Pain in experimental autoimmune encephalitis: a comparative study between different mouse models

Jianning Lu,Laura N Wirotanseng,Ralf A Linker,Rohini Kuner,Martina Kurejova,Anke Tappe-Theodor

doi:10.1186/1742-2094-9-233

Abstract

BackgroundPain can be one of the most severe symptoms associated with multiple sclerosis (MS) and develops with varying levels and time courses. MS-related pain is difficult to treat, since very little is known about the mechanisms underlying its development. Animal models of experimental autoimmune encephalomyelitis (EAE) mimic many aspects of MS and are well-suited to study underlying pathophysiological mechanisms. Yet, to date very little is known about the sensory abnormalities in different EAE models. We therefore aimed to thoroughly characterize pain behavior of the hindpaw in SJL and C57BL/6 mice immunized with PLP139-151 peptide or MOG35-55 peptide respectively. Moreover, we studied the activity of pain-related molecules and plasticity-related genes in the spinal cord and investigated functional changes in the peripheral nerves using electrophysiology.MethodsWe analyzed thermal and mechanical sensitivity of the hindpaw in both EAE models during the whole disease course. Qualitative and quantitative immunohistochemical analysis of pain-related molecules and plasticity-related genes was performed on spinal cord sections at different timepoints during the disease course. Moreover, we investigated functional changes in the peripheral nerves using electrophysiology.ResultsMice in both EAE models developed thermal hyperalgesia during the chronic phase of the disease. However, whereas SJL mice developed marked mechanical allodynia over the chronic phase of the disease, C57BL/6 mice developed only minor mechanical allodynia over the onset and peak phase of the disease. Interestingly, the magnitude of glial changes in the spinal cord was stronger in SJL mice than in C57BL/6 mice and their time course matched the temporal profile of mechanical hypersensitivity.ConclusionsDiverse EAE models bearing genetic, clinical and histopathological heterogeneity, show different profiles of sensory and pathological changes and thereby enable studying the mechanistic basis and the diversity of changes in pain perception that are associated with distinct types of MS.

Highlights

Pain can be one of the most severe symptoms associated with multiple sclerosis (MS) and develops with varying levels and time courses
SJL-EAE mice displayed the first signs of disease onset with tail weakness on day 10 and reached a peak in motor deficit functions at day 12 (Figure 1A), whereas C57-EAE mice showed the first symptoms at day 11 and a maximal disease score at day 17 (Figure 1B)
We found that SJL mice immunized with PLP139-151 peptide and C57 mice immunized with MOG35-55 peptide clearly showed thermal hyperalgesia, whereas only SJL-EAE mice developed marked mechanical allodynia in the chronic phase of the disease

Summary

Introduction

Pain can be one of the most severe symptoms associated with multiple sclerosis (MS) and develops with varying levels and time courses. MS-related pain is difficult to treat, since very little is known about the mechanisms underlying its development. Multiple sclerosis (MS) is one of the most common neurological diseases mostly affecting young adults. It is an incurable, chronic inflammatory, progressive neuroinflammatory and neurodegenerative disease with a still unclear etiology. Many studies are based on questionnaires and the reports on pain prevalence in MS patients remains difficult.

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