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Kevin C Thorburn, John W Paylor, Christine A Webber, Ian R Winship, Bradley J Kerr
Trigeminal neuropathic pain is a well-recognized complication of the demyelinating disease multiple sclerosis (MS). However, the mechanisms underlying MS-related trigeminal neuropathic pain are poorly understood. This can be attributed, at least in part, to the lack of an animal model that exhibits trigeminal pathology similar to that described in MS. Experimental autoimmune encephalomyelitis (EAE) is an animal model that is commonly used to study the pathophysiology of MS. We show here that mice with EAE exhibit increased sensitivity to air puffs applied to the whisker pad...
March 2016: Pain
David Henrique Rodrigues, Bruno Pereira Leles, Vivian Vasconcelos Costa, Aline Silva Miranda, Daniel Cisalpino, Dawidson Assis Gomes, Danielle Glória de Souza, Antônio Lúcio Teixeira
Pain is one of the main symptoms of multiple sclerosis, a demyelinating disease of the central nervous system that affects millions of people worldwide. The experimental autoimmune encephalomyelitis (EAE) is considered an experimental model of multiple sclerosis, and besides motor weakness, hypernociception is one of the clinical signs of animals with EAE. In this study, we investigated the influence of some cytokines in the generation of the hypernociceptive response in a mouse model of EAE using MOG35-55 ...
November 2016: Molecular Neurobiology
Melissa A Day, Dawn M Ehde, L Charles Ward, Narineh Hartoonian, Kevin N Alschuler, Aaron P Turner, George H Kraft, Mark P Jensen
OBJECTIVES: Pain is a significant problem for many individuals with multiple sclerosis (MS). Pain is often associated with other MS symptoms (eg, physical, sensorimotor, cognitive declines), and both pain and MS symptoms are hypothesized to contribute to psychosocial problems (eg, depression), other symptoms (eg, fatigue, sleep disturbance), and functional impairments (eg, pain interference). On the basis of a biopsychosocial model, we sought to: (1) examine the associations between pain, MS symptoms, depression, psychosocial, and functional variables and (2) identify possible risk and protective factors associated with pain in MS...
February 2016: Clinical Journal of Pain
Iman Fatemi, Ali Shamsizadeh, Fatemeh Ayoobi, Zahra Taghipour, Mohammad Hossein Sanati, Ali Roohbakhsh, Manijeh Motevalian
The aim of this study was to evaluate the effects of orexin-A (OX-A) on behavioral and pathological parameters and on gene expression of some multiple sclerosis-related peptides in a model of experimental autoimmune encephalomyelitis (EAE). EAE was induced by subcutaneous administration of MOG 35-55. Following immunization, the treatment was initiated by using SB.334867 (orexin-1 receptor antagonist) and/or OX-A. Locomotor activity and exploratory behaviors were monitored using open field and T-maze continuous alternation task (T-CAT) respectively...
February 15, 2016: Journal of Neuroimmunology
Margherita Brindisi, Samuele Maramai, Sandra Gemma, Simone Brogi, Alessandro Grillo, Lorenzo Di Cesare Mannelli, Emanuele Gabellieri, Stefania Lamponi, Simona Saponara, Beatrice Gorelli, Daniele Tedesco, Tommaso Bonfiglio, Christophe Landry, Kwang-Mook Jung, Andrea Armirotti, Livio Luongo, Alessia Ligresti, Fabiana Piscitelli, Carlo Bertucci, Marie-Pierre Dehouck, Giuseppe Campiani, Sabatino Maione, Carla Ghelardini, Anna Pittaluga, Daniele Piomelli, Vincenzo Di Marzo, Stefania Butini
We report the discovery of compound 4a, a potent β-lactam-based monoacylglycerol lipase (MGL) inhibitor characterized by an irreversible and stereoselective mechanism of action, high membrane permeability, high brain penetration evaluated using a human in vitro blood-brain barrier model, high selectivity in binding and affinity-based proteomic profiling assays, and low in vitro toxicity. Mode-of-action studies demonstrate that 4a, by blocking MGL, increases 2-arachidonoylglycerol and behaves as a cannabinoid (CB1/CB2) receptor indirect agonist...
March 24, 2016: Journal of Medicinal Chemistry
James C Watson, Paola Sandroni
Chronic pain is common in patients with neurologic complications of a central nervous system insult such as stroke. The pain is most commonly musculoskeletal or related to obligatory overuse of neurologically unaffected limbs. However, neuropathic pain can result directly from the central nervous system injury. Impaired sensory discrimination can make it challenging to differentiate central neuropathic pain from other pain types or spasticity. Central neuropathic pain may also begin months to years after the injury, further obscuring recognition of its association with a past neurologic injury...
March 2016: Mayo Clinic Proceedings
Mansoureh Togha, Nahid Abbasi Khoshsirat, Abdorreza Naser Moghadasi, Faezeh Mousavinia, Mohammad Mozafari, Mohamadreza Neishaboury, Seyed Mahmood Mousavi
BACKGROUND: Headaches are one of the most frequent reasons for pain in multiple sclerosis (MS) individuals. Characterization of headaches and delineating possible relationships with MS-related determinants can ultimately circumvent headaches. METHODS: In a prospective case-control study, 65 Iranian relapsing-remitting MS (RRMS) patients and 65 healthy controls were recruited during patients' admission for attack-period treatment and asked about characteristics and co-symptoms of headaches they experienced in the preceding week and usage of disease modifying drugs (DMDs) and types of MS attacks were also inquired...
January 5, 2016: Iranian Journal of Neurology
Peter M Grace, Lisa C Loram, John P Christianson, Keith A Strand, Johanna G Flyer-Adams, Kathryn R Penzkover, John R Forsayeth, Anne-Marie van Dam, Melissa J Mahoney, Steven F Maier, Raymond A Chavez, Linda R Watkins
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...
January 2017: Brain, Behavior, and Immunity
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