title: A diminished response to formalin stimulation reveals a role for the glutamate transporters in the altered pain sensitivity of mice with experimental autoimmune encephalomyelitis (EAE).
abstract: Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) in which neuropathic pain is now recognized as a major symptom. To date, few studies have examined the underlying mechanisms of neuropathic pain in MS. Recently we showed that in a chronic-relapsing animal model of MS, experimental autoimmune encephalomyelitis (EAE), characteristic neuropathic behaviours develop. However, responses to persistent noxious stimuli in EAE remain unexplored. We, therefore set out to characterize the changes in pain sensitivity in our EAE model to subcutaneous injection of formalin. We show here that female C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG(35-55)) display a significant decrease in elicited pain behaviours in response to formalin injection. These effects were found to involve dysregulation of the glutamatergic system in EAE. We show here that these effects are mediated by decreased glutamate transporter expression associated with EAE. Our findings demonstrate that dysregulation of glutamate transporter function in EAE mice is an important mechanism underlying the abnormal pain sensitivity in response to persistent noxious stimulation of mice with EAE and also sheds light on a potential mechanism underlying neuropathic pain behaviours in this model.
authors.affiliation: Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alta., Canada Centre for Neuroscience, University of Alberta, Edmonton, Alta., Canada Department of Chemistry, Columbia University, New York, NY, USA.
authors.forename: Camille Joanne
authors.initials: CJ
authors.lastname: Olechowski
authors.forename: Ambica
authors.initials: A
authors.lastname: Parmar
authors.forename: Brooke
authors.initials: B
authors.lastname: Miller
authors.forename: Jared
authors.initials: J
authors.lastname: Stephan
authors.forename: Gustavo
authors.initials: G
authors.lastname: Tenorio
authors.forename: Kristy
authors.initials: K
authors.lastname: Tran
authors.forename: James
authors.initials: J
authors.lastname: Leighton
authors.forename: Bradley James
authors.initials: BJ
authors.lastname: Kerr
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010146:Pain / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018094:Receptors, Metabotropic Glutamate; D005557:Formaldehyde; D018698:Glutamic Acid
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