Scientific Studies


This page has been designed for those of you with a scientific approach who prefer the research literature about RSD/CRPS.Many new things are happening in the CRPS research field. There are many labs around the world now working on RSD/CRPS: Israel, Turkey, Japan, Switzerland, South Korea,,Sweden, Germany, Canada, Japan, The Netherlandsand in USA.

CRPS SIG (Special Interest Group) consists of CRPS researchers. All of these doctors/researchers have published papers and are dedicated to finding out more about the cause, treatments and cure for CRPS. Their yearly IASP CRPS conference offers new and emerging concepts in CRPS research.Please see our Conferences page for details on this year's confernce.

Please also see our Canadian Research page for information into 2017.

UPDATE 2017: The newest research is posted on our Facebook page: RSDCANADA:PARC.

Since CRPS research is a large area, we advise you to begin with the list below and then expand to the next row of links.

General Reading List Studies 2001-1999 SPREAD of CRPS CRPS Guidelines Dr. H. Hooshmand

Dutch Research

NOTE: CRPS studies are listed by year and important ones are highlighted.

Studies 2002-3 Studies 2004

Studies 2005-7

Studies 2008-12


After 2012, the CRPS research is listed on our Facebook page: RSDCANADA:PARC.



  • Abu, Rahma A, Robinson P et al Sympathectomy for reflex sympathetic dystrophy: Factors affecting outcome.Ann Vasc Surg 1994; 8: 372-379
  • Boas, R. Sympathetic nerve blocks in the evaluation of chronic pain: A plea for caution in their use and interpretation Anesthesiology 1997 86: 4-6
  • Bruehl, S. Husfeldt B, et al Psychological differences between Reflex Sympathetic Dystrophy and non-RSD chronic pain patients Pain 1996 67: 107-114
  • Davis, K, Treede R, Raja S. Topical application of clonidine relieves hyperalgesia in patients with sympathetically maintained pain Pain 1991 47: 309-318
  • Geertzen, JHB et al Reflex Sympathetic Dystrophy:Early Treatment and Psychological Aspects Arch Phys Med Rehabilitation Vol 75 April 1994 442445
  • Hooshmand, H. MD Hashmi, M MDComplex regional pain syndrome (RSD) Diagnosis and Therapy-A review of 824 Patients Pain Digest Springer-Verlag New York Inc. 1999
  • Janig, W., Stanton-Hicks, M. Eds. Reflex Sympathetic Dystrophy: A ReappraisalProgress in Pain Research and Management.Vol. 6 Seatlle IASP Press 1996.
  • Kirkpatrick A, Derasari M, Transdermal clonidine: Treating reflex sympathetic dystrophy Regional Anesthesia 1993 18: 140-141
  • Krames, E. MD Intraspinal opiod therapy for chronic nonmalignant pain: current practice and clinical guidelines J Pain Symptom Management 1996;11: 333-352
  • Linchitz R. MD Raheb J Subcutaneous Infusion of Lidocaine Provides Effective Pain Relief for CRPS Patients Clin J Pain 15; 67-72
  • Merskey, H. Bogduk N. Eds. Classification of chronic pain: pain syndromes and definition of pain Second Edition Seattle IASP Press 1996
  • Raja, S, Turnquest et al Monitoring the adequacy of alpha-adrenergic blockade following systemic phentolamine administration Pain 1996;64: 197204
  • Schwartz, RG MD Electric sympathetic block: current theroetical concepts and clinical results J Back and Musculoskeletal Rehab 1998;10: 31-46
  • Schwartz, RG et al Diagnostic paraspinal musculoskeletal ultrasonography J Back Musc Rehab 1999;12: 25-33
  • Schwartzman, R.J., et al: The movement disorder of reflex sympathetic dystrophy Neurology 1990 40: 57-61
  • Schwartzman, R.J., McLellan T.: Reflex Sympathetic Dystrophy, A review Archives of Neurology 1987 44: 555-61
  • Schwartzman, RJ., The autonomic nervous system and pain Handbook of Neurology Ed. Vinken PJ, Bruyn GW Appelnzeller 1999 In press
  • Stanton-Hicks, M. et al Reflex Sympathetic Dystrophy:changing concepts and taxonomy Pain 1995 63:127-33
  • Stanton-Hicks,M, Baron R, et al Consensus Report: Complex regional pain syndromes:Guidelines for Therapy Clin Journal of Pain 1998: 14: 155-66
  • Van der Laan L. et al A Novel Animal Model to Evaluate Oxygen Derived Free Radical Damage in Soft TissueFree Rad Res. Vol 26 pp 363-72
  • van der Laan L., Goris RJ Reflex Sympathetic Dystrophy: An Exaggerated Inflammatory Response? Hand Clinics Vol 13 No 3 August 1997 p 373-385
  • van der Laan, L et al Complex Regional Pain Syndrome type 1 (RSD) Pathology of skeletal muscle and peripheral nerve Neurology 1998; 51: 2025
  • Veldman, PHJM et al Signs and symptoms of reflex sympathetic dystrophy:prospective study of 829 patients Lancet Vol 342 Oct. 23, 1993 p 1012-5
  • Veldman, PHJM Goris RJA Surgery on extremities with reflex sympathetic dystrophy Unfallchirug 1995; 98:45-8
  • Veldman, PHJM Shoulder complaints in patients with RSD of the upper extremity Arch Phys Med Rehabilitation Vol 76 March 1995 p 239-441
  • Veldman, PHJM Goris RJA Multiple RSD:Which patients are at risk for developing a recurrence of RSD in the same or another limb? Pain 64 1996; 463-66
  • Wilder, R. et al Reflex Sympathetic Dystrophy in Children J of Bone and Joint surgery Vol 74-A No.6 July 1992 p 910-919
  • Wilder, R RSD in Children and Adolescents:Differences from AdultsRSD:A Reappraisal Vol 6 IASP Press Seattle 1996

