We are establishing the mechanisms by which Sphingosine-1-Phosphate and its cognate receptors can impact intrinsic and synaptic mechanisms within molecularly-defined CeA neuron subpopulations that integrate the discriminative and emotional components of chronic pain. Our studies have the potential to show that S1PR1 activation of these neurons, perhaps with an immunomodulatory (not immunotoxic) drug that is already FDA-approved (fingolimod), can rapidly translate to the clinical treatment of chronic pain.