title: Voluntary wheel running delays disease onset and reduces pain hypersensitivity in early experimental autoimmune encephalomyelitis (EAE).
abstract: Multiple sclerosis (MS) is classically defined by motor deficits, but it is also associated with the secondary symptoms of pain, depression, and anxiety. Up to this point modifying these secondary symptoms has been difficult. There is evidence that both MS and the animal model experimental autoimmune encephalomyelitis (EAE), commonly used to study the pathophysiology of the disease, can be modulated by exercise. To examine whether limited voluntary wheel running could modulate EAE disease progression and the co-morbid symptoms of pain, mice with EAE were allowed access to running wheels for 1h every day. Allowing only 1h every day of voluntary running led to a significant delay in the onset of clinical signs of the disease. The development of mechanical allodynia was assessed using Von Frey hairs and indicated that wheel running had a modest positive effect on the pain hypersensitivity associated with EAE. These behavioral changes were associated with reduced numbers of cFOS and phosphorylated NR1 positive cells in the dorsal horn of the spinal cord compared to no-run EAE controls. In addition, within the dorsal horn, voluntary wheel running reduced the number of infiltrating CD3(+) T-cells and reduced the overall levels of Iba1 immunoreactivity. Using high performance liquid chromatography (HPLC), we observed that wheel-running lead to significant changes in the spinal cord levels of the antioxidant glutathione. Oxidative stress has separately been shown to contribute to EAE disease progression and neuropathic pain. Together these results indicate that in mice with EAE, voluntary motor activity can delay the onset of clinical signs and reduce pain symptoms associated with the disease.
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada.
authors.forename: Curtis
authors.initials: C
authors.lastname: Benson
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Paylor
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Tenorio
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Winship
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Psychiatry, University of Alberta, Edmonton, AB T6G 2B7, Canada.
authors.forename: Glen
authors.initials: G
authors.lastname: Baker
authors.affiliation: Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Pharmacology, University of Alberta, Edmonton, AB T6E 2H7, Canada; Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada. Electronic address: bradley.kerr@ualberta.ca.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Kerr
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D006930:Hyperalgesia / Q000503:physiopathology / Q000534:rehabilitation; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000209:etiology* / Q000534:rehabilitation*; D009444:Neuritis, Autoimmune, Experimental / Q000139:chemically induced / Q000150:complications* / Q000534:rehabilitation; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017288:Pain Threshold / Q000502:physiology*; D010446:Peptide Fragments / Q000633:toxicity; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012420:Running / Q000502:physiology*; D018709:Statistics, Nonparametric
chemical_list: C491049:Aif1 protein, mouse; D015703:Antigens, CD; D002135:Calcium-Binding Proteins; C121673:Gprin1 protein, mouse; D008840:Microfilament Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; C445081:myelin oligodendrocyte glycoprotein (35-55); D052247:Nitric Oxide Synthase Type II; D003576:Electron Transport Complex IV
keywords: Exercise; GABA; Glutamate; Oxidative stress; Pain