Figure 1: Sympathetic-immune communication relevant to rheumatoid arthritis. Neural circuits for sympathetic regulation of immune functions in secondary lymphoid organs and tissue immunity (e.g., synovial tissue in an articulating joint). The brain receives immune system information in the form of circulating cytokines and chemokines, and from activated sensory neurons. The hypothalamus responds by sending the appropriate signals to areas of the brainstem that regulate the firing rates of sympathetic neurons (not shown). Neuron in these brainstem areas send their axons to the preganglionic sympathetic neurons located in the intermediolateral cell column of the thoracic and lumbar spinal cord. These sympathetic neurons are the first neuron of a two neuron chain. Preganglionic neurons send their axons to post-ganglionic neurons located in sympathetic ganglia. Axons of post-ganglionic neurons extend into the parenchyma of secondary lymphoid tissues (spleen and lymph nodes) to regulate immune functions. The SNS also sends postganglionic nerves to most organs and tissues of the body to modulate their essential functions, as well as, to regulate inflammatory and cell-mediated immune responses that may occur in each of these tissues due to infection or tissue damage. Of relevance to RA, the synovial tissue of articulating joints is innervated by sympathetic nerves, and is thought to play a role in inflammatory arthritis.