STUDIES 2002-3


There is an ever increasing body of CRPS research which covers many aspects of this disease. The following is a list of CRPS studies in 2002-3.


A-M N-Z IASP 8/02 2003



Charles Berde MD PhD

Robert Schwartzman MD

Studies A-M

Studies N-Z

International Dutch RSD Conference: Nov. 14-15, 2003.


Charles Berde, M.D., Ph.D., Harvard Medical School, Director, Pain Treatment Service, Boston Children's Hospital, Boston, Massachusetts

Complex regional pain syndrome, type 1 (CRPS1) or reflex sympathetic dystrophy (RSD) is being diagnosed more frequently in children and adolescents. Over the last 12 years, our pain center has examined the demographics, associated medical and lifestyle factors, and responses to treatment in over 450 patients. Some demographic features in children appear different from those described for adults:

(1) Children and adolescents have lower extremity involvement 6 times more often than upper extremity involvement.

(2) Girls are affected roughly 5 times as often as boys.

(3) RSD/CRPS1 is rare below age 8; the incidence increases markedly just before puberty.

(4) Female dancers, gymnasts and competitive athletes comprise a high percentage of the patients.

A high percentage of patients present either confined to crutches or in a wheelchair. School absenteeism is more common in these patients than in a matched population of rheumatology patients. Coexisting psychiatric diagnoses commonly include depression, anxiety disorders, post-traumatic stress disorders, distorted body image and eating disorders, and stressful family dynamics.

Treatments advocated for RSD have varied largely according to subspecialty and training of health providers. A program for prospective evaluation of these patients was established recently with funding from NICHD. Preliminary studies by Dr. Sethna and others on quantitative sensory and autonomic evaluation will be summarized. Treatments under prospective controlled evaluation include physical therapy, cognitive-behavioral interventions, tricyclics and anticonvulsants, and continuous infusion sympathetic blocks.

(summary of Dr. Berde’s presentation at RSDSA's Tampa conference)

Treatment varies according to the individual child. It is essential to maintain a close rapport with the patient and family so that they can understand and cope with the treatment.
Active PT and CBT (cogntive behaviour therapy) are at the top of the list for treatment and a large percentage of kids improve with these two methods. It is a stepwise return to weight bearing and understanding the role of pain. Desensitization and aqua therapy are also used. CBT includes relaxation training, biofeedback and other coping pain skills. Many children recount that CBT helps with daily stress and solving problems. If the pain and limb problem becomes chronic, then treatment for depression or anxiety is considered. Tricyclic antidepressants help with sleep and sometimes anticonvulsants (Neurontin) are used. Finding the right dose of the right drug and assessing side effects are all very important.Those who do not improve with PT and CBT, can receive sympathetic blockade.

Various methods can be used from lumbar paravertebral, lumbar epidural or IV regional with single shot or continuous methods. It depends on the individual case. Invasive procedures are saved for those who have tried all other therapies and did not respond well. These treatments include spinal cord or peripheral stimulation, implantable pumps and sympathectomy. No form of neurodestructive sympathectomy is done due to possible long term complications.

Note: This review article appears in the Winter Issue of the PARC PEARL.


Berde, C.B., & Sethna, N.F. (in press).

Sethna, N.F. (1999). Pharmacotherapy in long-term pain: Current experience and future direction. In P. McGrath, & G.A. Finley (Eds.), Chronic and recurrent pain in children and adolescents. Progress in pain research and management (pp. 243-266). Seattle: IASP Press.

Sherry DD et al Short and long term outcomes of children with CRPS 1 treated with exercise therapy. Clinical Journal of Pain 1999; 15:218-33

Stanton, R.P., Malcolm, J.R., Wesdock, K.A., & Singsen, B.H(1993). Reflex sympathetic dystrophy in children: An orthopedic perspective. Orthopedics, 16, 773-779.

Wilder, R.T., Berde, C.B., Wolohan, M., Vieyra, M.A., Masek, B.J., & Micheli, L.J. (1992). Reflex sympathetic dystrophy in children. Clinical characteristics and follow-up of seventy patients. Journal of Bone & Joint Surgery American Volume, 74, 910-919.


Dr Robert Jay Schwartzman, presenter at the Tampa conference, is a well known expert in the treatment of CRPS in children and adults.He has been treating and researching CRPS for many years and continues to break new ground. He was the first to document the spread of CRPS (see Studies file) and discover the movement disorder component of CRPS. What follows are some of his most recent studies.



CRPS-1 is a very hard to treat syndrome characterized by neuropathic pain. CRPS can spread and become resistant to therapy. More treatments are urgently needed. NMDA receptors are thought play an active role in central pain and NMDA agonists as therapy for CRPS (and neuropathic pain) are being studied.

Ten patients with intractable CRPS-1 were given anesthesia which consisted of ketamine and midazolam for 5 days. Some patients were intubated and some had spontaneous breathing. On day 6 they were slowly tapered from infusions.


All TEN responded by having no pain, no hyperalgesia, no allodynia and an absence of CRPS-1 signs.
Five out of ten had full pain relief for 2 months up to 3.5 years. In 8/10 patients, after 6-8 weeks the original nociceptive pain returned. In 7/8 the pain was at the original injury site. Hyperalgesia and allodynia recurred in 4/10 who then received another ketamine treatment. Success happened in 2/3. Patients were all able to use less pain medication.

The authors are quick to say that this treatment shows potential and could be an effective treatment option for severe CRPS-1. They do raise the following issues: which patients would benefit most, what selection criteria would be used to select patients, when to treat the CRPS, and maintenance schedules for re-treatment.

This is the first attempt at using ketamine anesthesia for intractable CRPS-1 and it does not come without its risks. Patients need to be asleep and monitored carefully during the five day treatment. Perhaps in future trials, a less risky form of treatment can be found.

Source: Schwartzman, RJ et al "Ketamine-Midazolam Anesthesia for Intractable CRPS-1" 2002 presented to IASP 2002 Conference



Skin temperature and color changes are an integral part of CRPS. The skin can turn blue, reddish, mottled, or purple. Temperatures vary from hot to warm or cold. Monitoring skin blood flow changes help clinicians decide on the effectiveness of CRPS treatments e.g. when using sympathetic blocks. One such new promising treatment is ketamine/midazolam anesthesia for chronic CRPS-1. This study is the first of its kind to investigate this treatment.

Data on skin blood flow (SBF) at rest and during vasomotor ic challenge (with heating probe) was collected. Patient's status and responses before, during and after ketamine anesthesia were observed. Could this method be used to asses the ability of the blood vessels to regulate themselves or determine vasomotor impairment in CRPS? Could this be used as a tool to assess treatment success ?

Eight patients with intractable CRPS-1 were analyzed for blood flow with laser doppler flowmetry (PF 4001) and a heating probe was used to raise skin temperature. Patients were measured at rest and during the vasomotor challenge.

Under ketamine anesthesia, a significant increase in SBF was observed in the first 72 hours. Interestingly, the areas of the most pain showed the strongest increase, up to 10 fold. Then SBF normalized and vasomotor reagibility occurred e.g. decreased, edema, hyperemia and temperature changes. When the limb was locally heated, the highest increase of SBF was found on day 2 and 3 of therapy.

The authors are the first to admit that more studies must be done before LDF can be recommended as a diagnostic tool or for therapy. Suggestions include monitoring SBF changes in CRPS, possibly predicting therapeutic success, to quantify vasomotor reactive capacity (rest/vasomotor challenge), to help assess sympathetic activity and to contribute to a piece of the diagnostic puzzle of CRPS. Using LDF as a diagnostic tool would be another first since there is none available at this time.

Source: Schwartzman, RJ et al "Skin Blood Flow Changes During Ketamine/Midazolam Anesthesia for Intractable CRPS-1 2002

Note: Low dose ketamine treatments are now being developed in Canada. Contact us for the name of Canadian doctors offering ketamine treatments. These review articles can be found in the PARC PEARL March issue.


