Handchir Mikrochir Plast Chir 2010; 42(1): 19-29
DOI: 10.1055/s-0030-1247501
Übersichtsarbeit

© Georg Thieme Verlag KG Stuttgart · New York

Medikamentöse Behandlung des CRPS

Drug Treatment of CRPSS. Rüegg1
  • 1Universitätsspital Basel, Neurologie, Basel, Schweiz
Further Information

Publication History

eingereicht 25.9.2009

akzeptiert 6.1.2010

Publication Date:
04 March 2010 (online)

Zusammenfassung

Das komplexe regionale Schmerzsyndrom (CRPS) ist gekennzeichnet durch einen charakteristischen stadienhaften Ablauf mit den Hauptsymptomen Schmerzen, trophischen und entzündlichen Veränderungen sowie Funktionseinschränkung bis -verlust. Während das letzte mit intensiver Physio- und Ergotherapie behandelt werden muss, können die ersten drei Symptome medikamentös beeinflusst werden: Hauptpfeiler der medikamentösen Therapie der neuropathischen Schmerzen sind Antidepressiva, Antiepileptika und Opioide, während die eigentlichen akuten nozizeptiven Schmerzen und die akute Entzündung auf nicht-steroidale Analgetika und Steroide ansprechen. Zusätzlich wirken auch Calcitonin und die Osteoklasten hemmenden Biphosphonate schmerzlindernd und knochenerhaltend. Der Einsatz von Sympathikolytika außerhalb von lokoregionalen Anästhesieverfahren (welche an anderer Stelle besprochen werden) ist umstritten. Allgemein gibt es im Gebiet der medikamentösen Schmerzbehandlung spezifisch des komplexen regionalen Schmerzsyndroms nur sehr geringe Evidenz; die meisten Erkenntnisse werden aus der Behandlung anderer chronischer neuropathischer Schmerzsyndrome (wie diabetische Polyneuropathie oder post-Zoster-Schmerzen) übernommen oder beruhen auf pathophysiologischen Überlegungen.

Abstract

The main symptoms of excruciating pain, trophic and inflammatory changes, as well as functional impairment of limbs are the hallmark of the complex regional pain syndrome (CRPS). While functional impairments have to be treated by physical and occupational therapy, the former three symptoms are amendable to drug treatment: antidepressants, antiepileptic drugs and opioids are the most important drug classes for alleviating neuropathic pain whereas acute nociceptive pain may be positively influenced by non-steroidal anti-inflammatory drugs and steroids. In addition, calcitonin and the biphosphonates inhibit osteoclasts and therefore loss of bone mass and may thus also reduce pain. The use of sympatholytic agents beyond locoregional anesthesia techniques (which are covered elsewhere in this issue) is not unequivocal. In general, the evidence level for treatment strategies specifically for the complex regional pain syndrome is very poor; most recommendations and algorithms rely on results derived from studies testing drugs against other conditions where chronic (neuropathic) pain is prevalent, like diabetic polyneuropathy or postherpetic neuralgia, or medications are used on the basis of pathomechanistic considerations.

