Komplex regionale Schmerzsyndrome: Neues zu Pathophysiologie und Therapie

Zusammenfassung

Die Komplex-Regionalen Schmerzsyndrome (complex regional pain syndrome; CRPS) wurden früher als Morbus Sudeck oder Kausalgie bezeichnet. Sie sind Sonderformen neuropathischer Schmerzsyndrome. Ein CRPS kann sich als Komplikation nach Frakturen und Verletzungen der Extremitäten, aber auch nach Nerven- oder ZNS-Läsionen entwickeln. Selten tritt ein CRPS spontan auf. Als klinisches Bild findet sich eine relativ charakteristische Trias, die autonome (u. a. Hauttemperaturstörungen, Hautverfärbungen, Schwitzstörungen), sensorische (Schmerz und Hyperalgesie) und motorische (Paresen, Tremor, Dystonie) Störungen umfasst. Die Diagnose wird in erster Linie anhand klinischer Merkmale gestellt, apparative Zusatzuntersuchungen können die Diagnose aber unterstützen. Pathophysiologisch werden eine gesteigerte neurogene Entzündung, eine pathologische sympathiko-afferente Kopplung und in jüngster Zeit auch neuroplastische Veränderungen im ZNS diskutiert. Daneben mehren sich Anhaltspunkte für eine genetische Disposition. Die Therapie des CRPS ist multidisziplinär. Zu den nicht-medikamentösen Therapiekonzepten zählen insbesondere Physio/Ergotherapie, physikalische Maßnahmen und die transkutane elektrische Nervenstimulation. Medikamentöse Therapien orientieren sich an der individuellen Symptomkonstellation und umfassen Glukokortikoide, Radikalfänger, die Pharmakotherapie der neuropathischen Schmerzen, und Substanzen, die in den Knochenstoffwechsel eingreifen (Calcitonin und Biphosphonate). Sympathikusblockaden können bei Vorliegen eines sympathisch-unterhaltenen Schmerzsyndroms eingesetzt werden. Zu den invasiven Maßnahmen zählt vor allem die rückenmarksnahe Elektrostimulation („spinal cord stimulator”). Diese Arbeit stellt neue Aspekte von Pathophysiologie und Therapie des CRPS vor.

Abstract

Complex-regional pain syndromes (CRPS), formerly known as Sudeck's dystrophy and causalgia, belong to the neuropathic pain syndromes. CRPS may develop following fractures, limb trauma or lesions of the peripheral or central (CNS) nervous system. Occasionally, CRPS may also develop spontaneously. The clinical picture comprises a characteristic clinical triade of symptoms including autonomic (disturbances of skin temperature, colour, presence of sweating abnormalities), sensory (pain and hyperalgesia) and motor (paresis, tremor, dystonia) disturbances. Diagnosis is mainly based on clinical signs. However, additional laboratory, neurophysiological and radiological examinations may help to corroborate correct diagnosis. Several pathophysiological concepts have been proposed to explain the complex symptoms of CRPS: 1, facilitated neurogenic inflammation; 2, pathological sympatho-afferent coupling; 3, neuroplastic changes within the CNS. Furthermore, there is accumulating evidence that genetic factors may predispose for CRPS. Therapy is based on a multidisciplinary approach. Non-pharmacological approaches include physiotherapy and occupational therapy. Pharmacotherapy is based on individual symptoms and includes steroids, free radical scavengers, treatment of neuropathic pain, and finally agents interfering with bone metabolism (calcitonin, biphosphonates). Sympathetic blocks are useful for the treatment of sympathetically maintained pain. Invasive therapeutic concepts include implantation of spinal cord stimulators. This review covers new aspects of pathophysiology and therapy of CRPS.