***Argoff CE. A focused review on the use of botulinum toxins for neuropathic pain. Clin J Pain. 2002 Nov-Dec;18(6 Suppl):S177-81.
Cohn Pain Management Center, North Shore University Hospital, New York University School of Medicine, Bethpage, New York 11714, USA.

Understanding the pathophysiology of a pain syndrome is helpful in selecting appropriate treatment strategies. Nociceptive pain is related to damage to tissues due to thermal, chemical, mechanical, or other types of irritants. Neuropathic pain results from injury to the peripheral or central nervous system. Common examples of neuropathic pain include postherpetic neuralgia, diabetic neuropathy, complex regional pain syndrome, and pain associated with spinal cord injuries. Nociceptive pain may have similar clinical characteristics to neuropathic pain. It is also possible for acute nociceptive pain to become neuropathic in nature, as with myofascial pain syndrome. A clear benefit of botulinum toxin therapy for treatment of neuropathic pain disorders is that it often relieves pain symptoms. Although the precise mechanism of pain relief is not completely understood, the injection of botulinum toxin may reduce various substances that sensitize nociceptors. As a result, botulinum toxin types A and B are now being actively studied in nociceptive and neuropathic pain disorders to better define their roles as analgesics.

PMID: 12569966


Basford JR, Sandroni P, Low PA, Hines SM, Gehrking JA, Gehrking TL.Effects of linearly polarized 0.6-1.6 &mgr;M irradiation on stellate ganglion function in normal subjects and people with complex regional pain (CRPS I). Lasers Surg Med. 2003 Jun;32(5):417-423.
Department of Physical Medicine and Rehabilitation, Autonomic Disorder Center, Mayo Clinic and Foundation, 200 Southwest Second Street, Rochester, Minnesota 55905.

BACKGROUND AND OBJECTIVES: Stellate ganglion blocks are an effective but invasive treatment of upper extremity pain. Linearly polarized red and near-infrared (IR) light is promoted as a safe alternative to this procedure, but its effects are poorly established. This study was designed to assess the physiological effects of this latter approach and to quantitate its benefits in people with upper extremity pain due to Complex Regional Pain Syndrome I (CRPS I, RSD). STUDY DESIGN/MATERIALS AND METHODS: This was a two-part study. In the first phase, six adults (ages 18-60) with normal neurological examinations underwent transcutaneous irradiation of their right stellate ganglion with linearly polarized 0.6-1.6 &mgr;m light (0.92 W, 88.3 J). Phase two consisted of a double-blinded evaluation of active and placebo radiation in 12 subjects (ages 18-72) of which 6 had upper extremity CRPS I and 6 served as "normal" controls. Skin temperature, heart rate (HR), sudomotor function, and vasomotor tone were monitored before, during, and for 30 minutes following irradiation. Analgesic and sensory effects were assessed over the same period as well as 1 and 2 weeks later. RESULTS: Three of six subjects with CRPS I and no control subjects experienced a sensation of warmth following active irradiation (P = 0.025). Two of the CRPS I subjects reported a >50% pain reduction. However, four noted minimal or no change and improvement did not reach statistical significance for the group as a whole. No statistically significant changes in autonomic function were noted. There were no adverse consequences. CONCLUSIONS: Irradiation is well tolerated. There is a suggestion in this small study that treatment is beneficial and that its benefits are not dependent on changes in sympathetic tone. Further evaluation is warranted. Lasers Surg. Med. 32:417-423, 2003. Copyright 2003 Wiley-Liss, Inc.

PMID: 12766967

Bennett GJ. Are the complex regional pain syndromes due to neurogenic inflammation?
Neurology. 2001 Dec 26;57(12):2161-2.
Comment on:
Neurology. 2001 Dec 26;57(12):2179-84.
PMID: 11756591

***Cordivari, MD 1 2, V. Peter Misra, MD, FRCP 1, Santiago Catania, MRCP 1, Andrew J. Lees, MD, FRCP 2 *
Treatment of dystonic clenched fist with botulinum toxin.
Mov Disord. 2001 Sep;16(5):907-13.
Department of Clinical Neurophysiology, The National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom
2Reta Lila Weston Institute of Neurological Studies, University College of London, United Kingdom
email: Andrew J. Lees (

* Correspondence to Andrew J. Lees, Reta Lila Weston Institute of Neurological Studies, Windeyer Building, 46 Cleveland Street, University College of London W1T 4JF, UK
A videotape accompanies this article.

Fourteen patients with dystonic clenched fist (three with Corticobasal Ganglionic Degeneration, seven with Parkinson's disease, and four with Dystonic-Complex Regional Pain Syndrome) were treated with botulinum toxin A (BTXA, Dysport®). The muscles involved were identified by the hand posture and EMG activity recorded at rest and during active and passive flexion/extension movements of the finger and wrist. EMG was useful in distinguishing between muscle contraction and underlying contractures and to determine the dosage of BTX. All patients had some degree of flexion at the proximal metacarpophalangeal joints and required injections into the lumbricals. The response in patients depended on the severity of the deformity and the degree of contracture. All patients had significant benefit to pain, with accompanying muscle relaxation, and palmar infection, when present, was eradicated. Four patients with Parkinson's disease and one patient with Dystonia-Complex Regional Pain Syndrome obtained functional benefit. © 2001 Movement Disorder Society.
Received: 18 December 2000; Revised: 4 April 2001; Accepted: 19 April 2001

***Kobana,M. S. Leisa, S. Schultze-Mosgaub and F. Birklein
Tissue hypoxia in complex regional pain syndrome
c/a Neurologische Klinik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, D-91054, Erlangen, Germany
b Klinik für Mund-, Kiefer- und Gesichtschirurgie Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 17, D-91054, Erlangen, Germany c Neurologische Klinik, Johannes Gutenberg-Universität Mainz, Langenbeckstraße 1, D-51101, Mainz, Germany
Received 26 February 2002; accepted 6 December 2002. ; Available online 14 May 2003.

Untreated complex regional pain syndrome (CRPS) may progress from acute stages with increased hair and nail growth in the affected limb to chronic stages with atrophy of the skin, muscles and bones. The aim of this study was to investigate whether tissue hypoxia could be one mechanism responsible for this late CRPS symptoms.

Nineteen patients with CRPS and two control groups (healthy control subjects, surgery patients with edema) participated in this study. Skin capillary hemoglobin oxygenation (HbO2 ) was measured non-invasively employing micro-lightguide spectrophotometry (EMPHO). The EMPHO probe was mounted force-controlled onto the skin of the affected and unaffected hand. HbO2 was measured at rest and during postischemic reactive hyperemia.

HbO2 did not differ between the right (58.20%±1.12) and left (57.79%±1.31, ns) hand in control subjects. However, in patients, HbO2 of the affected side (36.63%±2.16) was significantly decreased as compared to the clinically unaffected side (46.35%±2.97, P<0.01). As compared to controls, HbO2 in CRPS was reduced on both sides (P <0.001). Postischemic hyperoxygenation was impaired on the affected side in CRPS (60.81%±2.90) – as compared to the unaffected side (67.73%±1.50, P<0.04) and to controls (68.63%±0.87, P<0.005). The unaffected limb in CRPS did not differ from controls. Despite skin edema, pre- (49.06%±2.02) and postsurgery HbO2 (53.15%±4.44, ns) were not different in the second control group.

Our results indicate skin hypoxia in CRPS. Impairment of nutritive blood flow in the affected limb may be one factor contributing to atrophy and ulceration in chronic CRPS. The investigation of patients after surgery revealed that edema could not be the only reason for hypoxia.