STUDIES 2001-1999

This section contains journal articles listed alphabetically by author and categorized by year. First are the 2001 studies, then 2000 and 1999. Some citations contain brief descriptions. Those with a Pub Med ID number (e.g. PMID 11114289) may be searched for by number at Pub Med.

Please take time to read the "Most Valuable Study" of 2000 by Dr.R. Schwartzman.


Alvarez-Lario B, Aretxabala-Alcibar I, Alegre-Lopez J, Alonso-Valdivielso JL Acceptance of the different denominations for reflex sympathetic dystrophyAnn Rheum Dis. 2001 Jan;60(1):77-9. PMID: 11114289

Birklein et al Theory of increased neuropeptides release from peripheral nociceptors as a possible pahtological mechanism for RSD. Pain 2001 Apr;91;(3):251-7 PMID 11275381 "Electrically induced neurogenic vasodilation and protein extravasation were evaluated in patients. Neurogenic inflammation is facilitated in CRPS and leads to an increased releasability of neuropeptides."

Geiderman JM.Sympathetic dystrophy. Ann Emerg Med 2001 Apr;37(4):412-4 Ruth and Harry Roman Emergency Department, Department of Emergency Medicine, Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. PMID: 11275838

Hewitt DJ.Web alert Curr Pain Headache Rep 2001 Feb;5(1):3-4 PMID: 11320993

Leong, MS Machey S. Delayed subdural block after a stellate ganglion block Anesth 2001 Feb;94 (2):358-9 PMID:11176103

Takahiro Ushida W. Willis Changes in dorsal horn neuronal responses in experimental wrist contracture model J Ortho Sc. Vol. 6 Issue 1 pp. 46-52 ISSN 0949-2658.
No abstract is available.

Our latest and greatest updated file on 2001 studies is here. See the latest.

