Understanding the spectrum of non-motor symptoms in multiple sclerosis: insights from animal models

Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic, physically debilitating neurological disorder. In addition to experiencing motor disability, patients with multiple sclerosis also experience a variety of non-motor symptoms, including cognitive deficits, anxiety, depression, sensory impairments, and pain. However, the pathogenesis and treatment of such non-motor symptoms in multiple sclerosis are still under research. Preclinical studies for multiple sclerosis benefit from the use of disease-appropriate animal models, including experimental autoimmune encephalomyelitis. Prior to understanding the pathophysiology and developing treatments for non-motor symptoms, it is critical to characterize the animal model in terms of its ability to replicate certain non-motor features of multiple sclerosis. As such, no single animal model can mimic the entire spectrum of symptoms. This review focuses on the non-motor symptoms that have been investigated in animal models of multiple sclerosis as well as possible underlying mechanisms. Further, we highlighted gaps in the literature to explain the non-motor aspects of multiple sclerosis in experimental animal models, which will serve as the basis for future studies.