[Corresponding Author Contact Information] Corresponding author. Tel.: +49-6131-173270; fax: +49-6131-175625

Kuczkowski, KM. Bretylium in the treatment of complex regional pain syndrome: uncommon side-effect of a common drug. Anaesthesia 2003 Feb;58(2):201-2 Letter.
PMID: 12562438




McCabe CS, Haigh RC, Ring EF, Halligan PW, Wall PD, Blake DR. A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1).
Rheumatology (Oxford) 2003 Jan;42(1):97-101
The Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK.

BACKGROUND: We assessed mirror visual feedback (MVF) to test the hypothesis that incongruence between motor output and sensory input produces complex regional pain syndrome (CRPS) (type 1) pain. METHODS: Eight subjects (disease duration > or =3 weeks to < or =3 yr) were studied over 6 weeks with assessments including two controls (no device and viewing a non-reflective surface) and the intervention (MVF). Pain severity and vasomotor changes were recorded. RESULTS: The control stages had no analgesic effect. MVF in early CRPS (< or =8 weeks) had an immediate analgesic effect and in intermediate disease (< or =1 yr) led to a reduction in stiffness. At 6 weeks, normalization of function and thermal differences had occurred (early and intermediate disease). No change was found in chronic CRPS. CONCLUSIONS: In early CRPS (type 1), visual input from a moving, unaffected limb re-establishes the pain-free relationship between sensory feedback and motor execution. Trophic changes and a less plastic neural pathway preclude this in chronic disease.

PMID: 12509620


Parisod E, Murray RF, Cousins MJ.
Conversion disorder after implant of a spinal cord stimulator in a patient with a complex regional pain syndrome. Anesth Analg 2003 Jan;96(1):201-6, University of Sydney, Pain Management & Research Centre, Royal North Shore Hospital, St. Leonards, Australia.

IMPLICATIONS: This case history describes the treatment of a patient suffering with persistent pain. He was treated surgically with implantation of a spinal cord stimulator. After surgery, a partial paralysis that could not be explained medically and that was probably related to emotional factors occurred, and cognitive behavioral treatment was begun. This paper discusses the importance of considering social and psychological factors when medical treatment options are considered.

PMID: 12505953

***Sandroni,P., Lisa M. Benrud-Larson, Robyn L. McClelland and Phillip A. Low Complex regional pain syndrome type I: incidence and prevalence in Olmsted county, a population-based study
Mayo Clinic, 200 First Stret SW, Rochester, MN 55905, USA
Received 5 September 2002; accepted 9 December 2002. ; Available online 8 May 2003.


The objective of this study is to undertake a population based study on the incidence, prevalence, natural history, and response to treatment of complex regional pain syndrome (CRPS). All Mayo Clinic and Olmsted Medical Group medical records with codes for reflex sympathetic dystrophy (RSD), CRPS, and compatible diagnoses in the period 1989–1999 were reviewed as part of the Rochester Epidemiology Project. We used IASP criteria for CRPS. The study population was in the Olmsted County, Minnesota (1990 population, 106,470). The main outcome measures were CRPS I incidence, prevalence, and outcome. Seventy-four cases of CRPS I were identified, resulting in an incidence rate of 5.46 per 100,000 person years at risk, and a period prevalence of 20.57 per 100,000. Female:male ratio was 4:1, with a median age of 46 years at onset. Upper limb was affected twice as commonly as lower limb. All cases reported an antecedent event and fracture was the most common trigger (46%). Excellent concordance was found between symptoms and signs and vasomotor symptoms were the most commonly present. Three phase bone scan and autonomic testing diagnosed the condition in >80% of cases. Seventy-four percent of patients underwent resolution, often spontaneously. CRPS I is of low prevalence, more commonly affects women than men, the upper more than the lower extremity, and three out of four cases undergo resolution. These results suggest that invasive treatment of CRPS may not be warranted in the majority of cases.

[Corresponding Author Contact Information] Corresponding author. Tel.: +1-507-284-2090; fax: +1-507-266-6754


Schasfoort FC, Bussmann JB, Zandbergen AM, Stam HJ.
Impact of upper limb complex regional pain syndrome type 1 on everyday life measured with a novel upper limb-activity monitor.
Pain 2003 Jan;101(1-2):79-88

Department of Rehabilitation Medicine, Erasmus MC, University Medical Center Rotterdam, PO Box 1738, 300 DR Rotterdam, Rotterdam, The Netherlands.

Complex regional pain syndrome type 1 (CRPS1) often leads to serious activity limitations in everyday life. To date, however, limitations in patients with CRPS1 of an upper limb have not been objectively measured .Therefore, the aim of this study was to determine the long-term impact of upper limb CRPS1 on general mobility and upper limb usage during everyday life, as measured with a novel upper limb-activity monitor (ULAM). In ten female chronic CRPS1 patients and ten healthy control subjects, 24-h activity patterns were measured with the ULAM. This ULAM consists of body-fixed acceleration sensors, connected to a recorder worn around the waist. The ULAM automatically detects upper limb activity during mobility-related activities. Several outcome measures related to general mobility and upper limb usage were compared between patients and controls. The results showed that CRPSI in the dominant upper limb had modest impact on general mobility; i.e. on the percentages spent in body positions and body motions and on mean intensity of body activity. For upper limb usage outcome measures during sitting, there was a marked difference between CRPS1 patients and controls. Especially patients with dominant side involvement clearly showed less activity of their involved limb during sitting, indicated by significant differences for the mean intensity (P=0.014), percentage (P=0.004), and proportion (P=0.032) of upper limb activity. It is concluded that these ten chronic CRPS1 patients still had limitations in upper limb usage during everyday life, 3.7 years (average) after the causative event.

PMID: 12507702

Schouten AC, Van De Beek WJ, Van Hilten JJ, Van Der Helm FC.
Proprioceptive reflexes in patients with reflex sympathetic dystrophy.
Delft University of Technology, Department of Mechanical Engineering, Man Machine Systems and Control, Mekelweg 2, 2628 CD Delft, Leiden, The Netherlands.

Reflex sympathetic dystrophy (RSD) is a syndrome that frequently follows an injury and is characterized by sensory, autonomic and motor features of the affected extremities. One of the more common motor features of RSD is tonic dystonia, which is caused by impairment of inhibitory interneuronal spinal circuits. In this study the circuits that modulate the gain of proprioceptive reflexes of the shoulder musculature are quantitatively assessed in 19 RSD patients, 9 of whom presented with dystonia. The proprioceptive reflexes are quantified by applying two types of force disturbances: (1) disturbances with a fixed low frequency and a variable bandwidth and (2) disturbances with a small bandwidth around a prescribed centre frequency. Compared to controls, patients have lower reflex gains for velocity feedback in response to the disturbances around a prescribed centre frequency. Additionally, patients with dystonia lack the ability to generate negative reflex gains for position feedback, for these same disturbances. Proprioceptive reflexes to the disturbances with a fixed low frequency and variable bandwidth present no difference between patients and controls. Although dystonia in the RSD patients was limited to the distal musculature, the results suggest involvement of interneuronal circuits that mediate post synaptic inhibition of the motoneurons of the proximal musculature.

PMID: 12743675

Singh B, Moodley J, Shaik AS, Robbs JV.
Sympathectomy for complex regional pain syndrome.
J Vasc Surg 2003 Mar;37(3):508-11
Department of Surgery, Nelson R. Mandela School of Medicine, Faculty of Health Sciences, University of Natal, 4013 Congella, South Africa.

