Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1

J George Groeneweg, Frank J P M Huygen, Claudia Heijmans-Antonissen, Sjoerd Niehof, Freek J Zijlstra, J George Groeneweg, Frank J P M Huygen, Claudia Heijmans-Antonissen, Sjoerd Niehof, Freek J Zijlstra

Abstract

Background: In complex regional pain syndrome type 1 (CRPS1) pro-inflammatory mediators and vascular changes play an important role in the sustained development and outcome of the disease. The aim of this study was to determine the involvement of vasoactive substances endothelin-1 (ET-1) and nitric oxide (NO) during early chronic CRPS1.

Methods: Included were 29 patients with CRPS 1 who were diagnosed during the acute stage of their disease and observed during follow-up visits. Disease activity and impairment were determined and artificial suction blisters were made on the CRPS1 and the contralateral extremities for measurements of IL-6, TNF-alpha, ET-1 and nitrate/nitrite (NOx).

Results: The levels of IL-6, TNF-alpha and ET-1 in blister fluid in the CRPS1 extremity versus the contralateral extremity were significantly increased and correlated with each other, whereas NOx levels were decreased.

Conclusion: The NOx/ET-1 ratio appears to be disturbed in the intermediate stage of CRPS, resulting in vasoconstriction and consequently in a diminished tissue blood distribution.

Figures

Figure 1
Figure 1
Distribution of IL-6 and TNF-α. Distribution of a) IL-6 data and b) TNF-α data from 29 CRPS patients, from both the involved and the contralateral extremity. In each plot, the straight line indicates per definition a CRPS to contralateral ratio of 1.00 in case no difference was observed. Values are plotted on logarithmic scales. c) Box plots of these data, indicating the median, 25–75% interval and the ranges of values, excluding outliers. The Wilcoxon signed ranks test was used to assign differences in paired samples (blister fluid obtained from the CRPS1 and the contralateral extremity in the same patient).
Figure 2
Figure 2
Distribution of Endothelin 1 and Nitric Oxide. Distribution of a) ET-1 data from 22 CRPS patients and b) NOx data from 17 CRPS patients. In each plot, the straight line indicates per definition a CRPS to contralateral ratio of 1.00 in case no difference was observed. Values are plotted on linear scales.c) Box plots of these data, indicating the median, 25–75% interval and the ranges of values, excluding outliers. The Wilcoxon signed ranks test was used to assign differences in paired samples (blister fluid obtained from the CRPS1 and the contralateral extremity in the same patient).

