Complex regional pain syndrome (CRPS) is a severe chronic pain condition that most often develops following trauma. Blood samples were collected from 220 individuals, 160 CRPS subjects, and 60 healthy pain-free controls. Plasma amino acid levels were compared and contrasted between groups. L-Aspartate, L-glutamate, and L-ornithine were significantly increased, whereas L-tryptophan and L-arginine were significantly decreased in CRPS subjects as compared to controls. In addition, the L-kynurenine to L-tryptophan ratio demonstrated a significant increase, whereas the global arginine bioavailability ratio (GABR) was significantly decreased in the CRPS subjects. The CRPS subjects demonstrated a significant correlation between overall pain and the plasma levels of L-glutamate and the L-kynurenine to L-tryptophan ratio. CRPS subjects also showed a correlation between the decrease in plasma L-tryptophan and disease duration. This study shows that CRPS subjects exhibit significant changes in plasma levels of amino acids involved in glutamate receptor activation and in amino acids associated with immune function as compared to healthy pain-free controls. A better understanding of the role plasma amino acids play in the pathophysiology of CRPS may lead to novel treatments for this crippling condition. 1. Introduction Complex regional pain syndrome (CRPS), formerly reflex sympathetic dystrophy (RSD) or causalgia, is a severe chronic neuropathic pain condition [1, 2]. CRPS usually develops following trauma and is thought to involve both central and peripheral components of the neuraxis [1, 3]. The signs and symptoms of CRPS cluster into four distinct subgroups: (1) abnormalities in pain processing, (2) skin color and temperature changes, (3) edema, vasomotor, and sudomotor abnormalities, and (4) motor dysfunction and trophic changes [4]. Continuous pain is the most devastating of these symptoms and has been reported to spread and worsen over time, and it is usually disproportionate to the severity and duration of the inciting event [2]. CRPS may result from 5% of all nerve injuries [5, 6] and affects between 200,000 and 1.2 million Americans. In our pain clinic, CRPS demonstrates a 4？:？1 female to male preponderance and an average age of onset of 37 years old [3]. The incidence of CRPS reported 3 months following radial fractures (28%) is significantly higher than the incidence (7%) reported 1 year after the same fracture [7]. The majority of CRPS patients undergo resolution of their symptoms, often spontaneously, and in only a minority of patients does the disease
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