Plasma amino acids changes in complex regional pain syndrome.

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.

Establishing a relationship between bacteria in the human gut and complex regional pain syndrome.

Complex Regional Pain Syndrome (CRPS) is a serious and painful condition involving the peripheral and central nervous systems. Full comprehension of the disorder's pathophysiology remains incomplete, but research implicates the immune system as a contributor to chronic pain. Because of the impact gastrointestinal bacteria have in the development and behavior of the immune system, this study compares the GI microbial communities of 16 participants with CRPS (5 of whom have intestinal discomforts) and 16 healthy controls using 454 sequencing technology. CRPS subjects were found to have significantly less diversity than their healthy counterparts. Statistical analysis of the phylogenetic classifications revealed significantly increased levels of Proteobacteria and decreased levels of Firmicutes in CRPS subjects. Clustering analysis showed significant separation between healthy controls and CRPS subjects. These results support the hypothesis that the GI microbial communities of CRPS participants differ from those of their healthy counterparts. These variations may hold the key to understanding how CRPS develops and provide information that could yield a potential treatment.

Changes in plasma cytokines and their soluble receptors in complex regional pain syndrome.

UNLABELLED: Complex Regional Pain Syndrome (CRPS) is a chronic and often disabling pain disorder. There is evidence demonstrating that neurogenic inflammation and activation of the immune system play a significant role in the pathophysiology of CRPS. This study evaluated the plasma levels of cytokines, chemokines, and their soluble receptors in 148 subjects afflicted with CRPS and in 60 gender- and age-matched healthy controls. Significant changes in plasma cytokines, chemokines, and their soluble receptors were found in subjects with CRPS as compared with healthy controls. For most analytes, these changes resulted from a distinct subset of the CRPS subjects. When the plasma data from the CRPS subjects was subjected to cluster analysis, it revealed 2 clusters within the CRPS population. The category identified as most important for cluster separation by the clustering algorithm was TNFα. Cluster 1 consisted of 64% of CRPS subjects and demonstrated analyte values similar to the healthy control individuals. Cluster 2 consisted of 36% of the CRPS subjects and demonstrated significantly elevated levels of most analytes and in addition, it showed that the increased plasma analyte levels in this cluster were correlated with disease duration and severity. PERSPECTIVE: The identification of biomarkers that define disease subgroups can be of great value in the design of specific therapies and of great benefit to the design of clinical trials. It may also aid in advancing our understanding of the mechanisms involved in the pathophysiology of CRPS, which may lead to novel treatments for this very severe condition.

Changes in immune and glial markers in the CSF of patients with Complex Regional Pain Syndrome.

Complex Regional Pain Syndrome is a severe chronic pain condition characterized by sensory, autonomic, motor and dystrophic signs and symptoms. The pain in CRPS is continuous, it worsens over time, and it is usually disproportionate to the severity and duration of the inciting event. This study compares cerebrospinal fluid (CSF) levels of pro- and anti-inflammatory cytokines, chemokines and several biochemical factors (glial fibrillary acidic protein (GFAP), the nitric oxide metabolites (nitrate plus nitrite), the excitatory amino acid neurotransmitter glutamate, calcium, total protein and glucose) in patients afflicted with CRPS to levels found in patients suffering with other non-painful or painful conditions. The aim of the study is to determine the degree of involvement of glial cells and immune system mediators in the pathophysiology of CRPS. There was no elevation or reduction of a CSF marker that was specific for CRPS patients. However, there were several patterns of markers that could be helpful in both elucidating the mechanisms involved in the disease process and supporting the diagnosis of CRPS. The most common pattern was found in 50% (11 out of 22) of the CRPS patients and consisted of; elevated IL-6, low levels of IL-4 or IL-10, increased GFAP or MCP1 and increases in at least two of the following markers NO metabolites, calcium or glutamate. The results from this and other similar studies may aid in elucidating the mechanisms involved in the pathophysiology of CRPS. A better understanding of these mechanisms may lead to novel treatments for this very severe, life-altering illness.

Changes in cerebrospinal fluid levels of pro-inflammatory cytokines in CRPS.

Complex Regional Pain Syndrome (CRPS) Types I and II are characterized by various combinations of sensory, autonomic and motor abnormalities. Pain disproportionate to the severity and duration of the inciting event is the most devastating symptom. In animal studies, conditions resulting in exaggerated pain states demonstrate elevated pro-inflammatory cytokines. In addition, pro-inflammatory cytokines have been shown to induce or increase neuropathic and inflammatory pain. Utilizing high sensitivity enzyme linked immunosorbent assay (ELISA), we compared the levels of the pro-inflammatory cytokines interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha) in the cerebrospinal fluid (CSF) of patients afflicted with CRPS to CSF levels found in other patients with and without painful conditions. The results from this study demonstrated significant increases in IL-1beta and IL-6, but not TNF-alpha in the CSF of individuals afflicted with CRPS as compared to controls. CSF cytokine levels in controls with painful conditions did not differ from levels in controls without pain. These increases showed no correlation with the patient's gender or weight. These results are consistent with studies that suggest that the pathogenesis of CRPS is due in part to central neuroimmune activation.