References

    1. Janig W, Baron R. Complex regional pain syndrome: mystery explained? Lancet Neurol. 2003;2:687–697. doi: 10.1016/S1474-4422(03)00557-X.
    1. Baron R, Janig W. Complex regional pain syndromes--how do we escape the diagnostic trap? Lancet. 2004;364:1739–1741. doi: 10.1016/S0140-6736(04)17416-3.
    1. Bruehl S, Harden RN, Galer BS, Saltz S, Bertram M, Backonja M, Gayles R, Rudin N, Bhugra MK, Stanton-Hicks M. 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. doi: 10.1016/S0304-3959(99)00011-1.
    1. Bruehl S, Harden RN, Galer BS, Saltz S, Backonja M, Stanton-Hicks M. Complex regional pain syndrome: are there distinct subtypes and sequential stages of the syndrome? Pain. 2002;95:119–124. doi: 10.1016/S0304-3959(01)00387-6.
    1. Huygen FJ, de Bruijn AG, Klein J, Zijlstra FJ. Neuroimmune alterations in the complex regional pain syndrome. Eur J Pharmacol. 2001;429:101–113. doi: 10.1016/S0014-2999(01)01310-3.
    1. Dijkstra PU, Groothoff JW, ten Duis HJ, Geertzen JH. Incidence of complex regional pain syndrome type I after fractures of the distal radius. Eur J Pain. 2003;7:457–462. doi: 10.1016/S1090-3801(03)00015-6.
    1. Mos M, Bruijn AGJ, Huygen FJPM, Dieleman JP, Stricker BHC, Sturkenboom MCJM. The incidence of Complex Regional Pain Syndrome: a population-based study. Submitted. 2006.
    1. Birklein F. Complex regional pain syndrome. J Neurol. 2005;252:131–138. doi: 10.1007/s00415-005-0737-8.
    1. Huygen FJ, De Bruijn AG, De Bruin MT, Groeneweg JG, Klein J, Zijlstra FJ. Evidence for local inflammation in complex regional pain syndrome type 1. Mediators Inflamm. 2002;11:47–51. doi: 10.1080/09629350210307.
    1. Schwartzman RJ, Popescu A. Reflex sympathetic dystrophy. Curr Rheumatol Rep. 2002;4:165–169.
    1. Wasner G, Heckmann K, Maier C, Baron R. Vascular abnormalities in acute reflex sympathetic dystrophy (CRPS I): complete inhibition of sympathetic nerve activity with recovery. Arch Neurol. 1999;56:613–620. doi: 10.1001/archneur.56.5.613.
    1. Wasner G, Schattschneider J, Heckmann K, Maier C, Baron R. Vascular abnormalities in reflex sympathetic dystrophy (CRPS I): mechanisms and diagnostic value. Brain. 2001;124:587–599. doi: 10.1093/brain/124.3.587.
    1. Baamonde A, Lastra A, Villazon M, Bordallo J, Hidalgo A, Menendez L. Involvement of endogenous endothelins in thermal and mechanical inflammatory hyperalgesia in mice. Naunyn Schmiedebergs Arch Pharmacol. 2004;369:245–251. doi: 10.1007/s00210-003-0841-1.
    1. Dahlof B, Gustafsson D, Hedner T, Jern S, Hansson L. Regional haemodynamic effects of endothelin-1 in rat and man: unexpected adverse reaction. J Hypertens. 1990;8:811–817. doi: 10.1097/00004872-199009000-00004.
    1. Oda M, Yokomori H, Han JY. Regulatory mechanisms of hepatic microcirculation. Clin Hemorheol Microcirc. 2003;29:167–182.
    1. Leslie SJ, Rahman MQ, Denvir MA, Newby DE, Webb DJ. Endothelins and their inhibition in the human skin microcirculation: ET[1-31], a new vasoconstrictor peptide. Br J Clin Pharmacol. 2004;57:720–725. doi: 10.1111/j.1365-2125.2004.02074.x.
    1. Huygen FJ, Niehof S, Zijlstra FJ, van Hagen PM, van Daele PL. Successful treatment of CRPS 1 with anti-TNF. J Pain Symptom Manage. 2004;27:101–103. doi: 10.1016/j.jpainsymman.2003.12.006.
    1. Alonso D, Radomski MW. The nitric oxide-endothelin-1 connection. Heart Fail Rev. 2003;8:107–115. doi: 10.1023/A:1022155206928.