Schlüsselwörter

Komplex regionales Schmerzsyndrom - CRPS - Morbus Sudeck - Kausalgie - neuropathischer Schmerz - sympathische Reflexdystrophie - sympathisch unterhaltener Schmerz - Therapie

Key words

complex regional pain syndrome - CRPS - Sudeck's dystrophy - reflex sympathetic dystrophy - causalgia - neuropathic pain - sympathetically maintained pain - therapy

Literatur

• 1 Mitchell S W, Morehouse G R, Keen W W. Gunshot wounds and other injuries of nerves. New York: Lippincott JP 1864
• 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 Livingston W K. Pain mechanisms. A physiologic interpretation of causalgia and its related states. New York: Macmillan 1944
• 4 Doupe J, Cullen C R, Chance G R. Post-traumatic pain and the causalgic syndromes.  J Neurol Neurosurg Psychiatry. 1944;  7 33-48
• 5 Evans J A. Reflex sympathetic dystrophy.  Surg Clin North Am. 1946;  26 435-448
• 6 Sudeck P. Über die akute entzündliche Knochenatrophie.  Arch Klin Chir. 1900;  62 147-156
• 7 Sudeck P. Die so genannte akute Knochenatrophie als Entzündungsvorgang.  Der Chirurg. 1942;  15 449-457
• 8 Stanton-Hicks M, Jänig W, Hassenbusch S, Haddox J D, Boas R, Wilson P. Reflex sympathetic dystrophy: changing concepts and taxonomy.  Pain. 1995;  63 (1) 127-133
• 9 Sandroni P, Benrud-Larson L M, McClelland R L, Low P A. Complex regional pain syndrome type I: incidence and prevalence in Olmsted county, a population-based study.  Pain. 2003;  103 (1 - 2) 199-207
• 10 Dijkstra P U, Groothoff J W, ten Duis H J, Geertzen J H. Incidence of complex regional pain syndrome type I after fractures of the distal radius.  Eur J Pain. 2003;  7 (5) 457-462
• 11 Atkins R M, Duckworth T, Kanis J A. Algodystrophy following Colles' fracture.  J Hand Surg [Br ]. 1989;  14 (2) 161-164
• 12 Field J, Atkins R M. Algodystrophy is an early complication of Colles' fracture. What are the implications?.  J Hand Surg [Br ]. 1997;  22 (2) 178-182
• 13 Sarangi P P, Ward A J, Smith E J, Staddon G E, Atkins R M. Algodystrophy and osteoporosis after tibial fractures.  J Bone Joint Surg Br. 1993;  75 (3) 450-452
• 14 Bickerstaff D R, Kanis J A. Algodystrophy: an under-recognized complication of minor trauma.  Br J Rheumatol. 1994;  33 (3) 240-248
• 15 Raja S N, Grabow T S. Complex regional pain syndrome I (reflex sympathetic dystrophy).  Anesthesiology. 2002;  96 (5) 1254-1260
• 16 Veldman P H, Reynen H M, Arntz I E, Goris R J. Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients.  Lancet. 1993;  342 (8878) 1012-1016
• 17 Birklein F, Riedl B, Sieweke N, Weber M, Neundörfer B. Neurological findings in complex regional pain syndromes - analysis of 145 cases.  Acta Neurol Scand. 2000;  101 (4) 262-269
• 18 Allen G, Galer B S, Schwartz L. Epidemiology of complex regional pain syndrome: a retrospective chart review of 134 patients.  Pain. 1999;  80 (3) 539-544
• 19 Geertzen J H, Bruijn-Kofman A T, de Bruijn H P, Wiel H B van de, Dijkstra P U. Stressful life events and psychological dysfunction in Complex Regional Pain Syndrome type I.  Clin J Pain. 1998;  14 (2) 143-147
• 20 Lynch M E. Psychological aspects of reflex sympathetic dystrophy: a review of the adult and paediatric literature.  Pain. 1992;  49 (3) 337-347
• 21 Laan L  van der, Spaendonck  K van, Horstink M W, Goris R J. The Symptom Checklist-90 Revised questionnaire: no psychological profiles in complex regional pain syndrome-dystonia.  J Pain Symptom Manage. 1999;  17 (5) 357-362
