Influence of routine exercise on the peripheral immune system to prevent and alleviate pain

Routine physical activity reduces the onset of pain and exercise is a first line treatment for individuals who develop chronic pain. In both preclinical and clinical research regular exercise (routine exercise sessions) produces pain relief through multiple mechanisms such as alterations in the central and peripheral nervous system. More recently, it has been appreciated that exercise can also alter the peripheral immune system to prevent or reduce pain. In animal models, exercise can alter the immune system at the site of injury or pain model induction, in the dorsal root ganglia, and systemically throughout the body to produce analgesia. Most notably exercise shows the ability to dampen the presence of pro-inflammatory immune cells and cytokines at these locations. Exercise decreases M1 macrophages and the cytokines IL-6, IL-1β, and TFNα, while increasing M2 macrophages and the cytokines IL-10, IL-4, and IL-1ra. In clinical research, a single bout of exercise produces an acute inflammatory response, however repeated training can lead to an anti-inflammatory immune profile leading to symptom relief. Despite the clinical and immune benefits of routine exercise, the direct effect of exercise on immune function in clinical pain populations remains unexplored. This review will discuss in more detail the preclinical and clinical research which demonstrates the numerous ways through which multiple types of exercise alter the peripheral immune system. This review closes with the clinical implications of these findings along with suggestions for future research directions.