    1. Yoshizumi M, Perrella MA, Burnett JC, Jr., Lee ME. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. Circ Res. 1993;73:205–209.
    1. Patel JN, Jager A, Schalkwijk C, Corder R, Douthwaite JA, Yudkin JS, Coppack SW, Stehouwer CD. Effects of tumour necrosis factor-alpha in the human forearm: blood flow and endothelin-1 release. Clin Sci (Lond) 2002;103:409–415.
    1. Matsushima H, Yamada N, Matsue H, Shimada S. The effects of endothelin-1 on degranulation, cytokine, and growth factor production by skin-derived mast cells. Eur J Immunol. 2004;34:1910–1919. doi: 10.1002/eji.200424912.
    1. Huygen FJ, Ramdhani N, Van Toorenenbergen A, Klein J, Zijlstra FJ. Mast cells are involved in inflammatory reactions during Complex Regional Pain Syndrome type 1. Immunol Lett. 2004;91:147–154. doi: 10.1016/j.imlet.2003.11.013.
    1. Oerlemans HM, Oostendorp RA, de Boo T, van der Laan L, Severens JL, Goris JA. Adjuvant physical therapy versus occupational therapy in patients with reflex sympathetic dystrophy/complex regional pain syndrome type I. Arch Phys Med Rehabil. 2000;81:49–56. doi: 10.1053/apmr.2000.0810049.
    1. Prens EP, Benne K, van Damme J, Bakkus M, Brakel K, Benner R, van Joost T. Interleukin-1 and interleukin-6 in psoriasis. J Invest Dermatol. 1990;95:121S–124S. doi: 10.1111/1523-1747.ep12874991.
    1. Macdonald N, Cumberbatch M, Singh M, Moggs JG, Orphanides G, Dearman RJ, Griffiths CE, Kimber I. Proteomic analysis of suction blister fluid isolated from human skin. Clin Exp Dermatol. 2006;31:445–448. doi: 10.1111/j.1365-2230.2006.02078.x.
    1. Michiels JJ, Zijlstra FJ. Prostaglandin cyclooxygenase products but not thromboxane A2 are involved in the pathogenesis of erythromelalgia in thrombocythaemia. Mediators Inflamm. 1993;2:385 –3389.
    1. Reilly DM, Green MR. Eicosanoid and cytokine levels in acute skin irritation in response to tape stripping and capsaicin. Acta Derm Venereol. 1999;79:187–190. doi: 10.1080/000155599750010931.
    1. Heijmans-Antonissen C, Wesseldijk F, Munnikes RJ, Huygen FJ, van der Meijden P, Hop WC, Hooijkaas H, Zijlstra FJ. 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;2006:28398.
    1. Munnikes RJ, Muis C, Boersma M, Heijmans-Antonissen C, Zijlstra FJ, Huygen FJ. Intermediate stage complex regional pain syndrome type 1 is unrelated to proinflammatory cytokines. Mediators Inflamm. 2005;2005:366–372. doi: 10.1155/MI.2005.366.
    1. Bonifati C, Mussi A, Carducci M, Pittarello A, D'Auria L, Venuti A, Bagnato A, Salani D, Fazio M, Ameglio F. Endothelin-1 levels are increased in sera and lesional skin extracts of psoriatic patients and correlate with disease severity. Acta Derm Venerol. 1998;78:22–26. doi: 10.1080/00015559850135779.
    1. Eisenberg E, Erlich T, Zinder O, Lichinsky S, Diamond E, Pud D, Davar G. Plasma endothelin-1 levels in patients with complex regional pain syndrome. Eur J Pain. 2004;8:533–538. doi: 10.1016/j.ejpain.2003.12.003.
    1. El Melegy NT, Ali ME, Awad EM. Plasma levels of endothelin-1, angiotensin II, nitric oxide and prostaglandin E in the venous and cavernosal blood of patients with erectile dysfunction. BJU Int. 2005;96:1079–1086. doi: 10.1111/j.1464-410X.2005.05780.x.
    1. Pache M, Schwarz HA, Kaiser HJ, Wuest P, Kloti M, Dubler B, Flammer J. Elevated plasma endothelin-1 levels and vascular dysregulation in patients with rheumatoid arthritis. Med Sci Monit. 2002;8:616–619.