• 22 Harden R N. et al . Prospective examination of pain-related and psychological predictors of CRPS-like phenomena following total knee arthroplasty: a preliminary study.  Pain. 2003;  106 (3) 393-400
• 23 Birklein F, Riedl B, Claus D, Neundörfer B. Pattern of autonomic dysfunction in time course of complex regional pain syndrome.  Clin Auton Res. 1998;  8 (2) 79-85
• 24 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 (Pt 3) 587-599
• 25 Wasner G, Schattschneider J, Baron R. Skin temperature side differences - a diagnostic tool for CRPS?.  Pain. 2002;  98 (1 - 2) 19-26
• 26 Birklein F, Sittl R, Spitzer A, Claus D, Neundörfer B, Handwerker H O. Sudomotor function in sympathetic reflex dystrophy.  Pain. 1997;  69 (1 - 2) 49-54
• 27 Geertzen J H, Dijkstra P U, Groothoff J W, ten Duis H J, Eisma W H. Reflex sympathetic dystrophy of the upper extremity - a 5.5-year follow-up. Part I. Impairments and perceived disability.  Acta Orthop Scand Suppl. 1998;  279 12-18
• 28 Maihöfner C, Handwerker H O, Neundörfer B, Birklein F. Patterns of cortical reorganization in Complex Regional Pain Syndrome.  Neurology. 2003;  61 (2) 1707-1715
• 29 Maihöfner C, Forster C, Birklein F, Neundörfer B, Handwerker H O. Brain processing during mechanical hyperalgesia in complex regional pain syndrome: a functional MRI study.  Pain. 2005;  114 (1 - 2) 93-103
• 30 Sieweke N, Birklein F, Riedl B, Neundörfer B, Handwerker H O. Patterns of hyperalgesia in complex regional pain syndrome.  Pain. 1999;  80 (1 - 2) 171-177
• 31 Galer B S, Butler S, Jensen M P. Case reports and hypothesis: a neglect-like syndrome may be responsible for the motor disturbance in reflex sympathetic dystrophy (Complex Regional Pain Syndrome-1).  J Pain Symptom Manage. 1995;  10 (5) 385-391
• 32 Galer B S, Jensen M. Neglect-like symptoms in complex regional pain syndrome: results of a self-administered survey.  J Pain Symptom Manage. 1999;  18 (3) 213-217
• 33 Förderreuther S, Sailer U, Straube A. Impaired self-perception of the hand in complex regional pain syndrome (CRPS).  Pain. 2004;  110 (3) 756-761
• 34 Deuschl G, Blumberg H, Lücking C H. Tremor in reflex sympathetic dystrophy.  Arch Neurol. 1991;  48 (12) 1247-1252
• 35 Schwartzman R J, Kerrigan J. The movement disorder of reflex sympathetic dystrophy.  Neurology. 1990;  40 (1) 57-61
• 36 Hilten B J van, Beek W J van de, Hoff J I, Voormolen J H, Delhaas E M. Intrathecal baclofen for the treatment of dystonia in patients with reflex sympathetic dystrophy.  N Engl J Med. 2000;  343 (9) 625-630
• 37 Hilten J J van, Beek W J van de, Roep B O. Multifocal or generalized tonic dystonia of complex regional pain syndrome: a distinct clinical entity associated with HLA-DR13.  Ann Neurol. 2000;  48 (1) 113-116
• 38 Ribbers G M, Oosterhuis W P, Limbeek J van, de Metz M. Reflex sympathetic dystrophy: is the immune system involved?.  Arch Phys Med Rehabil. 1998;  79 (12) 1549-1552
• 39 Beek W J van de, Remarque E J, Westendorp R G, Hilten J J van. Innate cytokine profile in patients with complex regional pain syndrome is normal.  Pain. 2001;  91 (3) 259-261
• 40 Herbert M K, Holzer P. Neurogenic inflammation. I. Basic mechanisms, physiology and pharmacology.  Anasthesiol Intensivmed Notfallmed Schmerzther. 2002;  37 (6) 314-325
• 41 Schmidt R, Schmelz M, Forster C, Ringkamp M, Torebjork E, Handwerker H. Novel classes of responsive and unresponsive C nociceptors in human skin.  J Neurosci. 1995;  15 (1) 333-341