Literatur

  • 1 Pappagallo M, Rosenberg AD. Epidemiology, pathophysiology, and management of complex regional pain syndrome.  Pain Pract. 2001;  1 11-20
  • 2 Beniczky S, Tajti J, Timea Varga E. et al . Evidence-based pharmacological treatment of neuropathic pain syndromes.  J Neural Trans. 2005;  112 735-749
  • 3 Littlejohn G. Regional pain syndrome: clinical characteristics, mechanisms and management.  Nat Clin Pract Rheumatol. 2007;  3 504-511
  • 4 Stanton-Hicks MD, Burton WA, Bruehl SP. et al . An updated interdisciplinary clinical pathway for CRPS: Report of an expert panel.  Pain Pract. 2002;  2 1-16
  • 5 Burton AW, Hassenbusch III SJ, Warneke C. et al . Complex regional pain syndrome (CRPS): Survey of current practices.  Pain Pract. 2004;  4 74-83
  • 6 Birklein F. Complex regional pain syndrome.  J Neurol. 2005;  252 131-138
  • 7 Li Z, Paterson Smith B, Smith TL. et al . Diagnosis and management of complex regional pain syndrome complicating upper extremity recovery.  J Hand Ther. 2005;  18 270-276
  • 8 Berthelot JM. Current management of reflex sympathetic dystrophy syndrome (complex regional pain syndrome type I).  Joint Bone Spine. 2006;  73 495-499
  • 9 Rowbotham MC. Pharmacologic management of complex regional pain syndrome.  Clin J Pain. 2006;  22 425-429
  • 10 Mackey S, Feinberg S. Pharmacologic therapies for complex regional pain syndrome.  Curr Pain Headache Rep. 2007;  11 38-43
  • 11 Eisenberg E, Geller R, Brill S. Pharmacotherapy options for complex regional pain syndrome.  Expert Rev Neurotherapeutics. 2007;  7 521-531
  • 12 Albazaz R, Wong YT, Homer-Vanniasinkam S. Complex regional pain syndrome: a review.  Ann Vasc Surg. 2008;  22 297-306
  • 13 Hsu ES. Practical management of complex regional pain syndrome.  Am J Ther. 2009;  16 147-154
  • 14 Birklein F, Schmelz M. Neuropeptides, neurogenic inflammation and complex regional pain syndrome (CRPS).  Neurosci Lett. 2008;  437 199-202
  • 15 Benemei S, Nicoletti P, Capone JG. et al . CGRP receptors in the control of pain and inflammation.  Curr Opin Phamacol. 2009;  9 9-14
  • 16 Anand P, Whiteside G, Fowler CJ. et al . Targeting CB2 receptors and the endocannabinoid system for the treatment of pain.  Brain Res Rev. 2009;  60 255-266
  • 17 Blaes F, Tschernatsch M, Braeu ME. et al . Autoimmunity in complex-regional pain syndrome.  Ann N Y Acad Sci. 2007;  1107 168-173
  • 18 Saab CY, Hains BC. Remote neuroimmune signalling: a long-range mechanism of nociceptive network plasticity.  TINS. 2009;  32 110-117
  • 19 Momin A, McNaughton PA. Regulation of firing frequency in nociceptive neurons by pro-inflammatory mediators.  Exp Brain Res. 2009;  196 45-52
  • 20 Gibbs GF, Drummond PD, Finch PM. et al . Unravelling the pathophysiology of complex regional pain syndrome: focus on sympathetically maintained pain.  Clin Exp Pharmacol Physiol. 2008;  35 717-724
  • 21 Zamponi GW, Lewis RJ, Todorovic SM. et al . Role of voltage-gated calcium channels in ascending pain pathways.  Brain Res Rev. 2009;  60 84-89
  • 22 Hans G, Schmidt BL, Strichartz G. Nociceptive sensitization by endothelin-1.  Brain Res Rev. 2009;  60 36-42
  • 23 Benarroch EE. Descending monoaminergic pain modulation. Bidirectional control and clinical revelance.  Neurology. 2008;  71 217-221
  • 24 Cervero F. Spinal cord hyperexcitability and its role in pain and hyperalgesia.  Exp Brain Res. 2009;  196 129-137
  • 25 Heinricher MM, Tavares I, Leith JL. et al . Descending control of nociception: specifity, recruitment and plasticity.  Brain Res Rev. 2009;  60 214-235
  • 26 Abbadie C, Bhangoo S, De Koninck Y. et al . Chemokines and pain mechanisms.  Brain Res Rev. 2009;  60 125-134
  • 27 Neugebauer V, Galhardo V, Maione S. et al . Forebrain pain mechanisms.  Brain Res Rev. 2009;  60 226-242
  • 28 Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes.  Pain. 1997;  73 123-139