If you wish the full text article you may also try: or



MOST VALUABLE STUDY: Documenting the spread of CRPS

Maleki J, LeBel AA, Bennett GJ, Schwartzman RJ Patterns of spread in complex regional pain syndrome, type I (reflex sympathetic dystrophy). Pain 2000 Dec 1;88(3):259-66 Department of Neurology, MCP Hahnemann University, Broad & Vine Street (Mail Stop 423), Philadelphia, PA 19102-1192, USA.

This study is an accurate analysis of the patterns of spread in CRPS. They are identified as "Contiguous spread (CS)' (noted in all 27 cases),. 'Independent spread (IS)' ( in 19 patients (70%)) e.g. CRPS-I/RSD appearing first in a foot, then in a hand). 'Mirror-image spread (MS)' (in 4 patients) There is the possibility that all three kinds of spread may be due to "aberrant CNS regulation of neurogenic inflammation." Source: Academic Press. PMID: 11068113



Birklein et al Increased skin lactate in CRPS Neurology 2000 Oct. 24;55(8)1213-5 PMID 11071503
This study focused on "oxygen metabolism in CRPS and measured skin lactate via dermal microdialysis and blood lactate. Venous lactate was not altered but skin lactate increased in CRPS patients suggesting that enhanced anaerobic glycolysis from tissue hypoxia."

Birklein et al Experimental tissue acidosis leads to increased pain in CRPS Pain 2000 Aug;87(2);227-34 PMID 10924810
The role of local acidosis in generation of pain is examined. Pain was found in the skin but generated in deep somatic tissue of limb.

Dunn D. Manchikanti L. Oberlander TF. Robeson P. Ward V. Huckin RS. Kamani A. Harpur A. McDonald W. Chronic regional pain syndrome, type 1: Part I. AORN J 2000 Sep;72(3):422-32, 435-49; quiz 452-8
This article is an overview of CRPS in two parts. Part I discusses background information such as pain, pathophysiology, diagnosis, clinical stages, and the most common treatment modality, sympathetic nerve blocks. Part II, discusses alternate treatment modalities, such as sympathectomy, physical therapy, stimulators, trigger point injections, acupuncture, tourniquet effects, placebo effects, and amputation.

Geusens P. Santen M. Muir JM. Vernon H. Dunn D. Manchikanti L. Oberlander TF. Robeson P. Ward V. Huckin RS. Kamani A. Harpur A. McDonald W. Algodystrophy. Baillieres Best Pract Res Clin Rheumatol 2000 Sep;14(3):499-513
Various issues in CRPS are examined including the need for a better understanding of the pathophysiology and for prospective clinical studies about the natural course and the effect of treatment.

Goldstein DS et al Sympathetic innervation and function in RSD Ann Neurol 2000 Jul;48(1) 49-59 PMID 10894215
Abstract not available.

Manchikanti L. Oberlander TF. Robeson P. Ward V. Huckin RS. Kamani A. Harpur A. McDonald W. The role of radiofrequency in the management of complex regional pain syndrome. Curr Rev Pain 2000;4(6):437-44
This study examines various treatments and discusses RFTC techniques for CRPS.

Muir JM. Vernon H. Dunn D. Manchikanti L. Oberlander TF. Robeson P. Ward V. Huckin RS. Kamani A. Harpur A. McDonald W. Complex regional pain syndrome and chiropractic. J Manipulative Physiol Ther 2000 Sep;23(7):490-7
This article examines the various theories regarding CRPS and the role of chiropractic treatment.

Muller, LP, Muller LA, Hap J, Kerschbaumer F, Johannes Gutenburg-Universitat Mainz, Klinik und Poliklinik fur Unfallchirurgie, Germany. Frozen Shoulder: a sympathetic dystrophy? Arch Ortho Trauma Surg 2000;120(1-2);84-7
Features of frozen shoulder syndrome and Sudeck's syndrome are similar in many ways; Radioisotope bone scan shows an increased uptake in affected areas in both diseases, and native radiographs show progressive demineralization. Bone mineral density (BMD) pointed to local decalcification processed in early stage of frozen shoulder syndrome. Several studies support the idea that frozen shoulder is a part of CRPS and our observations support this.

