Figure 4.

A schematic diagram representing the interaction between muscle, macrophages, and nociceptors in the peripheral nervous system. Macrophages, found in local tissue, can be polarized to and M1 phenotype that releases pro-inflammatory cytokines which activate nociceptors, or an M2 phenotype that releases anti-inflammatory cytokines which inhibit nociceptors. Our data support that there are greater M1 macrophages at the site of insult or injury in the sedentary state and that regular physical activity increases the proportion of M2 macrophages. Our data further support the notion that regular physical activity changes the state of the immune system so that there is a greater proportion of M2 macrophages and greater anti-inflammatory cytokine that mediate the analgesia of regular physical activity.