Klinische Neurophysiologie 2012; 43(04): 266-273
DOI: 10.1055/s-0032-1327670
Originalia
© Georg Thieme Verlag KG Stuttgart · New York

Aktuelles zur Pathophysiologie und Therapie des komplex-regionalen Schmerzsyndroms (CRPS)

Recent Concepts of Pathophysiology and Treatment of Complex Regional Pain Syndrome (CRPS)
M. Fechir
1   Klinik und Poliklinik für Neurologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
,
F. Birklein
1   Klinik und Poliklinik für Neurologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz
› Author Affiliations
Further Information

Publication History

Publication Date:
20 December 2012 (online)

Zusammenfassung

Bei etwa 2% der Patienten kommt es, meist nach einem Trauma einer Extremität, einer Läsion eines periphereren Nervs oder des zentralen Nervensystems, zum Auftreten charakteristischer Symptomkonstellationen mit schmerzhafter Funktionseinschränkung, die als „komplex-regionales Schmerzsyndrom“ (CRPS) bezeichnet werden. Die Symptome bestehen aus Störungen der Sensibilität (z. B. Taubheitsgefühle, Schmerzen, Hyperalgesie), der Motorik (z. B. Kraftminderung, Tremor, Dystonie), des autonomen Nervensystems (z. B. Änderungen der Hauttemperatur, des Schwitzens sowie Verfärbung der Haut) und der Trophik (z. B. verändertes Wachstum von Haaren, Finger-/Fußnägeln). Komplex-regionale Schmerzsyndrome werden in Anhängigkeit des Nachweises einer Nervenläsion unterteilt in Typ I ohne Läsion und Typ II mit Nervenläsion. Jedoch erscheint zudem eine Einteilung nach der Hauttemperatur zu Beginn der Erkrankung sinnvoll, da dies auch pathophysiologische Aspekte berücksichtigt („primär warmes“ bzw. „primär kaltes CRPS“). Dank intensiver Forschungen der letzten Jahre konnten die Mechanismen des CRPS zunehmend besser erklärt werden. Die unterschiedlichen beteiligten pathophysiologischen Prozesse sind in der vorliegenden Übersichtsarbeit dargestellt. Um eine Chronifizierung und bleibende Funktionseinschränkung zu vermeiden bzw. eine gute Extremtitätenfunktion wiederherzustellen, ist möglichst frühzeitig eine individuell angepasste, multi-disziplinäre Therapie unter Einbeziehung medikamentöser und nicht-medikamentöser Verfahren anzustreben. Die zur Verfügung stehenden Optionen werden in dieser Arbeit ebenfalls vorgestellt.

Abstract

Some patients (approx. 2%) develop a characteristic constellation of symptoms with a painful reduction of extremity function following limb trauma or lesions of the peripheral or central nervous system. This extraordinary painful condition is denominated as „complex regional pain syndrome“ (CRPS). Symptoms regularly observed are motor (e. g., paresis, tremor, dystonia), sensory (e. g., hypaesthesia, pain), and autonomic disturbances (e. g., differences of skin temperature, altered sweating, change of skin colour) as well as trophic alterations (e. g., altered growth of hair or nails). Complex regional pain syndromes (CRPS) are subclassified depending on a clinically obvious nerve lesion. CRPS I is diagnosed in the absence of a nerve lesion, CRPS II in the presence of one. However, a classification considering differences of skin temperature at onset of the disease seems also appealing as it rather reflects pathophysiological aspects („primary warm“ or, respectively, „primary cold CRPS“). Intensive research during the last years has improved our understanding of the mechanisms leading to CRPS. These pathophysiological processes are presented in this review. An early multi-disciplinary therapeutic approach with medical and non-medical treatment is required to avoid chronification and persisting impairment of function of the affected extremity. Effective treatment options are also highlighted in this article.