• 42 Weidner C, Schmelz M, Schmidt R, Hansson B, Handwerker H O, Torebjork H E. Functional attributes discriminating mechano-insensitive and mechano-responsive C nociceptors in human skin.  J Neurosci. 1999;  19 (22) 10 184-10 190
• 43 Schmelz M, Michael K, Weidner C, Schmidt R, Torebjork H E, Handwerker H O. Which nerve fibers mediate the axon reflex flare in human skin?.  Neuroreport. 2000;  11 (3) 645-648
• 44 Schmelz M, Schmidt R, Weidner C, Hilliges M, Torebjork H E, Handwerker H O. Chemical response pattern of different classes of C-nociceptors to pruritogens and algogens.  J Neurophysiol. 2003;  89 (5) 2441-2448
• 45 Klede M, Handwerker H O, Schmelz M. Central origin of secondary mechanical hyperalgesia.  J Neurophysiol. 2003;  90 (1) 353-359
• 46 Ziegler E A, Magerl W, Meyer R A, Treede R D. Secondary hyperalgesia to punctate mechanical stimuli. Central sensitization to A-fibre nociceptor input.  Brain. 1999;  122 (Pt 12) 2245-2257
• 47 Weber M, Birklein F, Neundörfer B, Schmelz M. Facilitated neurogenic inflammation in complex regional pain syndrome.  Pain. 2001;  91 (3) 251-257
• 48 Leis S, Weber M, Schmelz M, Birklein F. Facilitated neurogenic inflammation in unaffected limbs of patients with complex regional pain syndrome.  Neurosci Lett. 2004;  359 (3) 163-166
• 49 Birklein F, Schmelz M, Schifter S, Weber M. The important role of neuropeptides in complex regional pain syndrome.  Neurology. 2001;  57 (12) 2179-2184
• 50 Huygen F J, De Bruijn A G, de Bruin M T, Groeneweg J G, Klein J, Zijistra F J. Evidence for local inflammation in complex regional pain syndrome type 1.  Mediators Inflamm. 2002;  11 (1) 47-51
• 51 Opree A, Kress M. Involvement of the proinflammatory cytokines tumor necrosis factor-α, IL-1 β, 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. 2000;  20 (16) 6289-6293
• 52 Maihöfner C, Handwerker H O, Neundörfer B, Birklein F. Mechanical hyperalgesia in complex regional pain syndrome: a role for TNF-α?.  Neurology. 2005;  65 (2) 311-313
• 53 Huygen F J, Niehof S, Zijlstra F J, Hagen P M van, Daele P L van. Successful treatment of CRPS 1 with anti-TNF.  J Pain Symptom Manage. 2004;  27 (2) 101-103
• 54 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 (5) 613-620
• 55 Birklein F, Riedl B, Neundörfer B, Handwerker H O. Sympathetic vasoconstrictor reflex pattern in patients with complex regional pain syndrome.  Pain. 1998;  75 (1) 93-100
• 56 Baron R, Schattschneider J, Binder A, Siebrecht D, Wasner G. Relation between sympathetic vasoconstrictor activity and pain and hyperalgesia in complex regional pain syndromes: a case-control study.  Lancet. 2002;  359 (9318) 1655-1660
• 57 Jänig W, Baron R. Complex regional pain syndrome is a disease of the central nervous system.  Clin Auton Res. 2002;  12 (3) 150-164
• 58 Drummond P D, Skipworth S, Finch P M. α1-adrenoceptors in normal and hyperalgesic human skin.  Clin Sci (Lond). 1996;  91 (1) 73-77
• 59 Sato J, Perl E R. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury.  Science. 1991;  251 (5001) 1608-1610
• 60 Torebjork E, Wahren L, Wallin G, Hallin R, Koltzenburg M. Noradrenaline-evoked pain in neuralgia.  Pain. 1995;  63 (1) 11-20
• 61 Walker A E, Nulsen F. Electrical stimulation of the upper thoracic portion of the sympathetic chain in man.  Arch Neurol Psychiatr. 1948;  59 559-560
• 62 Kurvers H A. et al . Reflex sympathetic dystrophy: evolution of microcirculatory disturbances in time.  Pain. 1995;  60 (3) 333-340