Oaklander AL et al Skin biopsies provide objective evidence of injury to nociceptors in patients with CRPS Program and Abstract of 125th Annual Meeting of American Neurol. Association Oct 15-18, 2000 Boston MA Abstract 49
Biopsies showed reduced epidermal neurites 40-100% in density within CRPS areas. Skin biopsies are useful for finding neurologic damage and damage to cutaneous nociceptors.

Oerlemans HM; Oostendorp RA; de Boo T; van der Laan L; Severens JL; Goris RJA; Adjuvant physical therapy versus occupational therapy in patients with RSD/CRPS type 1. Allied Health Services, University Hospital Nijmegen, The Netherlands Archives of Physical Medicine and Rehabilitation 2000 Jan;81(1):49-56
This study is to investigate the effectiveness and cost of physical therapy (PT) or occupational therapy (OT) in patients with RSD At two university hospitals, 135 patients with RSD who have it for less than one year in one upper extremity, were divided into PT, OT and a control group. Results were: improvement in impairment level suniscore (ISS) over one year (Student's test). Clinically relevant was the difference of 5 ISS points between the groups. Severity of disability and handicap was measured and cost effectiveness of the group was analyzed. Results: PT and OT had a significant and more rapid improvement in the ISS as compared with control groups. OT was discovered to have a positive trend. On a handicap level, no difference were found between groups. PT was more cost-effective than OT. In different ways PT and OT both help in the recovery from RSD of upper extremity

Stutts JT. Kasdan ML. Hickey SE. Bruner A. Oberlander TF. Robeson P. Ward V. Huckin RS. Kamani A. Harpur A. McDonald W. Tahmoush AJ. Schwartzman RJ. Hopp JL. Grothusen JR. Harke H. Gretenkort P. Ladleif HU. Rahman S. Harke O. Wesdock KA. Stanton RP. Singsen BH. Reflex sympathetic dystrophy: misdiagnosis in patients with dysfunctional postures of the upper extremity. J Hand Surg [Am] 2000 Nov;25(6):1152-6
The purpose of this case-control study was to assess the frequency of the inappropriate diagnosis of reflex sympathetic dystrophy (RSD) in patients who presented with dysfunctional postures of the upper extremity. Patients presenting with dysfunctional postures of the upper extremity may be misdiagnosed as having RSD and rarely meet the criteria for this diagnosis.

Tahmoush AJ. Schwartzman RJ. Hopp JL. Grothusen JR. Harke H. Gretenkort P. Ladleif HU. Rahman S. Harke O. Wesdock KA. Stanton RP. Singsen BH Quantitative sensory studies in complex regional pain syndrome type 1/RSD Clin J Pain 2000 Dec;16(4):340-4
This study focuses on thermal allodynia in CRPS by examining its role. This study suggests that thermal allodynia in patients with CRPS1/RSD results from decreased cold-evoked and heat-evoked pain thresholds. The thermal pain thresholds are reset (decreased) so that non-noxious thermal stimuli are perceived to be pain (allodynia).

van Hilten, JJ MD et al Intrathecal Baclofen for the Treatment of Dystonia in Patients with Reflex Sympathetic Dystrophy N England J Med 2000;343;625-30
A benchmark in RSD studies; intrathecal baclofen as a treatment for dystonia associated with RSD.
van der Beek WJ van Hilten JJ et al HLA-DQ1 associated with reflex sympathetic dystrophy Neurology 2000 Aug8;55(3) 457-8 PMID 10932297
No abstract available.

van Hilten JJ MD et al Multifocal or Generalized Tonic Dystonia of Complex Regional Pain Syndrome: A Distinct Clinical Entity Associated with HLA-DR13 Ann Neurology 2000;48:113-116
Patients with CRPS-dystonia have a distinct elevation of HLA-DR13 indicating a susceptibility to this phenotype of CRPS.

