Figure 2.

Schematic of intraganglionic mechanisms of craniofacial muscle pain. Nociceptive inputs from injured or inflamed craniofacial muscle produce extensive changes in gene expression in primary afferents and satellite glia within trigeminal ganglia. Reactive oxygen species (ROS) are increased, which may enhance genetic and functional changes. Primary afferents, satellite glia, and macrophages produce an array of cytokines and chemokines, such as tumor necrosis factor α (TNFα), interleukin 1β (IL1β), interleukin 6 (IL6), C-X3-C motif chemokine ligand 1 (CX3CL1; fractalkine), and granulocyte-macrophage colony-stimulating factor (GM-CSF). These factors sensitize injured afferents to enhance hyperalgesia (primary hyperalgesia). These sensitizing factors propagate into adjacent neurons from uninjured tissues, producing ectopic pain.