mice were analyzed for demyelination, immune cell infiltration, and ROS production. Apocynin (30 mg/kg) was given orally once daily for the entire experimental course or after the typical onset of clinical symptom (15 days after first MOG injection).. Clinical signs of EAE first appeared on day 11 and reached a peak level on day 19 after the initial immunization. The daily clinical symptoms of EAE mice were profoundly reduced by apocynin. The apocynin-mediated inhibition of the clinical course of EAE was accompanied by suppression of demyelination, reduced infiltration by encephalitogenic immune cells including CD4, CD8, CD20, and F4/80-positive cells. Apocynin reduced MOG-induced pro-inflammatory cytokines in cultured microglia. Apocynin also remarkably inhibited EAE-associated ROS production and blood-brain barrier (BBB) disruption. Furthermore, the present study found that post-treatment with apocynin also reduced the clinical course of EAE and spinal cord demyelination.. These results demonstrate that apocynin inhibits the clinical features and neuropathological changes associated with EAE. Therefore, the present study suggests that inhibition of NADPH oxidase activation by apocynin may have a high therapeutic potential for treatment of multiple sclerosis pathogenesis.

Topics: Acetophenones; Animals; Animals, Newborn; Blood-Testis Barrier; Brain; Cells, Cultured; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Enzyme Inhibitors; Female; Leukoencephalopathies; Male; Mice; Mice, Inbred C57BL; Myelin-Oligodendrocyte Glycoprotein; NADPH Oxidases; Peptide Fragments; Reactive Oxygen Species; Severity of Illness Index; Spinal Cord