BACKGROUND: With the easier and earlier recognition of complex regional pain syndrome (CRPS), a reappraisal of its therapy, particularly the role and timing of sympathectomy, is warranted. PATIENTS AND METHODS: Over a 9-year period, 42 patients with CRPS type II of the upper extremity were referred for sympathectomy. Patients were categorized according to the duration of the symptoms (group I, <3 months; group II, >3 months). All patients underwent initial medical treatment; stellate ganglion blocks were performed when symptoms persisted beyond 6 weeks. Patients were referred for thoracoscopic sympathectomy on persistence of the pain syndrome. A visual linear analogue scale was used to evaluate outcome of sympathectomy. RESULTS: Thoracoscopic dorsal sympathectomy was successfully undertaken in 32 patients. In the remaining 10 patients, thoracoscopy was not technically feasible and open sympathectomy was performed. There was an overall improvement in all 42 patients undergoing sympathectomy (P <.001, Wilcoxon signed rank test). The outcome in group I was significantly better than in group II (P <.003, Mann-Whitney U test). The diagnosis of sympathetically mediated pain with stellate blockade did not correlate with clinical outcome. Patients undergoing thoracoscopic sympathectomy had a better outcome than those undergoing open sympathectomy. There were no complications, and the hospital stay was shorter in the thoracoscopic group. CONCLUSION: Early recognition of CRPS and prompt recourse to surgical sympathectomy is a useful option in the management of CRPS.

PMID: 12618683


Son UC, Kim MC, Moon DE, Kang JK.
Motor cortex stimulation in a patient with intractable complex regional pain syndrome type II with hemibody involvement. Case report.
J Neurosurg 2003 Jan;98(1):175-9
Department of Neurosurgery, Kangnam St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

The authors describe the effectiveness of motor cortex stimulation (MCS) in a patient with complex regional pain syndrome (CRPS) Type II, formerly known as causalgia, with hemibody allodynia. During MCS, a subjective sensation of warm paresthesia developed in the painful hand and forearm and spread toward the trunk. Pain and allodynia in the areas associated with this sensation were alleviated significantly. The analgesic effect of stimulation proved to be long lasting and was still present at the 12-month follow up. The authors speculate that MCS might exert its effect through the modulation of thalamic activity in this particular case of CRPS with hemisensory deficit. A central mechanism associated with functional disturbance in noxious-event processing in the thalamus might have an important role in the pathogenesis of the condition.

PMID: 12546368


van de Beek WJ, Schwartzman RJ, van Nes SI, Delhaas EM, van Hilten JJ. Diagnostic criteria used in studies of reflex sympathetic dystrophy.
Neurology. 2002 Feb 26;58(4):522-6.
Department of Neurology, Leiden University Medical Center, the Netherlands.

OBJECTIVE: Assessment of the diagnostic criteria of reflex sympathetic dystrophy (RSD) and evaluation of the impact of the introduction of the diagnostic criteria of complex regional pain syndrome (CRPS) on the international application of diagnostic criteria of RSD. METHODS: Randomized controlled trials and clinical investigations, published between January 1980 and June 2000, were evaluated with regard to the applied diagnostic criteria of RSD. RESULTS: One hundred seven studies were identified. Thirty-four of these studies were excluded because of inadequate reporting of diagnostic criteria. The 73 included studies were not homogeneous with regard to the diagnostic criteria because they applied many different aspects of sensory and autonomic features. Only 12% of the studies considered the presence of motor features, mostly vaguely described, as mandatory for the diagnosis RSD. Although 10 of the 23 studies published since the introduction of CRPS have applied this term, only 3 used the exact criteria without additions or other modifications. CONCLUSION: Diagnostic criteria sets of RSD focus on many different aspects of sensory and autonomic features that generally are described vaguely. This has not changed since the introduction of the CPRS criteria. These findings question whether the current criteria adequately define RSD.

PMID: 11865127

***van de Beek WJ, Vein A, Hilgevoord AA, van Dijk JG, van Hilten BJ.
Neurophysiologic aspects of patients with generalized or multifocal tonic dystonia of reflex sympathetic dystrophy.
J Clin Neurophysiol. 2002 Jan;19(1):77-83.
Department of Neurology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.

Reflex sympathetic dystrophy (RSD) is a syndrome dominated by sensory, autonomic, and motor features of the extremities. In this study, 10 severely affected RSD patients who progressed to multifocal or generalized tonic dystonia underwent H-reflex evaluation, needle electromyography (EMG), polysomnography, somatosensory evoked potentials, and transcranial magnetic stimulation. H-reflex evaluation revealed an impaired vibratory inhibition of the H-reflex and a higher facilitation peak in the recovery curve between 200 to 350 msec. Needle EMG revealed an impaired reciprocal inhibition, and many patients were unable to alter the amount of muscle activity voluntarily. Evaluations of the stretch reflex showed a markedly decreased threshold and abnormal responses to tonic and phasic changes. Polysomnography performed in five patients revealed no abnormal EMG activity during nonrapid eye movement and rapid eye movement sleep, but EEG arousal phenomena provoked abnormally high and brief bursts of surface EMG activity in all registered muscle groups. Somatosensory evoked potentials and transcranial magnetic stimulation were normal. Taken together, the findings in these patients with tonic dystonia of RSD are in accordance with an impairment of inhibitory interneuronal circuits at the level of the brainstem or spinal cord.

PMID: 11896357


***van de Beeka, Willem-Johan T., Bart O. Roepb, Arno R. van der Slikb, Marius J. Giphartb and Bob J. van Hilten,
Susceptibility loci for complex regional pain syndrome
a) Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands b) Department Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
Received 11 April 2002; accepted 22 October 2002. ; Available online 27 March 2003.

An association between HLA-DR13 and patients with complex regional pain syndrome (CRPS) who progressed towards multifocal or generalized tonic dystonia was recently reported. We now report on a new locus, centromeric in HLA-class I, which was significantly associated with a spontaneous development of CRPS, suggesting an interaction between trauma severity and genetic factors conferring CRPS susceptibility. Additionally, an association with the D6S1014 locus was found, supporting the previous finding of an association with HLA-DR13.
[Corresponding Author Contact Information] Corresponding author. Tel.: +31-71-526-2895; fax: +31-71-524-8253


NOVEMBER 14-15 , 2003.


R. Baron, Klink fur Neurologie, Christian-Alrechts-Universitat, Kiel, Germany,

The striking response of neuropathic pain syndromes such as CRPS (CRPS, causalgia) and RSD to
sympatholytic procedures together with signs of autonomic nervous system abnormalities suggest that the
sympathetic efferent system can generate or enhance pain (SMP) and may be involved in the dysregulation of skin blood flow and sweating. Evidence from animal experiments: There is convincing evidence from animal studies that after complete and partial nerve injury both damage and undamaged nociceptive C-fibers acquire a chemical sensitivity to noradrenergic agents and can be activated by sympathetic - trunk stimulation. This sympatho-afferent transmission is mediated by alpha 2 adrenoreceptors Accordingly, mRNA for alpha 2-Aadrenoreceptors is up-regulated in DRG neurons after nerve transection.

Pathophysiology of SMP in patients: The adrenergic influence on afferents in humans was analyzed in
patients with CRPS type 2. In a subgroup of patients with SMP, intracutaneous application of
alpha-adrenergic agents enhances pain and hyperalgesia. Accordingly, autoradiographic studies indicate
that the number of alpha-1-adrenorecptrs in hyperalgesic skin of patients with SMP is significantly greater
than in the skin of normal subjects. Further more, it could be demonstrated in CRPS1 that spontaneous
pain and mechanical hyperalgesia was augmented when sympathetic cutaneous vasoconstrictor neurons
were activated physiologically by thermoregulatory cold stress. There was a high correlation between pain relief during sympathetic blocks and augmentation of pain during sympathetic chain activation. The latter results show that also sympathetic activity modulated in physiological ranges and endogenous
noradrenaline release is able to enhance pain in CRPS.