 
  • Literatur

  • 1 Birklein F, Riedl B, Claus D et al. Pattern of autonomic dysfunction in time course of complex regional pain syndrome. Clin Auton Res Apr 1998; 8 (02) 79-85
  • 2 Leriche R. De la causalgie envisagée comme une névrite du sympathique et de son traitement par la dénudation et l’excision des plexus nerveux périartériels. Presse Med 1916; 24: 178-180
  • 3 Mitchell SW, Morehouse GR, Keen WW. Gunshot wounds and other injuries of nerves. New York: Lipincott JP; 1864
  • 4 Livingston WK. Pain mechanisms. A physiologic interpretation of causalgia and its relevant states. New York: Macmillan; 1944
  • 5 Evans JA. Reflex sympathetic dystrophy. Surg Clin North Am 1946; 26: 435-448
  • 6 Sudeck P. Über die akute entzündliche Knochenatrophie. Arch Klin Chir 1900; 62: 144-156
  • 7 Sudeck P. Die so genannte akute Knochenatrophie als Entzündungsvorgang. Der Chirurg 1942; 15: 449-457
  • 8 Stanton-Hicks M, Janig W, Hassenbusch S et al. Reflex sympathetic dystrophy: changing concepts and taxonomy. Pain Oct 1995; 63 (01) 127-133
  • 9 Bruehl S, Harden RN, Galer BS et al. Complex regional pain syndrome: are there distinct subtypes and sequential stages of the syndrome?. Pain Jan 2002; 95 (1–2) 119-124
  • 10 Birklein F, Kunzel W, Sieweke N. Despite clinical similarities there are significant differences between acute limb trauma and complex regional pain syndrome I (CRPS I). Pain Aug 2001; 93 (02) 165-171
  • 11 Eberle T, Doganci B, Kramer HH et al. Warm and cold complex regional pain syndromes: differences beyond skin temperature?. Neurology Feb 10 2009; 72 (06) 505-512
  • 12 Vaneker M, Wilder-Smith OH, Schrombges P et al. Patients initially diagnosed as ‘warm’ or ‘cold’ CRPS 1 show differences in central sensory processing some eight years after diagnosis: a quantitative sensory testing study. Pain May 2005; 115 (1–2) 204-211
  • 13 Harden RN, Bruehl S, Perez RS et al. Validation of proposed diagnostic criteria (the “Budapest Criteria”) for Complex Regional Pain Syndrome. Pain Aug 2010; 150 (02) 268-274
  • 14 Baron R, Janig W. Complex regional pain syndromes – how do we escape the diagnostic trap?. Lancet Nov 13–19 2004; 364 (9447) 1739-1741
  • 15 Wuppenhorst N, Maier C, Frettloh J et al. Sensitivity and specificity of 3-phase bone scintigraphy in the diagnosis of complex regional pain syndrome of the upper extremity. Clin J Pain Mar-Apr 2010; 26 (03) 182-189
  • 16 Schurmann M, Zaspel J, Lohr P et al. Imaging in early posttraumatic complex regional pain syndrome: a comparison of diagnostic methods. Clin J Pain Jun 2007; 23 (05) 449-457
  • 17 Gradl G, Steinborn M, Wizgall I et al. Acute CRPS I (morbus sudeck) following distal radial fractures – methods for early diagnosis. Zentralbl Chir Dec 2003; 128 (12) 1020-1026
  • 18 Graif M, Schweitzer ME, Marks B et al. Synovial effusion in reflex sympathetic dystrophy: an additional sign for diagnosis and staging. Skeletal Radiol May 1998; 27 (05) 262-265
  • 19 Wasner G, Schattschneider J, Baron R. Skin temperature side differences – a diagnostic tool for CRPS?. Pain Jul 2002; 98 (1–2) 19-26
  • 20 Krumova EK, Frettloh J, Klauenberg S et al. Long-term skin temperature measurements – a practical diagnostic tool in complex regional pain syndrome. Pain Nov 15 2008; 140 (01) 8-22
  • 21 Harden RN, Bruehl S, Perez RS et al. Development of a severity score for CRPS. Pain Dec 2010; 151 (03) 870-876