  • 29 Forouzanfar T, Köke AJA, van Kleef M. et al . Treatment of complex regional pain syndrome type I.  Eur J Pain. 2002;  6 105-122
  • 30 Jensen TS, Madsen CS, Finnerup NB. Pharmacology and treatment of neuropathic pains.  Curr Opin Neurol. 2009;  22 epub ahead of print Sept 9
  • 31 Appelboom T. Calcitonin in reflex sympathetic dystrophy syndrome and other painful conditions.  Bone. 2002;  30 (S 05) S84-S86
  • 32 Yanow J, Pappagallo M, Pillai L. Complex regional pain syndrome (CRPS/RSD) and neuropathic pain: role of intravenous biphosphonates as analgesics.  ScientificWorldJournal. 2008;  8 229-236
  • 33 Maihöfner C, Birklein F. Complex regional pain syndrome: new aspects on pathophysiology and treatment (Article in German).  Fortschr Neurol Psychiatr. 2007;  75 331-342
  • 34 Pal M, Angaru S, Kodimuthali A. et al . Vanilloid receptor antagonists: emerging class of novel anti-inflammatory agents for pain management.  Curr Pharm Des. 2009;  15 1008-1026
  • 35 Wallace MS, Ridgeway BM, Leung AY. et al . Concentration-effect relationship of intravenous lidocaine on the allodynia of complex regional pain syndrome types I and II.  Anesthesiology. 2000;  92 75-83
  • 36 Wörz R, Wörz E. Long-term treatment of chronic pain with tilidine-naloxone. An analysis of 50 patients with chronic pain conditions of non-malignant origin.  Fortschr Med. 1995;  113 388-392 (Article in German)
  • 37 Nicholson B. Benefits of extended-release opioid analgesic formulations in the treatment of cahronic pain.  Pain Pract. 2009;  9 71-81
  • 38 Norrbrink C, Lundeberg T. Tramadol in neuropathic pain after spinal cord injury: a rndomized, double-blind, placebo-controlled trial.  Clin J Pain. 2009;  25 177-184
  • 39 Grond S, Sablotzki A. Clinical pharmacology of tramadol.  Clin Pharmacokinet. 2004;  43 879-923
  • 40 Sinis N, Birbaumer N, Gustin S. et al . Memantine treatment of complex regional pain syndrome: a preliminary report of six cases.  Clin J Pain. 2007;  23 237-243
  • 41 Moore RA, Straube S, wiffen PJ. et al . Pregabalin for acute and chronic pain in adults.  Cochrane Database of Systematic Reviews. 2009;  Issue 3 Art. No.: CD007076. DOI: 10.1002/14651858.CD007076.pub2.
  • 42 Mizoguchi H, Watanabe C, Yonezawa A. et al . New therapy for neuropathic pain.  Int Rev Neurobiol. 2009;  85 249-260
  • 43 Zin CS, Nissen LM, Smith MT. et al . An update on the pharmacological management of post-herpetic neuralgia and painful diabetic polyneuropathy.  CNS Drugs. 2008;  22 417-442
  • 44 Yalcin I, Choucair-Jaafar N, Benbouzid M. et al . β2-adrenoreceptors are critical for antidepressant treatment of neuropathic pain.  Ann Neurol. 2009;  65 218-225
  • 45 Dick IE, Brochu RM, Purohit Y. et al . Sodium channel blockade may contribute to the analgesic efficacy of antidepressants.  J Pain. 2007;  8 315-324
  • 46 Saarto Z, Wiffen SJ. Antidepressants for neuropathic pain.  Cochrane Database of Systematic Reviews. 2007;  (Issue 4.) Art.Nr.: CD005454.DOI: 10.1002/14651858.CD005454.pub2
  • 47 Grothe DR, Scheckner B, Albano D. Treatment of pain syndromes with venlafaxine.  Pharmacotherapy. 2004;  24 621-629
  • 48 Sultan A, Gaskell H, Derry S. et al . Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomized trials.
  • 49 Slonimski M, Abram SE, Zuniga RE. Intrathecal baclofen in pain management.  Reg Anesth Pain Med. 2004;  29 269-276
  • 50 Rauck RL, Eisenach JC, Jackson K. et al . Epidural clonidine treatment for refractory reflex sympathetic dystrophy.  Anesthesiology. 1993;  79 1163-1169
  • 51 Ranoux D, Attal N, Morain F. et al . Botulinum toxin A induces direct analgesic effects in chronic neuropathic pain.  Ann Neurol. 2008;  64 274-283
  • 52 Carroll I, Clark JD, Mackey S. Sympathetic block with botulinum toxin to treat complex regional pain syndrome.  Ann Neurol. 2009;  65 348-351
