The pain of being sick: Implications of immune-to-brain communication for understanding pain

This review focuses on the powerful pain facilitatory effects produced by t he immune system. Immune cells, activated in response to infection, inflamm ation, or trauma, release proteins called proinflammatory cytokines. These proinflammatory cytokines signal the central nervous system, thereby creati ng exaggerated pain as well as an entire constellation of physiological, be havioral, and hormonal changes. These changes are collectively referred to as the sickness response. Release of proinflammatory cytokines by immune ce lls in the body leads, in turn, to release of proinflammatory cytokines by glia within the brain and spinal cord. Evidence is reviewed supporting the idea that proinflammatory cytokines exert powerful pain facilitatory effect s following their release in the body, in the brain, and in the spinal cord . Such exaggerated pain states naturally occur in situations involving infe ction, inflammation, or trauma of the skin, of peripheral nerves, and of th e central nervous system itself. Implications for human pain conditions are discussed.