  • 22 Birklein F, Riedl B, Sieweke N et al. Neurological findings in complex regional pain syndromes – analysis of 145 cases. Acta Neurol Scand Apr 2000; 101 (04) 262-269
  • 23 Maihofner C, Handwerker HO, Birklein F. Functional imaging of allodynia in complex regional pain syndrome. Neurology Mar 14 2006; 66 (05) 711-717
  • 24 Maihofner C, Handwerker HO, Neundorfer B et al. Mechanical hyperalgesia in complex regional pain syndrome: a role for TNF-alpha?. Neurology Jul 26 2005; 65 (02) 311-313
  • 25 Maier C, Baron R, Tolle TR et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain Sep 2010; 150 (03) 439-450
  • 26 Frettloh J, Huppe M, Maier C. Severity and specificity of neglect-like symptoms in patients with complex regional pain syndrome (CRPS) compared to chronic limb pain of other origins. Pain Sep 2006; 124 (1–2) 184-189
  • 27 Lewis JS, Kersten P, McPherson KM et al. Wherever is my arm? Impaired upper limb position accuracy in complex regional pain syndrome. Pain Jun 2010; 149 (03) 463-469
  • 28 Reinersmann A, Haarmeyer GS, Blankenburg M et al. Left is where the L is right. Significantly delayed reaction time in limb laterality recognition in both CRPS and phantom limb pain patients. Neurosci Lett Dec 17 2010; 486 (03) 240-245
  • 29 Forderreuther S. Sailer U, Straube A. Impaired self-perception of the hand in complex regional pain syndrome (CRPS). Pain Aug 2004; 110 (03) 756-761
  • 30 Veldman PH, Reynen HM, Arntz IE et al. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. Lancet Oct 23 1993; 342 (8878) 1012-1016
  • 31 Birklein F, Riedl B, Claus D et al. Cutaneous norepinephrine application in complex regional pain syndrome. Eur J Pain 1997; 1 (02) 123-132
  • 32 Deuschl G, Blumberg H, Lucking CH.. Tremor in reflex sympathetic dystrophy. Arch Neurol Dec 1991; 48 (12) 1247-1252
  • 33 Jankovic J, Van der Linden C. Dystonia and tremor induced by peripheral trauma: predisposing factors. J Neurol Neurosurg Psychiatry Dec 1988; 51 (12) 1512-1519
  • 34 van Hilten JJ, van de Beek WJ, Roep BO. Multifocal or generalized tonic dystonia of complex regional pain syndrome: a distinct clinical entity associated with HLA-DR13. Ann Neurol Jul 2000; 48 (01) 113-116
  • 35 Maihöfner C, Baron R, DeCol R et al. The motor system shows adaptive changes in complex regional pain syndrome. Brain Oct 2007; 130 (Pt 10) 2671-2687
  • 36 Rather LJ. Disturbance of function (functio laesa): the legendary fifth cardinal sign of inflammation, added by Galen to the four cardinal signs of Celsus. Bull N Y Acad Med Mar 1971; 47 (03) 303-322
  • 37 Uceyler N, Eberle T, Rolke R et al. Differential expression patterns of cytokines in complex regional pain syndrome. Pain Nov 2007; Nov 132 (1–2) 195-205
  • 38 Alexander GM, van Rijn MA, van Hilten JJ et al. Changes in cerebrospinal fluid levels of pro-inflammatory cytokines in CRPS. Pain Aug 2005; 116 (03) 213-219
  • 39 Schafers M, Lee DH, Brors D et al. Increased sensitivity of injured and adjacent uninjured rat primary sensory neurons to exogenous tumor necrosis factor-alpha after spinal nerve ligation. J Neurosci Apr 1 2003; 23 (07) 3028-3038
  • 40 Opree A, Kress M. Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 but not IL-8 in the development of heat hyperalgesia: effects on heat-evoked calcitonin gene-related peptide release from rat skin. J Neurosci Aug 15 2000; 20 (16) 6289-6293