  • 53 Munts AG, van der Plas AA, Vormoolen JH. et al . Intrathecal glycine for pain and dystonia in complex regional pain syndrome.  Pain. 2009;  epub ahead of print August 13.
  • 54 Sheets PL, Heers C, Stoehr T. et al . Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine.  J Pharmacol Exp Ther. 2008;  326 89-99
  • 55 Daly AE, Bialocerkowski AE. Does evidence support physiotherapy management of adult complex regional pain syndrome type one?.  A systematic review. Eur J Pain. 2009;  13 339-353
  • 56 Bruehl S, Chung OY. Psychological and behavioural aspects of complex regional pain syndrome.  Clin J Pain. 2006;  22 430-437
  • 57 Kalita J, Vajpayee A, Misra UK. Comparison of prednisolone with piroxicam in complex regional pain syndrome following stroke: a randomized controlled trial.  QJM. 2006;  99 89-95
  • 58 Perrigot M, Bergego C, Hocini A. et al . Algodystrophy sindrome in emiplegia. Clinical and therapeutic study (article in French).  Ann Med Interne. 1982;  133 544-548
  • 59 Gallien P, Nicolas B, Robineau S. et al . The reflex sympathetic dystrophy syndrome in patients who have had a spinal cord injury.  Paraplegia. 1995;  33 715-720
  • 60 Sullivan M. Integrated treatment of a women with chronic hand pain.  Hosp Comm Psychiatry. 1991;  42 474-475
  • 61 Harke H, Gretenkort P, Ladleif HU. et al . The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained release morphine in patients pretreated with spinal cord stimulation: a double-blind randomized study.  Anesth Analg. 2001;  92 488-495
  • 62 van de Vusse AC, Stomp-van den Berg SG, Kessels AH. et al . Randomised controlled trial of gabapentin in complex regio5nal pain syndrome type 1 (ISRCTN84121379).  BMC Neurol. 2004;  Sep 29; 4 13-1
  • 63 Serpell MG. Neuropathic pain study group . Gabapentin in neuropathic pain syndromes: a randomised, double-blind, placebo controlled trial.  Pain. 2002;  99 557-566
  • 64 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. 2009;  145 304-311
  • 65 Sigtermans M, Noppers I, Sarton E. et al . An observational study on the effect of S(+)-ketamine on chronic pain versus experimental acute pain in complex regional pain syndrome type 1 patients.  Eur J Pain. 2009;  epub ahead of print June 17
  • 66 Kiefer RT, Rohr P, Ploppa Dietrich HJ. et al . Efficacy of ketamine in anesthetic dosage for the treatment of refractory complex regional pain syndrome: an open-label phase II study.  Pain Med. 2008;  9 1173-1201
  • 67 Correll GE, Maleki J, Gracely EJ. et al . Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome.  Pain Med. 2004;  5 263-275
  • 68 Goldberg ME, Domsky R, Scaringe D. et al . Multi-day low dose ketamine infusion for the treatment of complex regional pain syndrome.  Pain Physician. 2005;  8 175-179
  • 69 Finch PM, Knudsen L, Drummond PD. Reduction of allodynia in patients with complex regional pain syndrome: a double-blind placebo-controlled trial of topical ketamine. Pain 2009: epub ahead August 22
  • 70 Kiefer RT, Rohr PA, Nohé B. et al . A pilot open-label study of the efficacy of subanesthetic isomeric S(+)-ketamine in refractory CRPS patients.  Pain Med. 2008;  9 44-54
  • 71 Sinis N, Birbaumer N, Schwarz A. et al . Memenatine und komplexes regionales Schmerzsyndrom (CRPS): Behandlungseffekte und kortikale Reorganisation.  Handchir Mikrochir Plast Chir. 2006;  38 164-171
  • 72 Eiche J, Krimmer H, Lanz U. et al . Treatment of hand surgery patients in chronic pain (Article in German)].  Orthopäde. 2003;  32 413-417
  • 73 Agrawal S, Polydefkis M, Block B. et al . Transdermal fentanyl reduces pain and improves functional activity in neuropathic pain states.  Pain Med. 2007;  8 554-562
  • 74 Simpson DM, Messina J, Xie F. et al . Fentanyl buccal tablet for relief of breakthrough pain in opioid-tolerant adult patinets with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study.  Clin Ther. 2007;  29 588-601