Autonomic abnormalities in patients: Controlled thermoregulatory reflexes (Whole body warming, cooling) were used to experimental regulation patterns were identified related to the duration of the disorder: in the warm regulation type (acute stage) the affected limb was warmer and skim perfusion values were higher than contralaterally during the entire spectrum of sympathetic activity, Even massive body cooling failed to activate sympathetic vasoconstrictor neurons. In the intermediate type temperature and perfusion were either warmer or colder depending on the degree of sympathetic activity. In the cold type (Chronic stages) temperature and perfusion were lower on the affected side during the entire thermoregulatory cycle.

In conclusion, a central unilateral inhibition of cutaneous sympathetic vasoconstrictor neurons leads to a
warmer affected limb in the acute stage. Secondary changes in the neurovascular transmission induce
vasoconstriction and cold skin in chronic CPRS. The maximal skin temperature difference between the
affected and unaffected extremity that occurs during the theromregulatory cycle can be sued as a
diagnostic tool. With high sensitivity and specificity it distinguishes CRPS from other extremity pain

RJA Goris, MD University Hospital Nijmegen, Dept. of Surgery, Nijmegen.

The majority of scientific publications on RSD/CRPS I address late problems relating to pain, tissue
dystrophy, and atrophy and neurological changes. However, in the early phase, signs and symptoms of
inflammation are prominent. Acute inflammation in RSD could be documented by studying the
extravasation of immunoglobulin in the affected extremity. Also, morphologically, signs of tissue damage
could be demonstrated in skeletal muscle, related to tissue damage caused by toxic oxygen radicals. Such
alterations could be reproduced in an experimental model of oxygen radical-induced skeletal muscle
damage in the rat. The therapeutic effect of oxygen radical scavengers and corticosteroids in acute RSD
also indicates the role of these compounds in generating pathological changes.
The problem of performing “normal” skeletal muscle work with an RSD-affected extremity was objectified by NMR-spectroscopy studies indicating that at tissue level, the supply and or utilization of oxygen in impaired. which also is a characteristic encountered in severe inflammation. As a consequence oxygen extraction in the affected limb is impaired, as shown by elevated venous oxygen saturation levels. In a recent study, the inflammatory response to a Colles fracture was prospectively studied in 115 patients. A wide variety was found in the severity of the inflammatory reaction, After one year. follow-up, the incidence of RSD in these will be documented and the early response related to late RSD.
Many problems still have to be elucidated in RSD such as why patient develops RSD and most others do
not. Studying the genetic characteristics in respect to generating an exaggerated inflammatory response,
may be one of the pathways to explore further.

1. Veldman PHJM et al Signs and symptoms of RSD Lancet 1993
2. Goris RJA RSD World Jour Surg 1998
3. van der Laan L Goris RJA Sudeck Syndrome Unfallchir 1997
4. van der Laan, Goris RJA RSD Hand Cline 1997
5. Oyen WJG et al RSD of the hand Pain 1993
6. van der Laan et al CRPS 1 RSD Neurology 1998
7. van der Laan L et al A novel animal model Free Rad Res. 1997
8. Goris RJA et al Are toxic oxygen radical... Free Rad RES Comms 1987
9. Heereschap A et al; Metabolic changes in RSD Muscle Nerve 1993
10. Goris RJA Conditions associated with impaired O2 extraction Springer Verlag 1991
11. Vaneker M et al Genetic factors associated with CRPS Disability Med 2002

F Birklein, Dept. of Neurology, University Clinic, Mainz, Germany.

Many clinical symptoms of acute CRPS resemble inflammation--pain,edema, increased skin temperature
and blood flow. However, inflammation in the classical sense has not been unequivocally proven. Rather
the coincidence, of inflammatory signs with trophic changes (hair, growth, high-turnover osteoporosis) and mechanical hyperalgesia without hyperalgesia to heat strongly suggests “neurogenic” inflammation.
Trauma related activation of primary afferents cause neuropeptide release in the affected body region
(mainly substance P (SP) and calcitonin-gene related peptide (CRGP) and chronic release of neuropeptides might be responsible for the above mentioned peripheral CRSP symptoms. In addition, central neuropeptide release facilitates nociceptitve sensitization and may cause motor disturbances.

After experimental nerve lesions experiments in rats have shown that neuropeptides, in particular SP,
contribute to pain behaviour and many clinical symptoms resembling CRPS. In analogy to migraine studies, we therefore measure CGRP (RIA) in serum samples from patients with acute CRPS. CGRP was significantly increase, in particular when clinical inflammatory signs were pronounced and if there was
evidence for trauma related nerve lesion. In order to verify that increased CGRP indeed comes from
primary nociceptive afferents, neurogenic inflammation was elicited directly in the skin by transcutaneous
electrical stimulation via intraderrmal microdialysis capillaries, We first investigated the flare by
Laser-Doppler scanning on the affected and on the unaffected side in our CRPS patients. Neurogenic
flare was significantly more intense in patients, surprisingly on both side, the affected and the
clinically unaffected one.

Another characteristic of neurogenic inflammation in rodents is SP mediated plasma protein extravasation
(PPE). IN health humans, however, there are regularly too few SP containing C fibers for PPE. In CRPS, however, significant PPE could be shown in almost all patients investigated. In contrast to the flare response this increased PPE was limited to the affected side. These results so far suggested two possible pathomechanisms leading to facilitated neurogenic inflammation in CRPS--either increased release or hampered inactivation of neuropeptides. In order to further unravel this mechanisms we perfused SP in ascending concentrations through dermal microdialysis fibers, We found SP significantly more effective to induce PPE in CRPS patients than controls. Alike increased flare, this increase responsiveness to SP was present on both the affected and unaffected limbs.

To summarize, our investigations: we found evidence that neurogenic inflammation may be essential
to explain many symptoms of CRPS. There must be a trauma-related upregulation of neuropeptide
release from primary afferents on the affected side. However, in addition, there must be constitutionally
impaired inactivation of neuropeptides which predisposes some subjects to develop CRPS in response to
limb trauma.

LONG TERM RESULTS(translation)
M van Kleef, AZ Maastricht, Dept. of Anesthesiology and Pain Management, Maastricht.

Spinal cord stimulation (SCS) has been used since 1967 for treating chronic pain patients. Since the
beginning of the 90’s it has been used to treat CRPS type 1. In 1997, AZM, compared research of the
effects of SCS with chronic pain patients and those with CRPS. From this study you can see that after one half year significant reduction in pain perception and quality of life with patients treated with SCS.

During his speech he will discuss possible mechanisms of neuropathic pain. He will also announce clinical
long term effects after 6 months, in 36 patients with subcutaneous implants they were followed. Pain scores were examined 6 months, 1 and 2 years after implantation. With all the patients there was a pain diary and quality of life was measured by scientific testing EQ5D.

The result was that the pain was clearly reduced in 1 year and 2 years after implantation. There was still
significant reduction of VAS score. 42% of CRPS type 1 in UE and 47% of CRPS I LE reported that since the beginning of treatment they were much improved. Also the quality of life scale was clearly improved after treatment. In conclusion SCS pain intensity with majority of patients with CRPS-I reduced pain and quality of life improved. No significant difference in outcome between patients with cervical or lumbar SCS.

EC Covington, Cleveland Clinic Foundation, Pain Rehabilitation Program, Cleveland Ohio USA

Historically, CRPS has been strongly associated with psychological disorder and several relationships have been proposed: 1) CRPS is a psychiatric (somatoform/conversion) disorder; 2) psychiatric
illness/personality disorder create a predisposition to the development of CRPS; 3) CRPS causes
psychiatric illness; 4) psychological factors modify the course of CRPS and 5) adjustment and function in
CRPS are determined by psychological factors. These ideas derived from the obscure nature of the disease and the marked discordance between the often trivial injury and the severity of complaints and spread of symptoms. It is also likely that failures of coping and adaptation are disproportionately represented among intractable cases, and that patients in pain centers (where CRPS has been studied) have more psychopathology than those in the community.

