title: Pain in experimental autoimmune encephalitis: a comparative study between different mouse models.
abstract: BACKGROUND
  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. 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Mice 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.
  
  
  CONCLUSIONS
  Diverse 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.
authors.affiliation: Pharmacology Institut, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, D-69120, Germany.
authors.forename: Jianning
authors.initials: J
authors.lastname: Lu
authors.forename: Martina
authors.initials: M
authors.lastname: Kurejova
authors.forename: Laura N
authors.initials: LN
authors.lastname: Wirotanseng
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
authors.forename: Anke
authors.initials: A
authors.lastname: Tappe-Theodor
mesh_terms: D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000150:complications*; D005106:Exploratory Behavior; D005260:Female; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D018991:Myelin Proteolipid Protein / Q000633:toxicity*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D010146:Pain / Q000209:etiology* / Q000473:pathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000633:toxicity*; D010525:Peripheral Nerves / Q000503:physiopathology
chemical_list: D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); C435023:myelin proteolipid protein (139-151); D005620:Freund's Adjuvant