Involvement of the sympathetic nervous system in complex regional pain syndrome

Complex regional pain syndrome (CRPS) occasionally develops as a complication of limb trauma. Sympathetic neurotransmitter release is compromised in the affected limb of at least a subgroup of patients throughout the course of the disorder, whereas signs of sympathetic deficit (a warm flushed limb) often evolve into signs of sympathetic overactivity (a cool moist limb) due to the development of adrenergic supersensitivity. Cross-talk between sympathetic neurotransmitters and the sensory neurons that signal pain appears to contribute to CRPS in a subgroup of patients. In addition, sympathetic activity may retard normal healing by aggravating the vascular disturbances associated with inflammation. Sympathetic dysfunction seems to originate from within the central nervous system in patients without peripheral nerve injury, possibly in association with chronic activation of the "defeat" response associated with inhibitory opioid-mediated pain modulation. Fatigue of this inhibitory process may unmask a facilitatory influence of arousal on nociceptive transmission in the thalamus and cortex that contributes to stress-induced pain.