Targeting Amino Acid and Biogenic Amine Neurotransmitters to Improve Functional Outcomes in EAE

Multiple sclerosis (MS) affects an estimated 55,000-75,000 Canadians. While the primary symptoms of MS are losses of sensory and motor function, it is now recognized that chronic pain is also a major concern affecting up to 60% of these patients 1. Of the different pain syndromes seen in MS patients, neuropathic pain, which arises due to dysfunction in the nervous system as a result of the disease, is especially prevalent 2. Neuropathic pain is particularly distressing for these patients because conventional analgesic therapies are largely ineffective. Unfortunately, the development of new treatments for neuropathic pain in MS has been hampered by a lack of studies examining its underlying causes in the disease. The PI’s research program is among the first to examine the cellular mechanisms of neuropathic pain in an animal model commonly used to study MS, experimental autoimmune encephalomyelitis (EAE). EAE exhibits many of the same pathological features as MS and the PI has recently published one of the first studies to characterize the changes in pain sensitivity exhibited by mice in this model 3. Recent data from Dr. Kerr’s laboratory now indicates that there are significant changes in the levels of several key neurotransmitters/neuromodulators in the spinal cords of EAE mice that could mediate these changes 4. We have found an increased levels of the excitatory amino acid D-serine and a decreased levels of the inhibitory amino acid neurotransmitter ã-aminobutyric acid (GABA) along with reductions in the levels of the biogenic amines serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE).