Behavioral assessment of neuropathic pain, fatigue, and anxiety in experimental autoimmune encephalomyelitis (EAE) and attenuation by interleukin-10 gene therapy

Autor: Steven F. Maier, Melissa J. Mahoney, Anne Marie van Dam, Peter M. Grace, John P. Christianson, Linda R. Watkins, Kathryn R. Penzkover, Raymond A. Chavez, Johanna G. Flyer-Adams, Keith A. Strand, John Forsayeth, Lisa C. Loram
Přispěvatelé: Anatomy and neurosciences, Amsterdam Neuroscience - Neuroinfection & -inflammation
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Anxiety
Neurodegenerative
Behavioral Neuroscience
0302 clinical medicine
Neuroinflammation
Psychology
Encephalomyelitis
Injections
Spinal
Fatigue
Behavior
Animal
biology
Experimental autoimmune encephalomyelitis
Pain Research
Interleukin-10
Hyperalgesia
Neuropathic pain
Neurological
medicine.symptom
Chronic Pain
Development of treatments and therapeutic interventions
Encephalomyelitis
Autoimmune
Experimental
Multiple Sclerosis
Spinal
Immunology
Motor Activity
Autoimmune Disease
Article
Myelin oligodendrocyte glycoprotein
Injections
03 medical and health sciences
Experimental
Life Expectancy
Behavioral and Social Science
medicine
Animals
Interpersonal Relations
Peripheral Neuropathy
Behavior
Neurology & Neurosurgery
5.2 Cellular and gene therapies
Endocrine and Autonomic Systems
Animal
Multiple sclerosis
Neurosciences
Genetic Therapy
medicine.disease
Rats
Dark agouti
Brain Disorders
030104 developmental biology
Good Health and Well Being
Mood disorders
biology.protein
Exploratory Behavior
Neuralgia
Motor Deficit
030217 neurology & neurosurgery
Autoimmune
Zdroj: Grace, P M, Loram, L C, Christianson, J P, Strand, K A, Flyer-Adams, J G, Penzkover, K R, Forsayeth, J R, van Dam, A M, Mahoney, M J, Maier, S F, Chavez, R A & Watkins, L R 2017, ' Behavioral assessment of neuropathic pain, fatigue, and anxiety in experimental autoimmune encephalomyelitis (EAE) and attenuation by interleukin-10 gene therapy ', Brain, Behavior, and Immunity, vol. 59, pp. 49-54 . https://doi.org/10.1016/j.bbi.2016.05.012
Brain, Behavior, and Immunity, 59, 49-54. Academic Press Inc.
ISSN: 0889-1591
Popis: Relapsing-remitting multiple sclerosis is commonly associated with motor impairments, neuropathic pain, fatigue, mood disorders, and decreased life expectancy. However, preclinical pharmacological studies predominantly rely on clinical scoring of motor deficit as the sole behavioral endpoint. Thus, the translational potential of these studies is limited. Here, we have assessed the therapeutic potential of a novel anti-inflammatory interleukin-10 (IL-10) non-viral gene therapy formulation (XT-101-R) in a rat relapsing remitting experimental autoimmune encephalomyelitis (EAE) model. EAE induced motor deficits and neuropathic pain as reflected by induction of low-threshold mechanical allodynia, suppressed voluntary wheel running, decreased social exploration, and was associated with markedly enhanced mortality. We also noted that voluntary wheel running was depressed prior to the onset of motor deficit, and may therefore serve as a predictor of clinical symptoms onset. XT-101-R was intrathecally dosed only once at the onset of motor deficits, and attenuated each of the EAE-induced symptoms and improved survival, relative to vehicle control. This is the first pharmacological assessment of such a broad range of EAE symptoms, and provides support for IL-10 gene therapy as a clinical strategy for the treatment of multiple sclerosis.
Databáze: OpenAIRE
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