Welcome to the December research update for CRPS and related issues:
J Med Case Reports. 2011 Aug 4;5:349.
Improvement of pain and regional osteoporotic changes in the foot and ankle by low-dose bisphosphonate therapy for complex regional pain syndrome type I: a case series.
Abe Y, Iba K, Takada J, Wada T, Yamashita T.
Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. email@example.com.
Complex regional pain syndrome is characterized by pain, allodynia, hyperalgesia, edema, signs of vasomotor instability, movement disorders, joint stiffness, and regional osteopenia. It is recognized to be difficult to treat, despite various methods of treatment, including physiotherapy, calcitonin, corticosteroids, sympathetic blockade, and nonsteroidal anti-inflammatory drugs. Pathophysiologically, complex regional pain syndrome reveals enhanced regional bone resorption and high bone turnover, and so bisphosphonates, which have a potent inhibitory effect on bone resorption, were proposed for the treatment of complex regional pain syndrome.
A 48-year-old Japanese man with complex regional pain syndrome type I had severe right ankle pain with a visual analog scale score of 59 out of 100 regardless of treatment with physiotherapy and nonsteroidal anti-inflammatory drugs for five months. Radiographs showed marked regional osteoporotic changes and bone scintigraphy revealed a marked increase in radioactivity in his ankle. One month after the start of oral administration of risedronate (2.5 mg per day), his bone pain had fallen from a VAS score of 59 out of 100 to 18 out of 100. Bone scintigraphy at 12 months showed a marked reduction in radioactivity to a level comparable to that in his normal, left ankle. On the basis of these results, the treatment was discontinued at 15 months. At 32 months, our patient had almost no pain and radiographic findings revealed that the regional osteoporotic change had returned to normal.A second 48-year-old Japanese man with complex regional pain syndrome type I had severe right foot pain with a visual analog scale score of 83 out of 100 regardless of treatment with physiotherapy and nonsteroidal anti-inflammatory drugs for nine months. Radiographs showed regional osteoporotic change in his phalanges, metatarsals, and tarsals, and bone scintigraphy revealed a marked increase in radioactivity in his foot. One month after the start of oral administration of alendronate (35 mg per week), his bone pain had fallen from a visual analog scale score of 83 out of 100 to 30 out of 100 and, at nine months, was further reduced to 3 out of 100. The treatment was discontinued at 15 months because of successful pain reduction. At 30 months, our patient had no pain and the radiographic findings revealed marked improvement in regional osteoporotic changes.
We believe low-dose oral administration of bisphosphonate is worth considering for the treatment of idiopathic complex regional pain syndrome type I accompanied by regional osteoporotic change.
Meta-Analysis of the Imaging Techniques for the Diagnosis of Complex Regional Pain Syndrome Type I.
School of Medicine and the Division of Plastic Surgery, University of Louisville, Louisville, KY; and the Department of Orthopedics, University of Michigan, Ann Arbor, MI.
To compare the effectiveness of imaging techniques in aiding and confirming the diagnosis of complex regional pain syndrome (CRPS) type I.
We conducted a meta-analysis of randomized controlled studies that evaluated the effectiveness of 3 different imaging techniques in aiding the diagnosis of CRPS type I. A systematic search in bibliographical databases resulted in 24 studies with 1,916 participants.
To determine the effectiveness of each imaging technique, we determined the average specificity, sensitivity, negative predictive value, and positive predictive value and then statistically compared them using the analysis of variance statistical test, which indicated that compared with magnetic resonance imaging and plain film radiography, triple-phase bone scan had a significantly better sensitivity and negative predictive values. However, there appeared to be no statistical significance between imaging techniques when we evaluated specificity and positive predictive value using the analysis of variance test.
The findings of this meta-analysis support the use of triple-phase bone scan in ruling out CRPS type I, owing to its greater sensitivity and higher negative predictive value than both magnetic resonance imaging and plain film radiography.
J Pain. 2011 Dec 13. [Epub ahead of print]
Changes in Plasma Cytokines and Their Soluble Receptors in Complex Regional Pain Syndrome.
Department of Neurology, Drexel University College of Medicine, Philadelphia, Pennsylvania.
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.
MicroRNA modulation in complex regional pain syndrome.
Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA. firstname.lastname@example.org.
Aberrant expression of small noncoding RNAs called microRNAs (miRNAs) is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS) a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification.
We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions.
Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF), interleukin1 receptor antagonist (IL1Ra) and monocyte chemotactic protein-1 (MCP1) were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with comorbidities such as headache, thyroid disorder and use of narcotics and antiepileptic drugs.
miRNA profiles can be useful in patient stratification and have utility as potential biomarkers for pain. Differentially expressed miRNAs can provide molecular insights into gene regulation and could lead to new therapeutic intervention strategies for CRPS.
2011 Dec 9. [Epub ahead of print]
Sensory signs in complex regional pain syndrome and peripheral nerve injury.
, Maier C
, Baron R
, Tölle T
, Treede RD
, Birbaumer N
, Huge V
, Koroschetz J
, Krumova EK
, Lauchart M
, Maihöfner C
, Richter H
, Westermann A
; the German Research Network on Neuropathic Pain (DFNS) study group
Division of Neurological Pain Research and Therapy, Department of Neurology, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany.