The myth of CRPS as a psychogenic condition has faded in the face of substantial evidence that the
psychopathology in these patients does not differ appreciably from that in others with chronic pain. It has
been further weakened by studies showing genetic determinants of that illness and evidence of central
reorganization with thalamic and cortical changes.

One origin of the myth of psychogenicity in CRPS may be that the condition is relatively easy to simulate.
Several patients with “typical RSD” had clear evidence of a ligature on the arm or leg. Less obvious cases of self-inflicted disease or exacerbation have involved prolonged dependency and forced abnormal
posturing. These conditions constitute “faux CRPS” and the patients are profoundly psychiatrically

The major sequela of CRPS is depression. Axis II disorders are reportedly common as well; however,
severe pain and disability produce such profound changes in “personality” that these disorders are
probably not true personality disorders, but maladaptive attitudinal and behavioural responses
induced by the disease. A psychophysiologic component to CRPS is suggested by the studies of
stress at onset and by the fact that autonomic arousal increase its symptoms.

The influence of behavioral factors on the course of CRPS is suggested by the fact that disuse produces a
clinical picture similar to that of CRPS. and exercise and mobilization have been shown to reverse edema,
trophic changes and vasomotor signs.

Cognitive factors are likely to play a role in the person’s ability to cope with the pain of CRPS and issues
of gain/reinforcement/reward influence coping behaviour as well.

While psychological issues do not explain CRPS, they do play a major role in its treatment and in the
response to such invasive treatments as spinal cord stimulation. Cognitive therapies and interventions
focused on improved physiologic self regulation (biofeedback training, autogenic training, self hypnosis)
are most important. Formal behaviour modification may be required to assist the difficult patient to initiate
a recovery program and family members must be partners in this endeavor.

Multidisciplinary pain rehabilitation, with simultaneous focus on symptom control, physical rehabilitation,
psychotherapy and behavioral management is probably the best option for patients who fail less extensive

Lecture notes:

There is no such thing as an RSD personality. There is no personality for asthma or migraine either.
Extreme behaviour after a minor injury is questioned by doctors. They take the attitude: “If I can’t see it, it does not exist”. Since there is no single test for CRPS, “if I can’t explain it with evidence, then it does not exist”. This is an inaccurate conclusion from tertiary care doctors.

There is no difference between CRPS and lower back pain patients. CRPS patients were less depressed and scored lower on hysteria in a recent study.

The mind plays a role in suffering: we either cope or do not adapt. What is a personality? We think, feel
and behave. An irritable bladder or bowel or chest pain is not perceived as psychogenic, why should

With visceral CPRS in the organs ie. bladder, bowel etc. those with high anxiety develop visceral
hyperalgesia easily. ( Gunter 2000.)

“Limbically augmented pain syndrome” is a sensitization process in some chronic pain patients where loud
noises result in seizures. Also “polymodial allodynia” is where the noise causes pain or trauma and
psychological stress. (Rome Pain Med 2000)

Suffering is the emotional part of pain. In pain centers the most common is anxiety. In 104 CRPS patients, 96% suffer from chronic depression. (Rudy,TE Pain 1988) there is a definite link between pain and depression. It needs interference to break the link e.g. a control factor like therapy.
In lower extremity CRPS 79.2% experienced major stress at the onset of CRPS. Therefore, we can
conclude that high stress predisposes someone to CRPS.

In behaviour, the stigma of CRPS is that patients are “poorly motivated to get well and they do not make
the effort”. Active exercise can reverse edema and disuse is detrimental. Cognition and pain lead to
misinformation e.g. that pain means body damage and that they are helpless and fragile. This leads to
inactivity which results in deconditioning and it becomes a cycle of pain and disability.

Learned helplessness is found in many chronic pain patients. You are not fragile or powerless. We need to empower them and give them a sense of control. Good behaviour should be rewarded. Immediate
consequences: if it feels good now it may be bad for you later. ie. resting too much and not exercising

Many chronic pain patients do not do well in treatment if they continue to look for who is at fault. They
will have a poor response to treatment and blame is toxic.

There is no data on “psuedo-CRPS” like ligatures, forced dependency or posture. Doctors need to make
the correct diagnosis.

“Chronic pain changes who you are”. Stress can make CRPS worse. It is rare that it is self-induced. There is cross talk between nerves: emotional allodynia cause organic allodynia.

Prof WAA Zuurmond, University of Amsterdam, Amsterdam.

CRPS is a complication that can occur after a trauma or operation to an extremity. Patients can become
quite disabled, to losing total function in an affected extremity. Not everyone develops CRPS after a
trauma or operation. Why is this complication in one patient and not in another?

The symptoms of CRPS resemble an exaggerated inflammatory reaction. Could CRPS be the result of an
exaggerated inflammatory response from an anti stress or anti-immune reaction?

Lecture notes:
CRPS is neurogenic inflammation. Is it an auto-immune response? Many diseases have HLA factors e.g.
MS. Is HLA the initiator in CRPS? Is the modulator TNF? The HLA molecule has various parts A and B.

Method: A control group of 1,000 and 161 CRPS patients were typed for HLA A and B. then TNF-a using PCR-SSP-SSO-ELISA typing. Results were:


Type CRPS-1 patients Control Group
HLA-DR 6(cold RSD) 50% 31%
HLA-DQ 1(warmRSD) 99% 83%
TNF-a 40% 19%
Subgroup(more than one extremity) 50% 31%


Patients in subgroup have HLA-TNF-a2 association. This result needs research on treatments that will have an effect on TNF-a.

*from Dutch Conference handouts and lecture notes from attendees. Special thanks to Marijn Birnie for translations.


Berde CB,Lee BH, Scharff L, Sethna NF, McCarthy CF, Scott-Sutherland J, Shea AM, Sullivan P, Meier P, Zurakowski D, Masek BJ.Physical therapy and cognitive-behavioral treatment for complex regional pain syndromes. J Pediatr 2002 Jul;141(1):135-40 Pain Treatment Service and the Departments of Physical Therapy, Orthopaedic Surgery, and Psychiatry, Children's Hospital, Boston, Massachusetts.

Complex regional pain syndromes (CRPS; type 1, reflex sympathetic dystrophy, and type 2, causalgia) involve persistent pain, allodynia, and vasomotor signs. We conducted a prospective, randomized, single-blind trial of physical therapy (PT) and cognitive-behavioral treatment for children and adolescents with CRPS. Children 8 to 17 years of age (n = 28) were randomly assigned to either group A (PT once per week for 6 weeks) or group B (PT 3 times per week for 6 weeks). Both groups received 6 sessions of cognitive-behavioral treatment. Assessments of pain and function were repeated at two follow-up time periods. Outcomes were compared at the three time points through the use of parametric or non parametric analysis of variance and post hoc tests. All five measures of pain and function improved significantly in both groups after treatment, with sustained benefit evident in the majority of patients at long-term follow-up. Recurrent episodes were reported in 50% of patients, and 10 patients eventually received sympathetic blockade. Most children with CRPS showed reduced pain and improved function with a noninvasive rehabilitative treatment approach. Long-term functional outcomes were also very good.
PMID: 12091866

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 Jan;95(1-2):119-24
Department of Anesthesiology, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Suite 403-G MAB, 1211 Twenty-First Avenue South, 37232-1557, Nashville, TN, USA