    1. Haq A, El-Ramahi K, Al-Dalaan A, Al-Sedairy ST. Serum and synovial fluid concentrations of endothelin-1 in patients with rheumatoid arthritis. J Med. 1999;30:51–60.
    1. Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S, Ciolkiewicz M. A study on vascular endothelial growth factor and endothelin-1 in patients with extra-articular involvement of rheumatoid arthritis. Clin Rheumatol. 2005. pp. 1–6.
    1. Wakisaka N, Kubota T, Ando K, Aihara M, Inoue H, Ishida H. Endothelin-1 kinetics in plasma, urine, and blister fluid in burn patients. Ann Plast Surg. 1996;37:305–309. doi: 10.1097/00000637-199609000-00012.
    1. Hartrick CT. Increased production of nitric oxide stimulated by interferon-gamma from peripheral blood monocytes in patients with complex regional pain syndrome. Neurosci Lett. 2002;323:75–77. doi: 10.1016/S0304-3940(02)00112-X.
    1. Alonso D, Radomski MW. Nitric oxide, platelet function, myocardial infarction and reperfusion therapies. Heart Fail Rev. 2003;8:47–54. doi: 10.1023/A:1022194921040.
    1. Erkan E, Devarajan P, Kaskel F. Role of nitric oxide, endothelin-1, and inflammatory cytokines in blood pressure regulation in hemodialysis patients. Am J Kidney Dis. 2002;40:76–81. doi: 10.1053/ajkd.2002.33915.
    1. Oerlemans HM, Goris RJ, Oostendorp RA. Impairment level sumscore in reflex sympathetic dystrophy of one upper extremity. Arch Phys Med Rehabil. 1998;79:979–990. doi: 10.1016/S0003-9993(98)90098-3.
    1. Maeda S, Miyauchi T, Kakiyama T, Sugawara J, Iemitsu M, Irukayama-Tomobe Y, Murakami H, Kumagai Y, Kuno S, Matsuda M. Effects of exercise training of 8 weeks and detraining on plasma levels of endothelium-derived factors, endothelin-1 and nitric oxide, in healthy young humans. Life Sci. 2001;69:1005–1016. doi: 10.1016/S0024-3205(01)01192-4.
    1. Tanabe K, Yamamoto A, Suzuki N, Yokoyama Y, Osada N, Nakayama M, Akashi Y, Seki A, Samejima H, Oya M, Murabayashi T, Omiya K, Itoh H, Miyake F, Murayama M. Physiological role of endothelin-1 in nonworking muscles during exercise in healthy subjects. Jpn Circ J. 2000;64:27–31. doi: 10.1253/jcj.64.27.
    1. Maeda S, Tanabe T, Miyauchi T, Otsuki T, Sugawara J, Iemitsu M, Kuno S, Ajisaka R, Yamaguchi I, Matsuda M. Aerobic exercise training reduces plasma endothelin-1 concentration in older women. J Appl Physiol. 2003;95:336–341.
    1. Maeda S, Miyauchi T, Iemitsu M, Tanabe T, Irukayama-Tomobe Y, Goto K, Yamaguchi I, Matsuda M. Involvement of endogenous endothelin-1 in exercise-induced redistribution of tissue blood flow: an endothelin receptor antagonist reduces the redistribution. Circulation. 2002;106:2188–2193. doi: 10.1161/01.CIR.0000038362.16740.A2.
    1. Malmstrom RE, Weitzberg E. Endothelin and nitric oxide in inflammation: could there be a need for endothelin blocking anti-inflammatory drugs? J Hypertens. 2004;22:27–29. doi: 10.1097/00004872-200401000-00006.
    1. Nelson JB. Endothelin receptor antagonists. World J Urol. 2005;23:19 –127. doi: 10.1007/s00345-004-0478-9.
    1. Girgis RE, Champion HC, Diette GB, Johns RA, Permutt S, Sylvester JT. Decreased exhaled nitric oxide in pulmonary arterial hypertension: response to bosentan therapy. Am J Respir Crit Care Med. 2005;172:352–357. doi: 10.1164/rccm.200412-1684OC.
    1. Meurs H, Maarsingh H, Zaagsma J. Arginase and asthma: novel insights into nitric oxide homeostasis and airway hyperresponsiveness. Trends Pharmacol Sci. 2003;24:450–455. doi: 10.1016/S0165-6147(03)00227-X.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren