P83: Central Neuropathic Pain Development in Experimental Autoimmune Encephalomyelitis C57BL/6 Mouse Model Induced by QS-21 Adjuvant

Central neuropathic pain (CNP) is considered as a complicated sensory disturbance which many multiple sclerosis (MS) patients suffer from. Although monophasic experimental autoimmune encephalomyelitis (EAE) mouse model is a gold standard model in preclinical research of MS, severe movement deficit could confound pain behaviors evaluation over the disease course. In this study, complete Freund&rsquo;s adjuvant (CFA) was substituted with an acylated triterpene glycoside saponin adjuvant named quillaja saponin-21 (QS-21) to establish EAE model for CNP development. Twentyfour, 5-7 weeks old female C57BL/6 mice were randomly divided into three groups. Two groups immunized with MOG35-55 peptide emulsified with CFA and QS-21 adjuvant. The last group received PBS as negative control group. Thermal hyperalgesia as a CNP clinical manifestation through hot plate test and clinical signs were assessed for 60 days' post immunization (p.i). On days 21 and 60 p.i mice were sacrificed and TCD4+, TCD8+, IL-17+ cells in total splenocytes population by flow cytometry and lymphocyte infiltration and demyelination of brain samples by histopathological staining were evaluated. EAE was established in MOG+QS-21 and MOG+CFA groups as mild relapsing-remitting and monophasic models, respectively. Thermal hyperalgesia developed in the bilateral hindpaws on the onset of clinical symptoms in MOG+CFA and MOG+QS-21 groups and it was maintained until study completion in MOG+QS-21 group. TCD4+, TCD8+ and IL-17+ cells population in MOG+QS-21 and MOG+CFA groups increased significantly (P<0.05) on days 21 and 60 p.i compared to PBS group. Although, inflammatory cells infiltration were increased significantly on days 21 and 60 in MOG+QS-21 and MOG+CFA groups, however demyelination was seen on days 21 and 60 only in MOG+CFA group compared to PBS group (P<0.05). QS-21 adjuvant is capable of establishing mild relapsing-remitting EAE model for CNP development with severe neuro-inflammation and no significant demyelination in white matter.