Verdugo RJ, Ochoa JL, Dept. of Neurology, Faculty of Medicine, Univ. of Chile, Santiago, Chile. Abnormal movements in CRPS: assessment of their nature Muscle Nerve 2000 Feb23(2):198-295
Abnormal movements such as dystonic spasms, coarse postural or action tremor, irregular jerks, and one choreiform case are a part of the syndrome CRPS. Fifty eight patients were subjected to clinical and laboratory evaluations to determine the nature of their neurological problems. No case of CRPS type 2 (Causalgia) but only cases of CRPS type 1 RSD) showed these abnormal movements. There was no evidence of structural nerve, spinal cord or intracranial damage. All type 1 patients showed psuedo-neurological (nonorganic) signs. This study points to abnormal movements found only in CRPS type 1 and not in type 2. It also is a symptom of an underlying pseudo-neurological disorder

Wheeler DS, Vaux KK, Tan DA, Dept. of Pediatrics and Clinical Investigations Naval Medical Center, San Diego CA.Use of Gabapentin in the treatment of childhood RSD Pediatric Neurology 2000 Mar 1;22(3):220-221



Galer, BS, Jensen M. USA.Neglect-like symptoms in complex regional pain syndrome: results of a self-administered survey Dept. of Pain Medicine and Palliative Care, Beth Israel Medical Center, NY, NY. 10002 Journal Pain Symptoms Management 1999 Sept;18(3):213-7

Oerlemans HM, Oostendorp RA, de Boo T, Perez Goris RJA. Signs and symptoms in CRPS type 1:RSD: judgement of the physician versus objective measurement. Allied Health Services University Hospital Nijmegen, The Netherlands. Clin Journal of Pain 1999 Sept;15(3) 224-32
Diagnostic signs and symptoms of CRPS patients of one upper extremity of one year's duration, were recorded The aim was to assess the relationship between subjective assessed patients and those who were objectively measured and to determine their severity. Tests included: (a) pain by using visual analog scale (VAS), McGill Pain Questionnaire (MPG) (b) edema with a hand volumeter (c)skin temperature with infrared thermometer (d) active range of motion (AROM) with goniometers. Bedside evaluation of CRPS type 1 with Veldman's criteria was in agreement with psychometric or lab test of these criteria. (This study is effective in that it works towards ways to make a definitive diagnosis of CRPS.)

Oerlemans HM, Goris RJA, de Boo T, Oostendorp RA. .Do physical impairment and occupational therapy reduce the impairment percentage in RSD?Allied Health Services, University Hospital Njimegen, The Netherlands Am J Phys Med. Rehabilitation 1999 Nov-Dec;78(6): 533-9

Schwartzman RJ, Maleki J Postinjury neuropathic pain syndromes Department of Neurology, MCP/Hahnemann University, Philadelphia, PA, USA.Med Clin North Am 1999 May;83(3):597-626.
Pain is clearly one of the most daunting problems of modern medicine. Posttraumatic neuropathic pain syndromes are a major component of the clinical problem. Structural lesions affecting roots, nerves, the plexi, and central structures can be imaged non-invasively. The molecular biology of the intraneural cascades that cause sensitization of the central pain-projecting neurons of the dorsal horn and subsequent allodynia, hyperalgesia, and hyperpathia is a subject of intense inquiry. The role of the clinician in identifying and eliminating the source of the pain is crucial before the effects of excitotoxicity and central sensitization permanently alter the physiology of the central pain-projecting neurons and make treatment ineffectual. PMID: 10386117, UI: 99313895

Blair SJ Chinthagada M, Hoppenstedt D, Kirojowski R, Fareed J. Role of Neuropeptides in pathogenesis of RSD. Acto Orthop Belg 1998 64: 448-450