• 63 Koban M, Leis S, Schultze-Mosgau S, Birklein F. Tissue hypoxia in complex regional pain syndrome.  Pain. 2003;  104 (1 - 2) 149-157
• 64 Birklein F, Weber M, Ernst M, Riedl B, Neundörfer B, Handwerker H O. Experimental tissue acidosis leads to increased pain in complex regional pain syndrome (CRPS).  Pain. 2000;  87 (2) 227-234
• 65 Miao F J, Jänig W, Levine J. Role of sympathetic postganglionic neurons in synovial plasma extravasation induced by bradykinin.  J Neurophysiol. 1996;  75 (2) 715-724
• 66 Drummond P D, Finch P M, Edvinsson L, Goadsby P J. Plasma neuropeptide Y in the symptomatic limb of patients with causalgic pain.  Clin Auton Res. 1994;  4 (3) 113-116
• 67 Rommel O, Malin J P, Zenz M, Jänig W. Quantitative sensory testing, neurophysiological and psychological examination in patients with complex regional pain syndrome and hemisensory deficits.  Pain. 2001;  93 (3) 279-293
• 68 Rommel O. et al . Hemisensory impairment in patients with complex regional pain syndrome.  Pain. 1999;  80 (1 - 2) 95-101
• 69 Maihöfner C, Handwerker H O, Neundörfer B, Birklein F. Cortical reorganization during recovery from complex regional pain syndrome.  Neurology. 2004;  63 (4) 693-701
• 70 Pleger B. et al . Mean sustained pain levels are linked to hemispherical side-to-side differences of primary somatosensory cortex in the complex regional pain syndrome I.  Exp Brain Res. 2004;  155 (1) 115-119
• 71 Pleger B. et al . Sensorimotor retuning in complex regional pain syndrome parallels pain reduction.  Ann Neurol. 2005;  57 (3) 425-429
• 72 Flor H. et al . Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.  Nature. 1995;  375 (6531) 482-484
• 73 Leis S, Weber M, Isselmann A, Schmelz M, Birklein F. Substance-P-induced protein extravasation is bilaterally increased in complex regional pain syndrome.  Exp Neurol. 2003;  183 (1) 197-204
• 74 Hühne K, Leis S, Schmelz M, Rautenstrauss B, Birklein F. A polymorphic locus in the intron 16 of the human angiotensin-converting enzyme (ACE) gene is not correlated with complex regional pain syndrome I (CRPS I).  Eur J Pain. 2004;  8 (3) 221-225
• 75 Beek W J van de, Roep B O, Slik A R van der, Giphart M J, Hilten B J van. Susceptibility loci for complex regional pain syndrome.  Pain. 2003;  103 (1 - 2) 93-97
• 76 Graif M, Schweitzer M E, Marks B, Matteucci T, Mandel S. Synovial effusion in reflex sympathetic dystrophy: an additional sign for diagnosis and staging.  Skeletal Radiol. 1998;  27 (5) 262-265
• 77 Zyluk A. The usefulness of quantitative evaluation of three-phase scintigraphy in the diagnosis of post-traumatic reflex sympathetic dystrophy.  J Hand Surg [Br]. 1999;  24 (1) 16-21
• 78 Kozin F, Soin J S, Ryan L M, Carrera G F, Wortmann R L. Bone scintigraphy in the reflex sympathetic dystrophy syndrome.  Radiology. 1981;  138 (2) 437-443
• 79 Chelimsky T C, Low P A, Naessens J M, Wilson P R, Amadio P C, O'Brian P C. Value of autonomic testing in reflex sympathetic dystrophy.  Mayo Clin Proc. 1995;  70 (11) 1029-1040
• 80 Bruehl S, Lubenow T R, Nath H, Ivankovich O. Validation of thermography in the diagnosis of reflex sympathetic dystrophy.  Clin J Pain. 1996;  12 (4) 316-325
• 81 Stanton-Hicks M. et al . Complex Regional Pain Syndromes: guidelines for therapy.  Clin J Pain. 1998;  14 (2) 155-166
• 82 Oerlemans H M, Oostendorp R A, de Boo T, Goris R J. 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. 1999;  83 (1) 77-83
