Central nervous system plasticity associated with pain in a mouse model of multiple sclerosis, and the antinociceptive effects of the antidepressant phenelzine

• Author / Creator

  Potter, Liam E

• Multiple sclerosis (MS) is a chronic, progressive disease that involves neuroinflammation, demyelination, and neurodegeneration within the central nervous system (CNS). While loss of motor function and paralysis are considered the primary clinical consequences of MS, the disease is also associated with a variety of secondary symptoms. One of the most common and debilitating secondary symptoms of MS is pain. The underlying neurobiological mechanisms of pain in MS are poorly understood, and the currently available treatments are generally inadequate. Pain in MS can be studied using the inducible animal disease model experimental autoimmune encephalomyelitis (EAE). This thesis focuses on elucidating the cellular and circuit/systems-level mechanisms underlying pain in the MOG35-55/C57/BL6 murine EAE model. Altered neuronal function and structural/synaptic plasticity are characterized within the dorsal horn (DH) and the primary somatosensory cortex (S1) in early EAE, using a variety of optical imaging and immunohistochemical methods. We also assess the effects of treatment with the antidepressant phenelzine (PLZ) on neuronal plasticity and behavioral measures of pain in EAE, and in the formalin model of subacute chemogenic pain. PLZ, which acts to raise CNS levels of the monoamines (5-HT, NA, DA) and GABA, reduced nociceptive responses in the second phase of the formalin model, and reversed allodynia in EAE. PLZ also reversed or attenuated many of the plastic changes that we identified in the CNS in EAE, and acts to restore or augment inhibition in the DH/S1. These experiments identify novel forms of CNS plasticity associated with pain in EAE, and also identify a novel use for PLZ in mitigating this plasticity and treating pain. This work helps validate and advance the use of MOG35-55/C57/BL6 EAE as a model for pain in MS, and may also inform the development of novel pain treatments.

• Subjects / Keywords

  • Multiple sclerosis
  • Plasticity
  • Somatosensory cortex
  • S1
  • Dorsal horn
  • CNS
  • Phenelzine
  • EAE
  • Pain
  • Experimental autoimmune encephalomyelitis
  • MAOI

• Graduation date

  Fall 2017

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R32805F5J

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.