Structural and functional changes in the thalamus, hypothalamus, and amygdala |
Hyperexcitability of the cell membrane of central neurons, decreased action potential threshold, increased synaptic strength, decreased descending inhibitory transmission, reduced activation threshold, and enlarged receptive fields |
Loss of gray matter volume in the anterior and posterior cingulate cortex and prefrontal cortex |
Heightened functional activity within the somatosensory cortex (sensory processing), insula (emotional context of sensation, sensory appraisal), and amygdala (mood processing) |
Increased temporal summation (leading to increasing ascending sensory amplification) and reduced conditioned pain modulation (reduction in descending inhibitory signals) |
Maladaptive central and peripheral neuroplasticity |
Hypothalamic-pituitary-adrenal axis changes |
Hyperactive sympathetic nervous system and endogenous opioid system |
Changes in neurotransmitter concentrations in the cerebrospinal fluid |
Adapted from information in reference 1.