• 83 Ramachandran V S, Hirstein W. The perception of phantom limbs. The D. O. Hebb lecture.  Brain. 1998;  121 (9) 1603-1630
• 84 Pomeroy V M, Clark C A, Miller J S, Baron J C, Markus H S, Tallis R C. The potential for utilizing the “mirror neurone system” to enhance recovery of the severely affected upper limb early after stroke: a review and hypothesis.  Neurorehabil Neural Repair. 2005;  19 (1) 4-13
• 85 McCabe C S, Haigh R C, Ring E F, Halligan P W, Wall P D, Blake D R. A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1).  Rheumatology (Oxford). 2003;  42 (1) 97-101
• 86 Moseley G L. Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial.  Pain. 2004;  108 (1 - 2) 192-198
• 87 Robaina F J, Rodriguez J L, de Vera J A, Martin M A. Transcutaneous electrical nerve stimulation and spinal cord stimulation for pain relief in reflex sympathetic dystrophy.  Stereotact Funct Neurosurg. 1989;  52 (1) 53-62
• 88 Christensen K, Jensen E M, Noer I. The reflex dystrophy syndrome response to treatment with systemic corticosteroids.  Acta Chir Scand. 1982;  148 (8) 653-655
• 89 Braus D F, Krauss J K, Strobel J. The shoulder-hand syndrome after stroke: a prospective clinical trial.  Ann Neurol. 1994;  36 (5) 728-733
• 90 Kingery W S, Guo T, Agashe G S, Davies M F, Clark J D, Maze M. Glucocorticoid inhibition of neuropathic limb edema and cutaneous neurogenic extravasation.  Brain Res. 2001;  913 (2) 140-148
• 91 Kingery W S, Agashe G S, Sawamura S, Davies M F, Clark J D, Maze M. Glucocorticoid inhibition of neuropathic hyperalgesia and spinal Fos expression.  Anesth Analg. 2001;  92 (2) 476-482
• 92 Guo T Z, Wei T, Kingery W S. Glucocorticoid inhibition of vascular abnormalities in a tibia fracture rat model of complex regional pain syndrome type I. Pain 2006
• 93 Piedimonte G, McDonald D M, Nadel J A. Neutral endopeptidase and kininase II mediate glucocorticoid inhibition of neurogenic inflammation in the rat trachea.  J Clin Invest. 1991;  88 (1) 40-44
• 94 Zuurmond W W, Langendijk P N, Bezemer P D, Brink H E, de Lange J J, Loenen A C van. Treatment of acute reflex sympathetic dystrophy with DMSO 50 % in a fatty cream.  Acta Anaesthesiol Scand. 1996;  40 (3) 364-367
• 95 Zollinger P E, Tuinebreijer W E, Kreis R W, Breederveld R S. Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial.  Lancet. 1999;  354 (9195) 2025-2028
• 96 Perez R S. et al . The treatment of complex regional pain syndrome type I with free radical scavengers: a randomized controlled study.  Pain. 2003;  102 (3) 297-307
• 97 Cepeda M S, Lau J, Carr D B. Defining the therapeutic role of local anesthetic sympathetic blockade in complex regional pain syndrome: a narrative and systematic review.  Clin J Pain. 2002;  18 (4) 216-233
• 98 Price D D, Long S, Wilsey B, Rafii A. 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. 1998;  14 (3) 216-226
• 99 Tran K M, Frank S M, Raja S N, El Rahmany H K, Kim L J, Vu B. Lumbar sympathetic block for sympathetically maintained pain: changes in cutaneous temperatures and pain perception.  Anesth Analg. 2000;  90 (6) 1396-1401
• 100 Jadad A R, Carroll D, Glynn C J, McQuay H J. Intravenous regional sympathetic blockade for pain relief in reflex sympathetic dystrophy: a systematic review and a randomized, double-blind crossover study.  J Pain Symptom Manage. 1995;  10 (1) 13-20
• 101 Treede R D, Davis K D, Campbell J N, Raja S N. The plasticity of cutaneous hyperalgesia during sympathetic ganglion blockade in patients with neuropathic pain.  Brain. 1992;  115 (Pt 2) 607-621
