Avaliação da crotalfina como perspectiva terapêutica da Encefalomielite Autoimune Experimental, um modelo animal de esclerose múltipla

Abstract

Multiple sclerosis (MS) is an inflammatory, autoimmune and demyelinating disease of the central nervous system (CNS), which has no cure and causes sensory and motor impairments. Cells of the immune system actively participate in the pathogenesis and progression of this disease by attacking the myelin sheath and inducing neuroinflammation, generating tissue damage, demyelination and neuronal death. Among several symptoms caused by MS, pain is present in most individuals. Crotalphine (CRO), a 14-aa synthetic peptide, induces analgesic activity by endogenous opioid release mediated by type 2 cannabinoid receptors activation. Studies demonstrated that the control of neuroinflammation through activation of type 2 cannabinoid receptors contributes to the control of the disease in an animal model of MS. Our aims were to assess the effects of CRO on MOG35–55-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS, evaluating the pain, progression of motor impairment and some neuroinflammatory parameters involved in this model. EAE decreased the nociceptive threshold, determined using an electronic pressure-meter test and induced clinical signs assessed through scores from 0 to 5. No changes were observed in BDNF, NGF and MBP expression in the spinal cord. CRO (50 μg/kg) was administered in a single dose (on the 5th day after immunization) or in 5 doses (starting on 12th day after immunization, one daily dose). Both protocols

of treatment decreased the severity of the clinical signs when compared to saline- treated animals, reduced the expression of IL-17 and reduced the immunoreactivity of

the neuronal activity, microglia/macrophages and astrocytes markers induced by EAE in spinal cord; when administered for 5 days, CRO decreased CD11b expression in spinal cord; single dose was able to caused partial reversion of EAE-induced mechanical hyperalgesia, reduced TNF-α expression and inflammatory infiltrate in spinal cord, reduced Th17 cells in the lymph nodes, and decreased myelin thickness in sciatic nerve observed in untreated group. These results may explain the improvement of the clinical signs and the attenuation of neuroinflammation induced by EAE, pointing out CRO as a promising agent for the control of MS.