This study determined patterns of sensory signs in complex regional pain syndrome (CRPS) type I and II and peripheral nerve injury (PNI). Patients with upper-limb CRPS-I (n=298), CRPS-II (n=46), and PNI (n=72) were examined with quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain. The majority of patients (66%-69%) exhibited a combination of sensory loss and gain. Patients with CRPS-I had more sensory gain (heat and pressure pain) and less sensory loss than patients with PNI (thermal and mechanical detection, hypoalgesia to heat or pinprick). CRPS-II patients shared features of CRPS-I and PNI. CRPS-I and CRPS-II had almost identical somatosensory profiles, with the exception of a stronger loss of mechanical detection in CRPS-II. In CRPS-I and -II, cold hyperalgesia/allodynia (28%-31%) and dynamic mechanical allodynia (24%-28%) were less frequent than heat or pressure hyperalgesia (36%-44%, 67%-73%), and mechanical hypoesthesia (31%-55%) was more frequent than thermal hypoesthesia (30%-44%). About 82% of PNI patients had at least one type of sensory gain. QST demonstrates more sensory loss in CRPS-I than hitherto considered, suggesting either minimal nerve injury or central inhibition. Sensory profiles suggest that CRPS-I and CRPS-II may represent one disease continuum. However, in contrast to recent suggestions, small fiber deficits were less frequent than large fiber deficits. Sensory gain is highly prevalent in PNI, indicating a better similarity of animal models to human patients than previously thought. These sensory profiles should help prioritize approaches for translation between animal and human research.
Predictors of Pain Relieving Response to Sympathetic Blockade in Complex Regional Pain Syndrome Type 1.
* Consultant Anesthesiologist, Department of Anesthesiology and Pain Management, St. Elisabeth Hospital, Tilburg, The Netherlands. † Research Associate, ‡ Professor, Department of Anesthesiology and Pain Medicine, § Associate Professor, Department of Neurology, Maastricht University Medical Centre, Maastricht, The Netherlands. ‖ Associate Professor, Department of Anesthesiology and Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands. # Biostatistician, Epidemiologist, Department of Clinical Epidemiology and Medical Technology Assessment, University Hospital Maastricht, Maastricht, The Netherlands. ** Consultant Anesthesiologist, Department of Anesthesiology and Multidisciplinary Pain Centre, Hospital Oost-Limburg, Genk, Belgium.
Sympathetic blockade with local anesthetics is used frequently in the management of complex regional pain syndrome type 1(CRPS-1), with variable degrees of success in pain relief. The current study investigated which signs or symptoms of CRPS-1 could be predictive of outcome. The incidence of side effects and complications of sympathetic blockade also were determined prospectively.
A prospective observational study was done of 49 patients with CRPS-1 in one extremity only and for less than 1-yr duration who had severe pain and persistent functional impairment with no response to standard treatment with medication and physical therapy.
Fifteen (31%) patients had good or moderate response. The response rate was not different in patient groups with cold or warm type CRPS-1 or in those with more or less than 1.5°C differential increase in skin temperature after sympathetic blockade. Allodynia and hypoesthesia were negative predictors for treatment success in CRPS-1. There were no symptoms or signs of CRPS-1 that positively predicted treatment success. A majority of patients (84%) experienced transient side effects such as headache, dysphagia, increased pain, backache, nausea, blurred vision, groin pain, hoarseness, and hematoma at the puncture site. No major complications were reported.
The presence of allodynia and hypoesthesia are negative predictors for treatment success. The selection of sympathetic blockade as treatment for CRPS-1 should be balanced carefully between potential success and side effect ratio. The procedure is as likely to cause a transient increase in pain as a decrease in pain. Patients should be informed accordingly.
2011 Dec 1. doi: 10.2165/11595200-000000000-00000. [Epub ahead of print]
Efficacy and Safety of Ketamine in Patients with Complex Regional Pain Syndrome: A Systematic Review.
Department of Anesthesiology, Division of Pain Management, Duke University School of Medicine, Durham, NC, USA.
Despite being a recognized clinical entity for over 140 years, complex regional pain syndrome (CRPS) remains a difficult-to-treat condition. While there have been multiple therapies explored in the treatment of CRPS, NMDA antagonists such as ketamine continue to hold significant interest because of their potential ability to alter the central sensitization noted in chronic pain states. The objective of this review is to identify published literature for evidence of the efficacy and safety of ketamine in the treatment of CRPS. PubMed and the Cochrane Controlled Trials Register were searched (final search 26 May 2011) using the MeSH terms ‘ketamine’, ‘complex regional pain syndrome’, ‘analgesia’ and ‘pain’ in the English literature. The manuscript bibliographies were then reviewed to identify additional relevant papers. Observational trials were evaluated using the Agency for Healthcare Research and Quality criteria; randomized trials were evaluated using the methodological assessment of randomized clinical trials. The search methodology yielded three randomized, placebo-controlled trials, seven observational studies and nine case studies/reports. In aggregate, the data available reveal ketamine as a promising treatment for CRPS. The optimum dose, route and timing of administration remain to be determined. Randomized controlled trials are needed to establish the efficacy and safety of ketamine and to determine its long-term benefit in CRPS.
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about CRPS should consult with a qualified healthcare professional.