  • 41 Nickel FT, Maihöfner C. Neuroimages. Hypertrichosis in alopecia universalis and complex regional pain syndrome. Neurology Oct 19 2010; 75 (16) 1483
  • 42 Wasner G, Heckmann K, Maier C et al. Vascular abnormalities in acute reflex sympathetic dystrophy (CRPS I): complete inhibition of sympathetic nerve activity with recovery.. Arch Neurol May 1999; 56 (05) 613-620
  • 43 Barnsley N, McAuley JH, Mohan R et al. The rubber hand illusion increases histamine reactivity in the real arm. Curr Biol Dec 6 2011; 21 (23) R945-R946
  • 44 Baron R, Schattschneider J, Binder A et al. Relation between sympathetic vasoconstrictor activity and pain and hyperalgesia in complex regional pain syndromes: a case-control study. Lancet May 11 2002; 359 (9318) 1655-1660
  • 45 Ali Z, Raja SN, Wesselmann U et al. Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain. Pain Nov 2000; 88 (02) 161-168
  • 46 Raja SN, Treede RD, Davis KD et al. Systemic alpha-adrenergic blockade with phentolamine: a diagnostic test for sympathetically maintained pain. Anesthesiology Apr 1991; 74 (04) 691-698
  • 47 van Eijs F, Geurts J, van Kleef M et al. Predictors of pain relieving response to sympathetic blockade in complex regional pain syndrome type 1. Anesthesiology Jan 2012; 116 (01) 113-121
  • 48 Cepeda MS, Carr DB, Lau J. Local anesthetic sympathetic blockade for complex regional pain syndrome. Cochrane Database Syst Rev Oct 19 2005; (04) CD004598
  • 49 Calder JS, Holten I, McAllister RM. Evidence for immune system involvement in reflex sympathetic dystrophy. J Hand Surg Br Apr 1998; 23 (02) 147-150
  • 50 Kohr D, Singh P, Tschernatsch M et al. Autoimmunity against the β(2) adrenergic receptor and muscarinic-2 receptor in complex regional pain syndrome. Pain Dec 2011; 152 (12) 2690-2700
  • 51 Goebel A, Baranowski A, Maurer K et al. Intravenous immunoglobulin treatment of the complex regional pain syndrome: a randomized trial. Ann Intern Med Feb 2 2010; 152 (03) 152-158
  • 52 Maihofner C, Handwerker HO, Neundorfer B et al. Patterns of cortical reorganization in complex regional pain syndrome. Neurology Dec 23 2003; 61 (12) 1707-1715
  • 53 Maihofner C, Handwerker HO, Neundorfer B et al. Cortical reorganiza­tion during recovery from complex regional pain syndrome. Neurology Aug 24 2004; 63 (04) 693-701
  • 54 Pleger B, Tegenthoff M, Ragert P et al. Sensorimotor retuning [corrected] in complex regional pain syndrome parallels pain reduction. Ann Neurol Mar 2005; 57 (03) 425-429
  • 55 Peltz E, Seifert F, Lanz S et al. Impaired hand size estimation in CRPS. J Pain Oct 2011; 12 (10) 1095-1101
  • 56 Sumitami M, Shibata M, Iwakura T et al. Pathologic pain distorts visuospatial perception. Neurology Jan 9 2007; 68 (02) 152-154
  • 57 Moseley GL, Gallace A, Spence C. Space-based, but not arm-based, shift in tactile processing in complex regional pain syndrome and its relationship to cooling of the affected limb. Brain Nov 2009; 132 (Pt 11) 3142-3151
  • 58 van Hilten JJ. Movement disorders in complex regional pain syndrome. Pain Med. Pain Med Aug 2010; 11 (08) 1274-1277
  • 59 Schwenkreis P, Janssen F, Rommel O et al. Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand. Neurology Aug 26 2003; 61 (04) 515-519
  • 60 Eisenberg E, Chistyakov AV, Yudashkin M et al. Evidence for cortical hyperexcitability of the affected limb representation area in CRPS: a psychophysical and transcranial magnetic stimulation study. Pain Jan 2005; 113 (1–2) 99-105