This study tested for evidence supporting the clinical lore of three sequential stages of complex regional pain syndrome (CRPS) and examined the characteristics of possible CRPS subtypes. A series of 113 patients meeting IASP criteria for CRPS underwent standardized history and physical examinations to assess CRPS signs and symptoms in four domains identified in previous research: pain/sensory abnormalities, vasomotor dysfunction, edema/sudomotor dysfunction, and motor/trophic changes. K-Means cluster analysis was used to derive three relatively homogeneous CRPS patient subgroups based on similarity of sign/symptom patterns in these domains. The resulting CRPS subgroups did not differ significantly regarding pain duration as might be expected in a sequential staging model. However, the derived subgroups were statistically-distinct, and suggested three possible CRPS subtypes: (1) a relatively limited syndrome with vasomotor signs predominating, (2) a relatively limited syndrome with neuropathic pain/sensory abnormalities predominating, and (3) a florid CRPS syndrome similar to 'classic RSD' descriptions. Subtype 3 showed the highest levels of motor/trophic signs and possible disuse-related changes (osteopenia) on bone scan, despite having directionally the briefest pain duration of the three groups. EMG/NCV testing suggests that Subtype 2 may reflect CRPS-Type 2 (causalgia). Overall, these results are consistent with limited previous work that argues against three sequential stages of CRPS. However, several distinct CRPS subtypes are suggested, and these could ultimately have utility in targeting treatment more effectively.
PMID: 11790474

Graham LE, McGuigan C, Kerr S, Taggart AJ. Complex regional pain syndrome post mastectomy Orthop Ihre Grenzgeb 2001 Sep-Oct;139(5):452-7 Rheumatol Int 2002 Jan;21(4):165-6 Registrar in Rheumatology, Musgrave Park Hospital, Belfast, Northern Ireland.

Complex regional pain syndrome includes the previously termed condition reflex sympathetic dystrophy. It is a chronic pain disorder diagnosed on the basis of symptoms and skin changes and is known to have a psychological element. It is a rare complication after surgery, especially mastectomy. We present two females who developed this syndrome after undergoing mastectomy for chronic mastalgia. These cases demonstrate that amputation of an organ for chronic pain can result in reflex sympathetic dystrophy developing in a nearby limb.
PMID: 11843174


Rho RH, Brewer RP, Lamer TJ, Wilson PR Complex regional pain syndrome.Mayo Clin Proc 2002 Feb;77(2):174-80 Division of Pain Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy, is a regional, posttraumatic, neuropathic pain problem that most often affects 1 or more limbs. Like most medical conditions, early diagnosis and treatment increase the likelihood of a successful outcome. Accordingly, patients with clinical signs and symptoms of CRPS after an injury should be referred immediately to a physician with expertise in evaluating and treating this condition. Physical therapy is the cornerstone and first-line treatment for CRPS. Mild cases respond to physical therapy and physical modalities. Mild to moderate cases may require adjuvant analgesics, such as anticonvulsants and/or antidepressants. An opioid should be added to the treatment regimen if these medications do not provide sufficient analgesia to allow the patient to participate in physical therapy. Patients with moderate to severe pain and/or sympathetic dysfunction require regional anesthetic blockade to participate in physical therapy. A small percentage of patients develop refractory, chronic pain and require long-term multidisciplinary treatment, including physical therapy, psychological support, and pain-relieving measures. Pain-relieving measures include medications, sympathetic/somatic blockade, spinal cord stimulation, and spinal analgesia.
PMID: 11838651

Weber M, Neundorfer B, Birklein F. Sudeck's atrophy: pathophysiology and treatment of a complex pain syndrome Dtsch Med Wochenschr 2002 Feb 22;127(8):384-9 Neurologische Klinik (Direktor: Prof. Dr. B. Neundorfer), Friedrich-Alexander-Universitat Erlangen.

Sudeck's atrophy: pathophysiology and treatment of a complex pain syndrome. SUMMARY: The "Morbus Sudeck" or Complex Regional Pain Syndrome (CRPS) forms a typical triad of motor, sensory and autonomic symptoms. It is clinically characterized by spontaneous pain and hyperalgesia not limited to a single nerve territory and disproportionate to the inciting event. An underlying pathophysiology which could explain the whole symptomatology of CRPS is still unknown. Therefore, nowadays therapy is still symptomatic. However, recent research led to a better understanding of the disease and to the beginning of a pathophysiologically orientated therapy.
PMID: 11859448

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 Jan-Feb;27(1):90-3 Department of Anesthesiology and Critical Care Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131-5216, USA.

BACKGROUND AND OBJECTIVES: We present 2 case reports that illustrate that chronic intrathecal (IT) baclofen administration may be efficacious in treating patients with long-standing complex regional pain syndrome, type I (CRPS I) who have failed treatment with multiple drugs and procedures.
CASE REPORTS: Both cases presented were women who developed CRPS I following multiple lower extremity surgeries. One patient had had symptoms for 5 years and had continued symptoms despite multiple sympathetic blocks, sympathectomy, spinal cord stimulation, and various medication trials. The other patient had had chronic lower extremity pain for 30 years and symptoms of CRPS for about 5 years. Her symptoms continued despite multiple sympathetic blocks, sympathectomy, and many medications. Neither patient had motor dysfunction (dystonia, tremors, spasticity) associated with their painful disorder. One patient experienced good control of pain, allodynia, and autonomic dysfunction with a combination of IT baclofen and clonidine after failing treatment with IT morphine. Baclofen alone produced intolerable side effects at the doses required to produce adequate analgesia. The other patient experienced long-term control of pain, allodynia, and autonomic symptoms with IT baclofen alone.
CONCLUSIONS: IT baclofen appears to be an option for patients with intractable CRPS who have failed other modalities, including IT morphine.

IASP (International Association for the Study of Pain) Congress
San Diego, CA
August 15, 2002.

The following studies will be presented at this congress. Many of these studies are being developed as new treatment options for CRPS.
Studies are listed by abstract number.

Abstract ID: 1218-P134
M. Imamura1, S.T. Imamura1, A.A. Fischer2, D.A. Cassius3, A.E. Carvalho Jr1 1 Division of Physical Medicine, Foot Clinic, Dept. Orthopaedics and Traumatology, University of So Paulo, São Paulo, Brazil , 2 Mount Sinai School of Medicine, New York, NY , 3 Moss Bay Center, Seattle, WA

Aim of Investigation: To evaluate improved techniques for examination and treatment of CRPS of the lower limbs.
Methods: Fourteen adult patients with CRPS I (12) and II (2) of the lower limbs, of various etiologies, for mean duration of 14.6 months were evaluated. Patients were tested for dermatomal hyperalgesia by a skin scratch test, pinching and rolling the skin, and electric skin conductance. Myotomal hyperalgesia was evaluated based on the presence of muscle spasm, taut bands, trigger points (TrPs) and tender spots (TSs). All patients received tricyclic antidepressants, neuroleptics, non- steroidal anti-inflammatory drugs, analgesics and a functional rehabilitation pro gram. Treatment was combined with paraspinous blocks, pre injection blocks and needling and infiltration of taut bands, TrPs and TSs, when a segmental sensitization was diagnosed. Pain intensity was evaluated by visual analog scale (VAS) before and after treatment.
Results: VAS values reduced (p=0.002) from 9.11.4 to 5.12.7 with treatment. The dermatomal hyperalgesia present prior to treatment was reduced towards normalization. Spasm and TrPs in the corresponding myotome became less tender. A segmental distribution of sensitization was noted at multiple (2-3) levels in 85.7% of the patients.
Conclusions: Improved examination techniques showed that pain in CRPS is frequently manifested as a sensitization in a spinal segmental distribution. By treating the spinal segmental sensitization, CRPS patients had a significant reduction in their pain intensity.

