Learning Objective #1: Explain three pain-immune pathways that can be used to identify variables in pain research

Learning Objective #2: List five variables that affect neuroimmune indices and pain/functional outcomes among patients undergoing spine surgery

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Pain is the most common symptom that prompts medical attention accounting for over seventy million office visits per year. Over 90% of all diseases may be associated with pain. It is the second leading reason for work absenteeism with 65 million Americans suffering painful disabilities at any given time resulting in over 50 million lost workdays per year and an estimated three billion in lost wages. Research focusing on the pathophysiology, diagnosis and treatment of pain syndromes is essential for improving patient outcomes, including quality of life. The basis of psychoneuroimmunology lies in the bidirectional communication of the neurological and immune systems within the context of the psychological being. Local proinflammatory cytokine production parallels the production of peripheral cytokines in response to stress activation due to pain and injury. The hypothalamic-pituitary-adrenal (HPA) axis and locus coeruleus-norepinephrine (LC-NE) sympathetic systems are activated by perceived pain or other forms of stress, both sensory and cognitive (Melzack, 1999). Concurrently, when injury occurs, cytokines and cortisol are released into the bloodstream and are carried to the hypothalamus where they act directly on the HPA axis and LC-NE-sympathetic systems, the two major pillars of the stress system. The limbic system, which includes the hippocampus, is activated, affecting the emotional, motivational, homeostatic and cognitive responses to pain. From this paradigm, the linkages between pain, stress and mood disturbance (anxiety and depression) are convincingly interdependent and must be measured when considering the study of pain phenomena. Correlations between pain, stress, mood disturbance and proinflammatory cytokine production will be discussed.