  • 61 Avanzino L, Martino D, van de Warrenburg BP et al. Cortical excitability is abnormal in patients with the “fixed dystonia” syndrome. Mov Disord Apr 15 2008; 23 (05) 646-652
  • 62 Kemler MA, van de Vusse AC, van den Berg-Loonen EM et al. HLA-DQ1 associated with reflex sympathetic dystrophy. Neurology Oct 12 1999; 53 (06) 1350-1351
  • 63 van de Beek WJ, Roep BO, van der Slik AR et al. Susceptibility loci for complex regional pain syndrome. Pain May 2003; 103 (1/2) 93-97
  • 64 de Rooij AM, de Mos M, van Hilten JJ et al. Increased risk of complex regional pain syndrome in siblings of patients?. J Pain Dec 2009; 10 (12) 1250-1255
  • 65 Verdugo RJ, Ochoa JL. Abnormal movements in complex regional pain syndrome: assessment of their nature. Muscle Nerve Feb 2000; 23 (02) 198-205
  • 66 Beerthuizen A, van t Spijker A, Huygen FJ et al. Is there an association between psychological factors and the Complex Regional Pain Syndrome type 1 (CRPS1) in adults? A systematic review. Pain Sep 2009; 145 (1–2) 52-59
  • 67 de Mos M, Huygen FJ, Dieleman JP et al. Medical history and the onset of complex regional pain syndrome (CRPS). Pain Oct 15 2008; 139 (02) 458-466
  • 68 Geertzen JH, de Bruijn-Kofman AT, de Bruijn HP et al. Stressful life events and psychological dysfunction in Complex Regional Pain Syndrome type I. Clin J Pain Jun 1998; 14 (02) 143-147
  • 69 Bruehl S, Husfeldt B, Lubenow TR et al. Psychological differences between reflex sympathetic dystrophy and non-RSD chronic pain patients. Pain Sep 1996; 67 (01) 107-114
  • 70 Harden RN, Bruehl S, Stanos S et al. Prospective examination of pain-related and psychological predictors of CRPS-like phenomena following total knee arthroplasty: a preliminary study. Pain Dec 2003; 106 (03) 393-400
  • 71 Bruehl S, Chung OY. Psychological and behavioral aspects of complex regional pain syndrome management. Clin J Pain Jun 2006; 22 (05) 430-437
  • 72 Oerlemans HM, Oostendorp RA, de Boo T et al. Pain and reduced mobility in complex regional pain syndrome I: outcome of a prospective randomised controlled clinical trial of adjuvant physical therapy versus occupational therapy. Pain Oct 1999; 83 (01) 77-83
  • 73 Oerlemans HM, Oostendorp RA, de Boo T et al. Adjuvant physical therapy versus occupational therapy in patients with reflex sympathetic dystrophy/complex regional pain syndrome type I. Arch Phys Med Rehabil Jan 2000; 81 (01) 49-56
  • 74 van de Meent H, Oerlemans M, Bruggeman A et al. Safety of “pain exposure” physical therapy in patients with complex regional pain syndrome type 1. Pain Jun 2011; 152 (06) 1431-1438
  • 75 McCabe CS, Haigh RC, Ring EF et al. A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1). Rheumatology (Oxford) Jan 2003; 42 (01) 97-101
  • 76 Cacchio A, De Blasis E, Necozione S et al. Mirror therapy for chronic complex regional pain syndrome type 1 and stroke. N Engl J Med Aug 6 2009; 361 (06) 634-636
  • 77 Moseley GL. Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial. Pain Mar 2004; 108 (1–2) 192-198
  • 78 Moseley GL. Graded motor imagery for pathologic pain: a randomized controlled trial. Neurology Dec 26 2006; 67 (12) 2129-2134
  • 79 de Jong JR, Vlaeyen JW, de Gelder JM et al. Pain related fear, perceived harmfulness of activities, and functional limitations in complex regional pain syndrome type I. J Pain Dec 2011; 12 (12) 1209-1218