NOTE: Each article has a PMID number which can be used to order the full text of the article or search for the abstract or review at Pub Med (National Library of Medicine) on our links page.You may also try: or



Treatment and management for RSD/CRPS has been a longstanding problem because so many of the experts disagree. The articles below are an effort to come to a consensus about how RSD/CRPS is recognized, diagnosed, treated and managed. In the last year several great articles have synthesized the diagnostic procedures and treatments into a more comprehensive view. It is recommended that if you are an RSD/CRPS patient, you give copies of these articles to your doctor. Below are some excellent efforts.

by M Stanton-Hicks MD et al The Clinical Journal of Pain 1998; 14:155-166

A few years ago, leading US and Canadian doctors and researchers including Canadians Harold Merskey MD and Angela Mailis MD met to design a treatment protocol that all doctors could clearly follow. In essence, it states that treating a complicated disease requires a complex three part approach.The first step is a diagnosis which includes careful attention to all signs and symptoms. Then the treatment plan is designed and begun.

Part A is the medical interventions which include drugs, blocks, surgery or neurmodulation e.g.. TENS, PNS, SCS.Part B begun at the same time, is activation including physical therapy achieved by various methods e.g.. desensitization, flexibility, Peripheral E-stim, and ROM. Part C consists of psychological interventions such as counselling, cognitive behavior, relaxation techniques, imagery, hypnosis or coping skills.

The treatment algorithm is designed in these three parts to facilitate movement through each section and its purpose is to combine all parts to return function to the patient.


by Anthony Kirkpatrick MD et al
At the RSDSA Conference October 15-16,1999, the RSDSA's Research Director, Dr. Anthony Kirkpatrick introduced "Clinical Practice Guidelines" which were written by a committee of 12 RSD doctors and researchers from the USA. The Guidelines explain in great detail what RSD/CRPS is and how it is diagnosed. The most important treatment concept is educating the patient so that he/she can participate in the treatment plan which is precisely described for both doctor and patient. Drugs, physical therapy, and minimizing pain are some of the goals. It also covers the various problems and effects which RSD/CRPS can have on a long term basis. Included is a comprehensive list of references and FAQ's on RSD/CRPS entitled "Fact or Fiction". It was recommended that the patient take the Guidelines to his/her doctor to begin the learning process.




A Review of 824 Patients
Hooshmand, H MD and Masood Hashmi MD
Pain Digest 1999; 9: 1-24 Springer-Verlag New York. Inc.

This article is the most comprehensive and precise paper written about all aspects of CRPS. Dr.Hooshang Hooshmand, a leading neurologist and RSD researcher in Florida, reviews 824 patients over 5 years. He maintains that RSD/CRPS is caused by nerve fibers (neurovascular thermoreceptor C fibers) that become over-sensitized to norepinephrine (a neurotransmitter)and send unrelenting pain signals to the brain.
Dr Hooshmand reviews current diagnostic and treatment procedures. The four clinical principles of RSD/CRPS are discussed in detail: pain, motor dysfunction, inflammation and limbic system dysfunction. Again, treatment is complex, consisting of physical therapy, avoiding inactivity and ice, prescribing drugs such as NSAIDS, anti-depressants, and opiod antagonists such as Burpenex and Butorphanol. Various types of blocks, e.g.. paravertebral, regional and brachial plexus block also provide effective pain relief. Avoidance of surgery, especially amputation, ice and cast applications are stressed.

NOTE: Please visit one of the most extensive, valuable, medical CRPS sites available on the Net. Dr Hooshmand's Puzzles are of particular interest to patients and professionals alike . Please see our links page or go to:

UDPATE: May 2001. Dr Hooshmand's newest article has just been published in Thermology Intermational.

UPDATE: Dr Hooshmand has retired. We commend him on his excellent work treating CRPS patients and conducting research. Great work, Dr H!!!!!

If you wish to obtain a copy of these publications, please contact the publishers.





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