Inflammation in cold complex regional pain syndrome.

BACKGROUND: In patients with complex regional pain syndrome (CRPS), the temperature of the affected side often differs from that of the contralateral side. In the acute phase, the affected side is usually warmer than the contralateral side, the so-called 'warm' CRPS. This thermal asymmetry can develop into a colder affected side, the so-called 'cold' CRPS. In contrast to cold CRPS, in warm CRPS, inflammation is generally assumed to be present. However, there are reports of cold CRPS patients, successfully treated with vasodilatation therapy, who subsequently displayed warm CRPS. It seems that inflammation could be 'hidden' behind vasomotor disturbance. This study was designed to test this hypothesis. METHODS: A retrospective analysis was made of patients in our CRPS database. We defined three types of CRPS: cold CRPS, neither cold nor warm (intermediate) CRPS, and warm CRPS. Of these patients, the difference between the level of the pro-inflammatory cytokines interleukin (IL)-6 (Δ IL-6) and tumor necrosis factor (TNF)-α (Δ TNF-α) in the affected extremity and that in the contralateral extremity was determined. RESULTS: The bilateral difference of the level of these cytokines did not differ among patients with cold CRPS, intermediate CRPS, or those with warm CRPS. CONCLUSION: Inflammation may be involved in cold CRPS.

Diagnostic criteria in patients with complex regional pain syndrome assessed in an out-patient clinic.

BACKGROUND: Specific criteria have been described and accepted worldwide for diagnosing patients with complex regional pain syndrome (CRPS). Nevertheless, a clear-cut diagnosis cannot be confirmed in a number of cases. AIM: The objective of this study was to investigate the effectiveness of the described diagnostic criteria used by several clinical disciplines. METHODS: We included 195 patients who were referred to our pain clinic within a period of 1 year. Data were collected on patient characteristics, signs, symptoms, disease-related medication, and the background of the referring clinicians. RESULTS: The Harden and Bruehl criteria were confirmed in 95 patients (49%). These patients used a higher than average number of analgesics, opiates, and anti-oxidants, and frequently received prescriptions for benzodiazepines instead of anti-depressants. The mean disease duration was 29 +/- 4.6 months and the mean visual analogue score for pain was 8.1 +/- 0.19. A subgroup of patients had a colder temperature in the affected extremity compared with the unaffected extremity. This subgroup showed a longer disease duration and higher visual analogue scale pain. CONCLUSION: The diagnostic criteria used to determine CRPS should be further improved. A large number of referred patients experienced substantial pain, without receiving adequate medication. Disease-related medication is unrelated to CRPS-specific disease activity. Knowledge of underlying mechanisms is warranted before an adequate pharmaceutical intervention can be considered.

Increased plasma glutamate, glycine, and arginine levels in complex regional pain syndrome type 1.

BACKGROUND: Various inflammatory mediators have been identified as potential contributors to complex regional pain syndrome type 1 (CRPS1), but these mediators do not entirely explain certain manifestations of the syndrome, such as pain. The objective of this study was to investigate the role of amino acids in the pathogenesis of CRPS1. METHODS: We used HPLC to determine plasma concentrations of 16 amino acids, especially those related to the NMDA receptor (e.g., glutamate and glycine) and nitric oxide (NO) synthesis (e.g., arginine and citrulline) in patients with CRPS1 (n=64) and age- and sex-matched healthy controls (n=51). Patients rated pain intensity (visual analog scale) and the subjective experience of pain intensity (McGill Pain Questionnaire). Psychological dysfunction was assessed using the SCL-90. RESULTS: Relative to controls, in CRPS1 patients, plasma levels of glutamate, arginine, taurine, and glycine were increased, and plasma levels of glutamine and the ratio of citrulline to arginine were decreased. Remarkably, in CRPS1 patients there was a highly significant inverse correlation between glutamine and glutamate, although the sum of molar concentrations of glutamate and glutamine remains unchanged. Subjective measures of pain and indicators of psychoneuroticism and emotional instability did not correlate with amino acid levels. CONCLUSION: This study shows for the first time a pronounced increase in amino acid levels in this chronic pain syndrome. The marked differences in glutamate, glutamine, glycine, taurine and arginine levels between patients and controls suggest the involvement of both the NDMA receptor and the endothelium-dependent arginine-NO system in CRPS1.