The Journal of Pain
Volume 13, Issue 1 , Pages 10-20, January 2012
Changes in Plasma Cytokines and Their Soluble Receptors in Complex Regional Pain Syndrome
Guillermo M. Alexander, B. Lee Peterlin, Marielle J. Perreault, John R. Grothusen, Robert J. Schwartzman (All from the Dept of Neurology at Drexel, except for Peterlin from the Dept of Neurology at Hopkins)
Abstract
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.
[less laudatory drexel associations...]
Volume 13, Issue 1 , Pages 10-20, January 2012
Changes in Plasma Cytokines and Their Soluble Receptors in Complex Regional Pain Syndrome
Guillermo M. Alexander, B. Lee Peterlin, Marielle J. Perreault, John R. Grothusen, Robert J. Schwartzman (All from the Dept of Neurology at Drexel, except for Peterlin from the Dept of Neurology at Hopkins)
Abstract
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.
References
- . Chemokines, chemokine receptors and pain. Trends Immunol. 2005;26:529–534
- . Changes in cerebrospinal fluid levels of proinflammatory cytokines in CRPS. Pain. 2005;116:213–219
- . Changes in immune and glial markers in the CSF of patients with Complex Regional Pain Syndrome. Brain Behav Immun. 2007;21:668–676
- . Successful intravenous regional block with low-dose tumor necrosis factor-alpha antibody infliximab for treatment of complex regional pain syndrome 1. Anesth Analg.2007;105:1148–1151
- . The important role for neuropeptides in complex regional pain syndrome.Neurology. 2001;57:2179–2184
- . External validation of IASP diagnostic criteria for Complex Regional Pain Syndrome and proposed research diagnostic criteria. International Association for the Study of Pain. Pain.1999;81:147–154
- . Complex regional pain syndrome: Are there distinct subtypes and sequential stages of the syndrome?. Pain. 2002;95:119–124
- . The scree test for the number of factors. Multivariate Behav Res. 1966;1:245–276
- . Neuropathic pain: A maladaptive response of the nervous system to damage. Annu Rev Neurosci. 2009;32:1–32
- . The role of neuroinflammation and neuroimmune activation in persistent pain. Pain. 2001;90:1–6
- . Multi-day low dose ketamine infusion for the treatment of complex regional pain syndrome. Pain Physician. 2005;8:175–179
- . Validation of proposed diagnostic criteria (the "Budapest Criteria") for Complex Regional Pain Syndrome. Pain. 2010;150:268–274
- . Multiplex bead array assay for detection of 25 soluble cytokines in blister fluid of patients with complex regional pain syndrome type 1. Mediators Inflamm. 2006;2006:1–8
- . Reproducibility and influence of test modality order on thermal perception and thermal pain thresholds in quantitative sensory testing. Clin Neurophysiol. 2010;121:1878–1885
- . Evidence for local inflammation in complex regional pain syndrome type 1. Mediators Inflamm. 2002;11:47–51
- . Successful treatment of CRPS 1 with anti-TNF. J Pain Symptom Manage. 2004;27:101–103
- . Mast cells are involved in inflammatory reactions during Complex Regional Pain Syndrome type 1. Immunol Lett. 2004;91:147–154
- . Complex regional pain syndrome: Mystery explained?. Lancet Neurol. 2003;2:687–697
- . The application of electronic computers to factor analysis. Educ Psychol Meas. 1960;20:141–151
- . TNF-alpha in CRPS and ‘normal’ trauma – Significant differences between tissue and serum. Pain. 2011;152:285–290
- . Mechanical hyperalgesia in complex regional pain syndrome: A role for TNF-alpha?. Neurology. 2005;65:311–313
- . Role of the immune system in chronic pain. Nat Rev Neurosci. 2005;6:521–532
- . Immune and glial cell factors as pain mediators and modulators. Exp Neurol.2005;192:444–462
- . Intermediate stage complex regional pain syndrome type 1 is unrelated to proinflammatory cytokines. Mediators Inflamm. 2005;2005:366–372
- . Analysis of cerebrospinal fluid inflammatory mediators in chronic complex regional pain syndrome related dystonia. Clin J Pain. 2008;24:30–34
- . Is reflex sympathetic dystrophy/complex regional pain syndrome type I a small-fiber neuropathy?. Ann Neurol. 2009;65:629–638
- . Inflammatory mediators are altered in the acute phase of posttraumatic complex regional pain syndrome. Clin J Pain. 2006;22:235–239
- . Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups. Eur J Med Res.2009;14:130–135
- . Neuropathic central pain: Epidemiology, etiology, and treatment options.Arch Neurol. 2001;58:1547–1550
- . Thalidomide has activity in treating complex regional pain syndrome. Arch Intern Med. 2003;163:1487–1488
- . The pathophysiology of complex regional pain syndrome. Expert Rev Neurother.2006;6:669–681
- . The natural history of complex regional pain syndrome. Clin J Pain. 2009;25:273–280
- . Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: A double-blind placebo controlled study. Pain. 2009;147:107–115
- . Efficacy of 5-day continuous lidocaine infusion for the treatment of refractory complex regional pain syndrome. Pain Med. 2009;10:401–412
- . Recent findings on how proinflammatory cytokines cause pain: Peripheral mechanisms in inflammatory and neuropathic hyperalgesia. Neurosci Lett. 2004;361:184–187
- . Reflex sympathetic dystrophy: Changing concepts and taxonomy. Pain. 1995;63:127–133
- . Differential expression patterns of cytokines in complex regional pain syndrome. Pain. 2007;132:195–205
- . Innate cytokine profile in patients with complex regional pain syndrome is normal. Pain. 2001;91:259–261
- . Determinants of thermal pain thresholds in normal subjects. Clin Neurophysiol. 2008;119:2389–2395
- . Glia: A novel drug discovery target for clinical pain. Nat Rev Drug Discov. 2003;2:973–985
- . Immune regulation of central nervous system functions: From sickness responses to pathological pain. J Intern Med. 2005;257:139–155
- . Sodium channels and pain. Proc Natl Acad Sci U S A. 1999;96:7635–7639
- White paper – technical report. The SPSS TwoStep Cluster Component.http://www.spss.ch/upload/1122644952_The%20SPSS%20TwoStep%20Cluster%20Component.pdf. Accessed November 30, 2011
- . Neuronal plasticity: Increasing the gain in pain. Science. 2000;288:1765–1769
- . Thermal testing: Normative data and repeatability for various test algorithms. J Neurol Sci.1994;125:39–45
- . Heat pain thresholds: Normative data and repeatability. Pain. 1995;60:329–332
- . Immunomodulation by thalidomide: Systematic review of the literature and of unpublished observations. J Inflamm. 1995;46:177–211
[less laudatory drexel associations...]
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