Complex regional pain syndrome: becoming more or less complex?

Complex regional pain syndrome (CRPS) is the newest name for the confusing conditions of reflex sympathetic dystrophy and causalgia. The epidemiology and the signs and symptoms of these conditions are discussed. Although much is only poorly understood about the aetiology of CRPS, the roles of neuropathic pain, prolonged inflammation and psychological factors are becoming clearer. Physical therapies remain the lynchpin of management but the roles of anti-inflammatory medication, sympathectomies and a team approach are emphasized.     

What is a meaningful pain reduction in patients with complex regional pain syndrome type 1?

OBJECTIVE: To investigate the degree of pain reduction in patients with complex regional pain syndrome type 1 (CRPS 1) that can be defined as "successful." DESIGN: All patients rated their pain on a visual analog scale (VAS; 0-10) before treatment and on three occasions after treatment, at 6 months, 1 year, and 2 years. Patients also rated a Global Perceived Effect (GPE) for their pain relief at the same time periods. The GPE items were classified as "successful" or "unsuccessful." The mean absolute and relative pain reduction (using the VAS) was calculated for both "successful" and "unsuccessful" GPE classifications for each time period. Sensitivity and specificity analyses were performed. PATIENTS: Sixty-one patients with CRPS 1. RESULTS: The patients defined a relative pain reduction of 58% (SD, 23.4) or more as "successful," whereas in "successful" and "unsuccessful" patient groups the pain was reduced significantly on the VAS. Furthermore, sensitivity and specificity analyses showed that a cut-off point of 50% relative pain reduction and a 3-cm absolute pain reduction on the VAS have the highest likelihood that patients will report their treatment "successful" on the GPE. CONCLUSIONS: Relative pain reduction of 50% or more and an absolute pain reduction of at least 3 cm on the VAS are accurate in predicting a successful pain reduction after a given treatment.     

Osteoprotegerin: A new biomarker for impaired bone metabolism in complex regional pain syndrome?

Osteoprotegerin (OPG) is important for bone remodeling and may contribute to complex regional pain syndrome (CRPS) pathophysiology. We aimed to assess the value of OPG as a biomarker for CRPS and a possible correlation with radiotracer uptake in 3-phase bone scintigraphy (TPBS). OPG levels were analyzed in 23 CRPS patients (17 women; mean age 50 ± 9.0 years; disease duration: 12 weeks [IQR 8–24]), 10 controls (6 women; mean age 58 ± 9.6 years) and 21 patients after uncomplicated fractures (12 women; mean age: 43 ± 15 years; time after fracture: 15 weeks [IQR: 6–22]). The CRPS and control patients also underwent TPBS. OPG in CRPS patients was significantly increased by comparison with both control groups (P = 0.001; Kruskal-Wallis test; CRPS patients: 74.1 pg/mL [IQR: 47.1–100.7]; controls: 46.7 pg/mL [IQR: 35.5–55.0]; P = 0.004; fracture patients: 45.9 pg/mL [IQR: 37.5–56.7]; P = 0.001). As a diagnostic test for CRPS, OPG had a sensitivity of 0.74, specificity of 0.80, positive predictive value of 68% and negative predictive value of 84%. Receiver operating characteristic curve analysis showed an area under the curve of 0.80 (CI: 0.68–0.91). For the CRPS-affected hand, a significant correlation between OPG and TPBS region of interest analysis in phase III was detected (carpal bones; r = 0.391; P = 0.03). The persistent OPG increase in CRPS indicates enhanced osteoblastic activity shown by increased radiotracer uptake in TPBS phase III. A contribution of bone turnover to CRPS pathophysiology is likely. OPG might be useful as a biomarker for CRPS.     

Clinical expression profiles of complex regional pain syndrome, fibromyalgia and a-specific repetitive strain injury: more common denominators than pain?

Purpose. To systematically evaluate and compare the clinical manifestations, disease course, risk factors and demographic characteristics of Complex Regional Pain Syndrome type 1 (CRPS), fibromyalgia (FM) and a-specific Repetitive Strain Injury (RSI).

Method. A literature search was performed using terms related to the aforementioned topics and diseases. Only original clinical studies that included at least 20 subjects were eligible.

Results. Fifty-nine studies on CRPS, 73 on FM and 7 on a-specific RSI were identified. The diseases show similarities in age distribution, male-female ratio, pain characteristics and sensory signs and symptoms. Motor, autonomic and trophic changes are frequently reported in CRPS, but only occasionally in FM and RSI. Systemic symptoms are found in patients with CRPS and FM, and in a subgroup of patients with RSI. In all three disorders, symptoms usually start locally, but may spread to other body regions later, which, in the case of FM, is a prerequisite for diagnosis. Disease onset is always, usually, or occasionally of traumatic origin in RSI, CRPS and FM, respectively. Anxiety and depression are more frequent in patients compared to controls, but probably not very different from patients with other pain conditions or chronic diseases.