  • 80 de Jong JR, Vlaeyen JW, Onghena P et al. Reduction of pain-related fear in complex regional pain syndrome type I: the application of graded exposure in vivo. Pain Aug 2005; 116 (03) 264-275
  • 81 Ek JW, van Gijn JC, Samwel H et al. Pain exposure physical therapy may be a safe and effective treatment for longstanding complex regional pain syndrome type 1: a case series. Clin Rehabil Dec 2009; 23 (12) 1059-1066
  • 82 Lee BH, Scharff L, Sethna NF et al. Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes. J Pediatr Jul 2002; 141 (01) 135-140
  • 83 Turner JA, Mancl L, Aaron LA. Short- and long-term efficacy of brief cognitive-behavioral therapy for patients with chronic temporomandibular disorder pain: a randomized, controlled trial. Pain Apr 2006; 121 (03) 181-194
  • 84 Christensen K, Jensen EM, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Acta Chir Scand 1982; 148 (08) 653-655
  • 85 Kalita J, Vajpayee A, Misra UK. Comparison of prednisolone with piroxicam in complex regional pain syndrome following stroke: a randomized controlled trial. QJM Feb 2006; 99 (02) 89-95
  • 86 Zuurmond WW, Langendijk PN, Bezemer PD et al. Treatment of acute reflex sympathetic dystrophy with DMSO 50% in a fatty cream. Acta Anaesthesiol Scand Mar 1996; 40 (03) 364-367
  • 87 Perez RS, Zuurmond WW, Bezemer PD et al. The treatment of complex regional pain syndrome type I with free radical scavengers: a randomized controlled study. Pain Apr 2003; 102 (03) 297-307
  • 88 Adami S, Fossaluzza V, Gatti D et al. Bisphosphonate therapy of reflex sympathetic dystrophy syndrome. Ann Rheum Dis Mar 1997; 56 (03) 201-204
  • 89 Manicourt DH, Brasseur JP, Boutsen Y et al. Role of alendronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity. Arthritis Rheum Nov 2004; 50 (11) 3690-3697
  • 90 Varenna M, Zucchi F, Ghiringhelli D et al. Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study. J Rheumatol Jun 2000; 27 (06) 1477-1483
  • 91 Robinson JN, Sandom J, Chapman PT. Efficacy of pamidronate in complex regional pain syndrome type I. Pain Med Sep 2004; 5 (03) 276-280
  • 92 van de Vusse AC, Stomp-van den Berg SG, Kessels AH et al. Randomised controlled trial of gabapentin in Complex Regional Pain Syndrome type 1 [ISRCTN84121379]. BMC Neurol Sep 29 2004; 4: 13
  • 93 Sigtermans MJ, van Hilten JJ, Bauer MC et al. Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1. Pain Oct 2009; 145 (03) 304-311
  • 94 Schwartzman RJ, Alexander GM, Grothusen JR et al. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain Dec 15 2009; 147 (1–3) 107-115
  • 95 Cordivari C, Misra VP, Catania S et al. Treatment of dystonic clenched fist with botulinum toxin. Mov Disord Sep 2001; 16 (05) 907-913
  • 96 van Hilten BJ, van de Beek WJ, Hoff JI et al. Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy. N Engl J Med Aug 31 2000; 343 (09) 625-630
  • 97 Price DD, Long S, Wilsey B et al. Analysis of peak magnitude and duration of analgesia produced by local anesthetics injected into sympathetic ganglia of complex regional pain syndrome patients. Clin J Pain Sep 1998; 14 (03) 216-226
  • 98 Kemler MA, Barendse GA, van Kleef M et al. Pain relief in complex regional pain syndrome due to spinal cord stimulation does not depend on vasodilation. Anesthesiology Jun 2000; 92 (06) 1653-1660