• 102 Kingery W S. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes.  Pain. 1997;  73 (2) 123-139
• 103 Sindrup S H, Jensen T S. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action.  Pain. 1999;  83 (3) 389-400
• 104 Jensen T S. Anticonvulsants in neuropathic pain: rationale and clinical evidence.  Eur J Pain. 2002;  6 Suppl A 61 - 8 61-68
• 105 Max M B. Treatment of post-herpetic neuralgia: antidepressants.  Ann Neurol. 1994;  35 Suppl S50-S53
• 106 Sindrup S H, Bach F W, Madsen C, Gram L F, Jensen T S. Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial.  Neurology. 2003;  60 (8) 1284-1289
• 107 Mellick L B, Mellick G A. Successful treatment of reflex sympathetic dystrophy with gabapentin.  Am J Emerg Med. 1995;  13 (1) 96
• 108 Sabatowski R. et al . Pregabalin reduces pain and improves sleep and mood disturbances in patients with post-herpetic neuralgia: results of a randomised, placebo-controlled clinical trial.  Pain. 2004;  109 (1 - 2) 26-35
• 109 Rowbotham M C, Twilling L, Davies P S, Reisner L, Taylor K, Mohr D. Oral opioid therapy for chronic peripheral and central neuropathic pain.  N Engl J Med. 2003;  348 (13) 1223-1232
• 110 Watson C P, Babul N. Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia.  Neurology. 1998;  50 (6) 1837-1841
• 111 Gennari C. Analgesic effect of calcitonin in osteoporosis.  Bone. 2002;  30 (5 Suppl) 67S-70S
• 112 Gobelet C, Waldburger M, Meier J L. The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy.  Pain. 1992;  48 (2) 171-175
• 113 Bickerstaff D R, Kanis J A. The use of nasal calcitonin in the treatment of post-traumatic algodystrophy.  Br J Rheumatol. 1991;  30 (4) 291-294
• 114 Adami S, Fossaluzza V, Gatti D, Fracassi E, Braga V. Bisphosphonate therapy of reflex sympathetic dystrophy syndrome.  Ann Rheum Dis. 1997;  56 (3) 201-204
• 115 Varenna M. et al . Intravenous clodronate in the treatment of reflex sympathetic dystrophy syndrome. A randomized, double blind, placebo controlled study.  J Rheumatol. 2000;  27 (6) 1477-1483
• 116 AbuRahma A F, Robinson P A, Powell M, Bastug D, Boland J P. Sympathectomy for reflex sympathetic dystrophy: factors affecting outcome.  Ann Vasc Surg. 1994;  8 (4) 372-379
• 117 Schwartzman R J, Liu J E, Smullens S N, Hyslop T, Tahmoush A J. Long-term outcome following sympathectomy for complex regional pain syndrome type 1 (RSD).  J Neurol Sci. 1997;  150 (2) 149-152
• 118 Furlan A D, Mailis A, Papagapiou M. Are we paying a high price for surgical sympathectomy? A systematic literature review of late complications.  J Pain. 2000;  1 (4) 245-257
• 119 Furlan A D, Lui P W, Mailis A. Chemical sympathectomy for neuropathic pain: does it work? Case report and systematic literature review.  Clin J Pain. 2001;  17 (4) 327-336
• 120 Forouzanfar T, Kemler M A, Weber W E, Kessels A G, Kleef M van. Spinal cord stimulation in complex regional pain syndrome: cervical and lumbar devices are comparably effective.  Br J Anaesth. 2004;  92 (3) 348-353
• 121 Kemler M A, De Vet H C, Barendse G A, Wildenberg F A van den, Kleef M van. The effect of spinal cord stimulation in patients with chronic reflex sympathetic dystrophy: two years' follow-up of the randomized controlled trial.  Ann Neurol. 2004;  55 (1) 13-18
• 122 Hassenbusch S J, Stanton-Hicks M, Schoppa D, Walsh J G, Covington E C. Long-term results of peripheral nerve stimulation for reflex sympathetic dystrophy.  J Neurosurg. 1996;  84 (3) 415-423