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Sex Differences in Central Nervous System Plasticity and Pain in Experimental Autoimmune Encephalomyelitis

  • Author / Creator
    Catuneanu, Ana
  • Multiple sclerosis (MS) is a neurodegenerative autoimmune disease with many known structural and functional changes in the central nervous system (CNS). A well-recognized, but poorly understood, complication of MS is chronic pain. Little is known regarding the influence of sex on the development and maintenance of MS-related pain. This is important to consider, as MS is a predominantly female disease. Using the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, sex differences in measures of spinal cord inflammation and plasticity that accompany tactile hypersensitivity were explored. At disease onset (indicated by partial tail paralysis), behaviours indicative of nociception were assessed using von Frey monofilaments and the acetone test. Both male and female EAE mice demonstrated increased frequency and duration of pain behaviours, however this response was often lateralized in females. Spinal cord tissue was extracted on day of disease onset and prepared for Golgi-Cox and immunohistochemical staining to visualize features of lamina 4-5 within the dorsal horn, where pain information is processed, integrated and relayed by wide dynamic range (WDR) neurons. While substantial inflammatory activity was observed in both sexes, only male EAE mice exhibit robust staining of axonal injury markers and increased dendritic arbourization in morphology of deep dorsal horn neurons. These findings suggest tactile hypersensitivity in male mice with EAE may rely more heavily on neurodegenerative and plasticity-related mechanisms compared to female EAE mice, in addition to the immune system dysregulation prominent in both sexes. Furthermore, dendritic spine density analysis revealed deep dorsal horn neurons from male EAE mice showing pain behaviours are significantly less complex, whereas the opposite was seen from EAE males lacking pain responses. Morphological and inflammatory differences in the spinal cord associated with pain early in EAE progression supports the idea of differentially regulated pain pathways between the sexes. Results from this study may indicate future sex-specific targets that are worth investigating for their functional role in pain circuitry.

  • Subjects / Keywords
  • Graduation date
    Spring 2019
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-phgt-wn33
  • License
    Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.