Conclusions. Apart from some obvious differences between CRPS, FM and RSI, the similarities are conspicuous. The common features of CRPS, FM and a-specific RSI may suggest that a common pathway is involved, but until patients with these type of symptoms are assessed with a uniform assessment procedure, a thorough comparison cannot be made. A systematic evaluation of patients with a suspected diagnosis of CRPS, FM or RSI, may lead to a better appreciation of the differences and similarities in these diseases and help to unravel the underlying mechanisms.     

The role of the bone in complex regional pain syndrome 1—A systematic review

Objective

The aim of this systematic review was to appraise and analyse the knowledge on bone-related biochemical and histological biomarkers in complex regional pain syndrome 1 (CRPS 1).

Database

A total of 7 studies were included in the analysis (biochemical analyses n = 3, animal study n = 1, histological examination n = 3).

Results

Two studies were classified as having a low risk of bias and five studies with a moderate risk of bias. Biochemical analysis indicated an increased bone turnover with increased bone resorption (elevated urinary levels of deoxypyridinoline) and bone formation (increased serum levels of calcitonin, osteoprotegerin and alkaline phosphatase). The animal study reported an increased signalling of proinflammatory tumour necrosis factor 4 weeks postfracture, which did, however, not contribute to local bone loss. Histological examination from biopsies revealed thinning and resorption of cortical bone, rarefication and reduction in trabecular bone and vascular modification in the bone marrow in acute CRPS 1, and replacement of the bone marrow by dystrophic vessels in chronic CRPS 1.

Conclusion

The limited data reviewed revealed certain potential bone-related biomarkers in CRPS. Biomarkers hold the potential to identify patients who may benefit from treatments that influence bone turnover. Thus, this review identifies important areas for future research in CRPS1 patients.     

Can the sensory symptoms of restless legs syndrome be assessed using a qualitative pain questionnaire?

OBJECTIVES: The sensations of restless legs syndrome (RLS) are described as paresthesias and dysesthesias, sensations which also occur in neuropathic pain. Whether validated pain assessment tools can be used to measure the quality and severity of RLS sensations has not been explored. METHODS: Patients with RLS (n=25) completed the RLS severity scale of the International Restless Legs Syndrome Study Group, the McGill Pain Questionnaire (MPQ), and a Visual Analog Scale. Words chosen frequently were also compared with those describing different pain types. RESULTS: The International Restless Legs Syndrome Study Group RLS severity scale score correlated significantly with the Pain Rating Index, and number of words chosen derived from the MPQ, but not with the visual analog scale estimate of pain intensity. The words chosen by patients with RLS showed no significant correlation with words chosen by patients with either neuropathic or nociceptive pain. DISCUSSION: The quality and severity of the sensation of RLS can be measured on the MPQ, and severity calculated from MPQ indices correlates significantly with a standard RLS severity measure. Thus the nonpainful sensations of RLS appear to be a subclinical form of pain.     

Lower β-endorphin content of peripheral blood mononuclear cells in patients with complex regional pain syndrome

Recent studies have demonstrated that immune cell-derived β-endorphin inhibits peripheral nociception. Changes in the β-endorphin content of peripheral blood mononuclear cells (PBMC) were also reported in various human disorders. These findings suggest the modulation of pain by immuno-neural interaction through opioid-dependent mechanisms. The aim of this study, therefore, was to determine whether the levels of β-endorphin in PBMC of patients with complex regional pain syndrome (CRPS) differ from those of healthy subjects. Heparinized venous blood was collected from ten CRPS patients (7 women and 3 men; mean age 39.4 ± 13.0 years) and 13 age-matched healthy volunteers (6 women and 7 men; mean age 38.4 ± 10.8 years). PBMC were separated by density gradient centrifugation. β- endorphin was extracted from the cells in a commercial cell lysis buffer and its concentration was measured by enzyme immunoassay technique. Immunoreactive β-endorphin levels in PBMC from the CRPS patients were significantly lower than those from the healthy volunteers (101.5 ± 57.5 versus 222.1 ± 77.6, P < 0.001), and were not correlated to the present pain intensity or pain duration. The results indicate an altered condition of the immune-linked opioid system underlying CRPS. Further immunological approaches may provide new insight into the pathophysiology of CRPS.