Changes in Plasma Cytokines and Their Soluble Receptors in Complex Regional Pain Syndrome

Alexander, Guillermo M.; Peterlin, B. Lee; Perreault, Marielle J.; Grothusen, John R.; Schwartzman, Robert J.

doi:10.1016/j.jpain.2011.10.003

Cited by 69 publications

(63 citation statements)

References 45 publications

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“…23 Healthy controls were utilized by most studies, [14][15][16][17][19][20][21][22] with the exception of 2 that used subjects with fractures or osteoarthritis, 18 and the unaffected arm 2 as controls. The results are presented in figures 2 and 3.…”

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confidence: 99%

“…Only 1 study met all of the applicable criteria on our quality assessment tool 14 and the remainder failed to successfully meet 3 or more of these criteria. The diagnostic criteria used to identify CRPS were found to vary substantially across the included studies.…”

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confidence: 99%

“…Inflammatory factor concentrations in blood were reported in 4 acute CRPS studies, [15][16][17][18] 9 chronic CRPS studies, 2,14,16-22 and 1 mixedduration study. 23 Healthy controls were utilized by most studies, [14][15][16][17][19][20][21][22] with the exception of 2 that used subjects with fractures or osteoarthritis, 18 and the unaffected arm 2 as controls. The results are presented in figures 2 and 3.…”

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Inflammation in complex regional pain syndrome

et al. 2013

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Objectives: We conducted a systematic review of the literature with meta-analysis to determine whether complex regional pain syndrome (CRPS) is associated with a specific inflammatory profile and whether this is dependent on the duration of the condition.Methods: Comprehensive searches of the literature using MEDLINE, Embase, Scopus, Web of Science, and reference lists from published reviews identified articles that measured inflammatory factors in CRPS. Two independent investigators screened titles and abstracts, and performed data extraction and risk of bias assessments. Studies were subgrouped by medium (blood, blister fluid, and CSF) and duration (acute and chronic CRPS). Where possible, meta-analyses of inflammatory factor concentrations were performed and pooled effect sizes were calculated using random-effects models.Results: Twenty-two studies were included in the systematic review and 15 in the meta-analysis.In acute CRPS, the concentrations of interleukin (IL)-8 and soluble tumor necrosis factor receptors I (sTNF-RI) and II (sTNF-RII) were significantly increased in blood. In chronic CRPS, significant increases were found in 1) TNFa, bradykinin, sIL-1RI, IL-1Ra, IL-2, sIL-2Ra, IL-4, IL-7, interferong, monocyte chemoattractant protein-1 (MCP-1), and sRAGE (soluble receptor for advanced glycation end products) in blood; 2) IL-1Ra, MCP-1, MIP-1b, and IL-6 in blister fluid; and 3) IL-1b and IL-6 in CSF. Chronic CRPS was also associated with significantly decreased 1) substance P, sE-selectin, sL-selectin, sP-selectin, and sGP130 in blood; and 2) soluble intercellular adhesion molecule-1 (sICAM-1) in CSF. Most studies failed to meet 3 or more of our quality criteria. Conclusion:CRPS is associated with the presence of a proinflammatory state in the blood, blister fluid, and CSF. Different inflammatory profiles were found for acute and chronic cases. GLOSSARY CI 5 confidence interval; CGRP 5 calcitonin gene-relaxed peptide; CRPS 5 complex regional pain syndrome; ET-1 5 endothelin-1; IL 5 interleukin; IP-10 5 interferon-inducible protein-10; MCP-1 5 monocyte chemoattractant protein-1; NPY 5 neuropeptide Y; PGE2 5 prostaglandin E2; SP 5 substance P; sTNF-R 5 soluble tumor necrosis factor receptor; TNF 5 tumor necrosis factor.Complex regional pain syndrome (CRPS) is characterized by severe pain, allodynia, hyperalgesia, and motor and autonomic signs and symptoms.1 Although the precise etiology of CRPS is unknown, persistent inflammatory activity has been demonstrated in a number of methodologically diverse studies.2-6 Although narrative reviews have attempted to synthesize these results, no systematic review including a rigorous quality assessment of original studies has been conducted. As such, no definitive conclusions can be drawn about the presence of inflammatory activity in CRPS, which limits the identification of potential targets for therapy. Therefore, we conducted a systematic review and meta-analysis of the literature. We aimed firstly to determine whether, in adults, CRPS is associated with a...

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Inflammation in complex regional pain syndrome

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“…Recent literature suggests a crosstalk between pain and inflammation [13][14][15]. Therefore, we investigated a set of 30 inflammation-and pain-related biomarkers to search for potential capability as a biomarker of pain.…”

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confidence: 99%

“…Recent studies have linked inflammatory molecules to pain pathophysiology [10][11][12][13][14][15]. These studies, however, did not focus on the identification of a surrogate Research Article Luchting, Hinske, Rachinger-Adam, Celi, Kreth & Azad marker for pain intensity.…”

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Soluble Intercellular Adhesion Molecule-1: A Potential Biomarker for Pain Intensity in Chronic Pain Patients

et al. 2017

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Aim: Pain therapy is strongly guided by patients' self-reporting. However, when self-reporting is not an option, pain assessment becomes a challenge and may lead to undertreatment of painful conditions. Pain is a complex and multifactorial phenomenon. Recent work has connected pain pathophysiology also with the inflammatory system. We therefore hypothesized that pain intensity could be predicted by cytokine-levels. Patients & methods: In this observational, single-center study, we investigated 30 serum cytokines to predict pain intensity in a screening/follow-up set of 95 chronic pain patients and controls. We then prospectively validated soluble intercellular adhesion molecule-1 (sICAM-1)'s discriminatory capability (n = 21). Results & conclusion: sICAM-1 was significantly associated with patient-reported pain intensity and yielded differential serum levels in patients of varying degrees of pain intensity. Changes in pain ratings over time correlated with changes in sICAM-1 levels. Our findings suggest the possibility of a clinical use of sICAM-1 as a potential biomarker for pain intensity.

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Multi‐analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection

et al. 2013

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BackgroundThe purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms—depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV.MethodsBlood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV−, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers.ResultsCompared with HCV− controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV− group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4–10 plasma immune factors; protein signatures significantly accounted for 19–40% of the variance in depression, anxiety, fatigue, and pain.ConclusionsOverall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric symptoms in adults with or without HCV.

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Changes in Plasma Cytokines and Their Soluble Receptors in Complex Regional Pain Syndrome

Cited by 69 publications

References 45 publications

Inflammation in complex regional pain syndrome

Inflammation in complex regional pain syndrome

Soluble Intercellular Adhesion Molecule-1: A Potential Biomarker for Pain Intensity in Chronic Pain Patients

Multi‐analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection

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