title: Peripheral and Central Neuroinflammatory Changes and Pain Behaviors in an Animal Model of Multiple Sclerosis.
abstract: Pain is a widespread and debilitating symptom of multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. Although central neuroinflammation and demyelination have been implicated in MS-related pain, the contribution of peripheral and central mechanisms during different phases of the disease remains unclear. In this study, we used the animal model experimental autoimmune encephalomyelitis (EAE) to examine both stimulus-evoked and spontaneous pain behaviors, and neuroinflammatory changes, over the course of chronic disease. We found that mechanical allodynia of the hind paw preceded the onset of clinical EAE but was unmeasurable at clinical peak. This mechanical hypersensitivity coincided with increased microglial activation confined to the dorsal horn of the spinal cord. The development of facial mechanical allodynia also emerged in preclinical EAE, persisted at the clinical peak, and corresponded with pathology of the peripheral trigeminal afferent pathway. This included T cell infiltration, which arose prior to overt central lesion formation and specific damage to myelinated neurons during the clinical peak. Measurement of spontaneous pain using the mouse grimace scale, a facial expression-based coding system, showed increased facial grimacing in mice with EAE during clinical disease. This was associated with multiple peripheral and central neuroinflammatory changes including a decrease in myelinating oligodendrocytes, increased T cell infiltration, and macrophage/microglia and astrocyte activation. Overall, these findings suggest that different pathological mechanisms may underlie stimulus-evoked and spontaneous pain in EAE, and that these behaviors predominate in unique stages of the disease.
authors.affiliation: School of Medical Sciences, UNSW Medicine, The University of New South Wales (UNSW Australia) , Sydney, NSW , Australia.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Duffy
authors.affiliation: School of Medical Sciences, UNSW Medicine, The University of New South Wales (UNSW Australia) , Sydney, NSW , Australia.
authors.forename: Chamini J
authors.initials: CJ
authors.lastname: Perera
authors.affiliation: School of Medical Sciences, UNSW Medicine, The University of New South Wales (UNSW Australia) , Sydney, NSW , Australia.
authors.forename: Preet G S
authors.initials: PG
authors.lastname: Makker
authors.affiliation: School of Medical Sciences, UNSW Medicine, The University of New South Wales (UNSW Australia) , Sydney, NSW , Australia.
authors.forename: Justin G
authors.initials: JG
authors.lastname: Lees
authors.affiliation: School of Medical Sciences, UNSW Medicine, The University of New South Wales (UNSW Australia) , Sydney, NSW , Australia.
authors.forename: Pascal
authors.initials: P
authors.lastname: Carrive
authors.affiliation: School of Medical Sciences, UNSW Medicine, The University of New South Wales (UNSW Australia) , Sydney, NSW , Australia.
authors.forename: Gila
authors.initials: G
authors.lastname: Moalem-Taylor
keywords: T cells; experimental autoimmune encephalomyelitis; glia; multiple sclerosis; neuroinflammation; pain