  • 75 Moulin DE, Palma D, Watling C. et al . Methadone in the management of intractable neuropathic noncancer pain.  Can J Neurol Sci. 2005;  32 340-343
  • 76 Christensen K, Jensen EM, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids.  Acta Chir Scand. 1982;  148 653-655
  • 77 Braus DF, Krauss JK, Strobel J. The shoulder-hand syndrome after stroke: prospective clinical trial.  Ann Neurol. 1994;  36 728-733
  • 78 Bianchi C, Rossi S, Turi S. et al . Long-term functional outcome measures in corticosteroid-treated complex regional pain syndrome.  Eura Medicophys. 2006;  42 103-111
  • 79 Inchiosa Jr MA, Kizelshteyn G. Treatment of complex regional pain syndrome type I with oral phenoxybenzamine: rationale and case reports.  Pain Pract. 2008;  8 125-132
  • 80 Gobelet C, Waldburger M, Meier JL. The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy.  Pain. 1992;  48 171-175
  • 81 Bickerstaff DR, Kanis JA. The use of nasal calcitonin in the treatment of posttraumatic algodystrophy.  Br J Rheumatol. 1991;  30 291-294
  • 82 Perez RS, Kwakkel G, Zuurmons WW. et al . Treatment of reflex sympathetic dystrophy (CRPS type I): a research synthesis of 21 randomized clinical trials.  J Pain Symptom Manage. 2001;  21 511-526
  • 83 Sahin F, Yilmaz F, Kotevoglu N. et al . Efficacy of salmon calcitonin in complex regional pain syndrome (type I) in addition to physical therapy.  Clin Rheumatol. 2006;  25 143-148
  • 84 Brunner F, Schmid A, Kissling R. et al . Biphosphonates for the therapy of complex regional pain syndrome I – systematic review.  Eur J Pain. 2009;  13 17-21
  • 85 Manicourt DH, Brasseur JP, Boutsen Y. et al . Role of elndronate in therapy for posttraumatic complex regional pain syndrome type I of the lower extremity.  Arthritis Rheum. 2004;  50 3690-3697
  • 86 Adami S, Fossaluzza V, Gatti D. et al . Biphosphonate therapy of reflex sympathetic dystrophy sindrome.  Ann Rheum Dis. 1997;  56 201-204
  • 87 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. 2000;  27 1477-1483
  • 88 Breuer B, Pappagallo M, Ongseng F. et al . An open-lanbel pilot trial of ibandronate for complex regional pain syndrome.  Clin J Pain. 2008;  24 685-689
  • 89 Robinson JN, Sandom J, Chapman PT. Efficacy of pamidronate in complex regional pain syndrome type I.  Pain Med. 2004;  5 276-280
  • 90 Zuniga RE, Perera S, Abram SE. Intrathecal baclofen:a useful agent in the treatment of well-established complex regional pain syndrome.  Reg Anesth Pain Med. 2002;  27 90-93
  • 91 Van Rijn MA, Munts AG, Marinus J. et al . Intrathecal baclofen for dystonia of complex regional pain syndrome.  Pain. 2009;  143 41-47
  • 92 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. 2000;  343 625-630
  • 93 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. 2003;  102 297-307
  • 94 Ribbers GM, Stam HJ. Complex regional pain syndrome type I treated with topical capsaicin: a case report.  Arch Phys Med Rehabil. 2001;  82 851-852
  • 95 Zuurmond WW, Langendijck PN, Bezemer PD. et al . Treatment of acute reflex sympathetic dystrophy with DMSO 50% in a fatty cream.  Acta Anaesthesiol Scand. 1996;  40 364-367
  • 96 Rajkumar SV, Fonseca R, Witzig TE. Complete resolution of reflex sympathetic dystrophy with thalidomide treatment.  Arch Intern Med. 2001;  161 2502-2503
  • 97 Bernateck M, Rolke R, Birklein F. et al . Successful intravenous regional block with low-dose tumor necrosis factor-α antibody infliximab for treatment of complex regional pain syndrome 1.  Anesth Analg. 2007;  105 1148-1151
  • 98 French J, Gronseth G. Invited article: lost in a jungle of evidence – we need a compass.  Neurology. 2008;  71 1634-1638

Korrespondenzadresse

PD Stephan Rüegg

Universitätsspital Basel

Neurologie

Petersgraben 4

4031 Basel

Schweiz

Email: srueegg@uhbs.ch