Figure 3.

Non-pharmaceutical interventions restore proper signaling within the HPA axis and between higher structures. Exercise increases dendritic complexity and BDNF expression in the hippocampus, which restores negative input onto the hypothalamus to restore proper HPA axis output (1). Decreased CRF release stabilizes MC activation and infiltration associated with chronic pain disorders (2), thereby reducing peripheral nociceptive input. Exercise influences the descending pain pathway, likely through release of endogenous opioids, increasing neuronal activity, and balancing excitatory and inhibitory transmission (3). Cognitive behavioral therapy (CBT) alters the intrinsic functional connectivity (iFC) between brain regions associated with pain management, including connections between the prefontal cortex (PFC) and amygdala and somatosensory cortex and the basal ganglia network (BGN) (4). Cortical and hippocampal gray matter densities are also increased in patients following CBT (5).