Fig. 5: Due to the dysregulation of the HPA axis there is a decrease in cortisol concentrations and an increase epinephrine (EPI) and NE production, the inhibition of immune cells is discontinued, and production of proinflammatory cytokines and glutamate is upregulated.

Consequently, this results in the manifestation of chronic pain states, and ultimately, chronic pain itself becomes a stressor, resulting in a perpetuated and dysregulated HPA axis response. Figure was created with BioRender.com.