Abstract ID: 1217-P133
L.L. Brown, M. Stanton-Hicks Pain Management Center, Cleveland Clinic Foundation, Cleveland, OH

Aim of Investigation: To report the occurrence of complex regional pain syndrome in a set of identical twin sisters. To review the literature and to discuss the contribution of this case to the growing body of evidence suggesting a genetic influence in the development of complex regional pain syndrome.
Methods: Chart review was conducted for two identical twin sisters. History of original injury, disease progression and response to diagnostic and therapeutic procedures is reported.
Results: Identical twin sisters, aged 36, both sustained work related injuries to their right ulnar nerves that progressed to complex regional pain syndrome. Original evaluations, including radiographs, electromyelograms, and nerve conduction studies were normal. After a prolonged course of various failed therapeutic modalities, Twin A had a peripheral nerve stimulator implanted. Twin B is currently receiving a course of bier block treatments awaiting approval for a peripheral nerve stimulator.
Conclusions: A linkage between neuropathic pain and a single autosomal recessive gene has been demonstrated in mice.1 Further work has suggested an HLA antigen association with complex regional pain syndrome.2,3 This is the first case report of complex regional pain syndrome existing in human identical twins. The development of symptoms in the same limb further lends support to a potential genetic component predisposing one to this chronic neuropathic pain state.
Key Words: complex regional pain syndrome; reflex sympathetic dystrophy; heredity; MHC-HLA References: 1. Devor M, Raber P. Pain, 42,1990, 51-67. 2. Kemler MA. Neurology, 53, 1999, 1350-51. 3. Mailis A, Wade J. Clin Jrnl Pain, 10(3), 1994, 210-17.


Abstract ID: 1216-P132
R. Casale1, T. Savarin2, S. Pieropan2, P. Mazzi2, B. Sommovigo3 1 Clin. Neurophysiology, "S.Maugeri" Found. Rehabil. Institute, Montescano (PV), Italy , 2 Dept. Internal Med., Univ. of Verona, Verona, Italy , 3 European School of MCR, Pavia, Italy

Introduction. Pain from myocardial infarction (MI) can be referred to superficial and deep somatic structures and also generate skin-referred trophic changes. Connective tissue massage is a physiotherapeutic technique consisting in the recognition of specific areas of dorsal cutaneous altered trophism, empirically related to the presence of visceral pathologies, the lateral subscapular cutaneous area (SSCA) being related to cardiac diseases. The aim of this preliminary study was to determine whether MI positively correlates with trophic alterations in SSCA.
Methods. 24 consecutive non-randomized pts (8M; 16M mean age 41) referred to an Emergency Unit for chest pain were studied. Immediately after the clinical stabilization, independent observers scored the presence or absence of SSCR. Troponin (TP) levels (TP<0.1mg/ml = normal, TP>3 mg/ml = myocardial necrosis) were recorded by other independent observers. Results. 7 out of 24 patients had a final diagnosis of a painful cardiac disease with increased TP levels (6 MI, 1 myocarditis): 6 had SSCA trophic changes. 17 had a generic diagnosis of chest pain of non-cardiac origin: only 5 had positive SSCA changes. (Fisher's test: p = 0.023; Sensitivity = 6/7 = 86%; Specificity = 12/17 = 71%; Positive predictive value = 6/11 = 54%; Negative predictive value = 12/13 = 92%).
Conclusion. Trophic changes in SSCA positively and statistically correlate with biohumoral indices of MI pointing out that acute cardiac pain due to MI can acutely induce skin-referred trophic changes. The absence of trophic changes also has a relevant predictive value in detecting non-cardiac pain (92%).

Abstract ID: 1215-P131
B. Pleger1, P. Schwenkreis1, F. Janssen1, O. Rommel1, P. Ragert1, B. Vlker2, C. Maier2, M. Zenz2, M. Tegenthoff1
1 Neurology, Kliniken Bergmannsheil, Ruhr-University, Bochum, Germany , 2 Anaesthesiology, Kliniken Bergmannsheil, Ruhr-University, Bochum, Germany

Aim of Investigation: In the case of CRPS, the involvement of the central nervous system in the development of pain stays unsolved. The aim of this study was to determine, if there are pain-correlated representational changes of the somatosensory cortex in CRPS.
Methods: We performed a SSEP mapping in 7 patients with CRPS I of one upper limb with electrical stimulation of the median and ulnar nerve to get an idea of the magnitude of hands representational field.
Results: We found a significant smaller Euclidean distance between the median and the ulnar nerve N20-dipole localizations of the somatosensory cortex contralateral to the CRPS-affected limb. The difference between the polar angels of the N20-dipole localizations of both nerve representations mirrored a smaller representational field of the CRPS-affected hand. The mean pain value was correlated with the changes of the corresponding representational field of the affected limb. Little actual pain was associated with small changes of the representational field, while subjects with large cortical reorganization complained high pain levels.
Conclusions: Cortical reorganization processes of hands` representational field seem to be closely related to the amount of nociceptive processing. Probably, pain-related thalamic hyperactivity leading to a disturbed input in post-connected somatosensory pathways might explain our findings of a smaller cortical representation area of the CRPS-affected hand.

Abstract ID: 1214-P130
L. Demartini1, R. Bettaglio1, M. Allegri1, G. Bonetti1, A. Violini1, A. Braschi2, A. Nava1 1 palliative care and pain therapy, Fondazione Maugeri, Pavia, Italy , 2 anesthesia and intensive care institute, Pavia's University, Pavia, Italy

Aim of investigation: We planned a study to evaluate the short and long term efficacy of regional sympathetic blockade with guanethidine in patients with CRPS with pain scales (Neuropathic Pain Scale and Brief Pain Inventory).
Methods: Since January 2001 we enrolled 17 patients fulfilling the IASP criteria for CRPS. All of them were studied with bone scintigraph, telethermography and TcPO2 to evaluate vasomotor changes, QST and von Frey needling for sensory changes; NPS and BPI were applied. A great majority of patients had already received other treatments prior to the study with no or poor effect. The patients were treated with a course (six) of regional sympathetic blockades according to the technique of Hannington-Kiff and then they were revalued. When pain and impairment improved but still persisted the patients underwent another course of blockades and were then revalued.
Results: The NPS values, after treatment (first course), show a significant reduction in all items, specially pain intensity (from 7.23 to 3.17); deep pain intensity (from 7.64 to 3.83) improves more than surface pain intensity (from 3.76 to 2.47). BPI values show a reduction not only of pain intensity but also of functional impairment in daily living (from 7.82 to 3.58) and sleep (from 5.86 to 1.88).
Conclusions: Pain has various mechanisms in CRPS. With this study it seems that regional sympathetic blockade is not only effective on pain but also (specially) on functional impairment. We saw improvement of edema and joint movement before reduction of pain. These data justify further evaluation.

Abstract ID: 1213-P129
G.P. Dureja, T. Jayalakshmi, B. Ghai, S. Prakash, H.L. Kaul Pain Clinic, All India Inst of Med Sciences, New Delhi, India

AIM OF INVESTIGATION: To evaluate three different therapeutic modalities for management of CRPS Type I of upper extremities in a randomized prospective clinical trial.
METHODS: Sixty-four consecutive patients with CRPS-I of upper extremity were the subjects of this study. After a clinical evaluation for diagnostic criterion of CRPS-I, a 3-Phase Bone Scan was done to confirm the diagnosis. The patients were then randomly assigned to receive either stellate ganglion blocks with 10 ml of 0.25% Bupivacaine on alternate days for a maximum of 10 blocks (Group A, n=23) or, IVRA with 1.5 mg/kg Bretylium and 10 mg lidocaine (30 ml volume) repeated twice at 15 days interval (Group B, n=21) or, IVRA with 0.3 mg/kg Guanethidine and 10 mg lidocaine (30 ml volume) (Group C, n=20) repeated twice at 15 days interval. Various objective parameters evaluated included digital plethysmography, telethermometry, doppler flowmetry and scoring of Pain relief, edema and range of motion on a 0-10 score. Minimum follow up duration was 6 months and complete pain relief and functional improvement was considered as successful outcome.
RESULTS: IVRA with Bretylium resulted in an earliest (mean 6.3 days) and maximum relief in pain (VAS <3), and functional parameters in 20 out of 23 patients (P<0.01). Intermittent stellate ganglion blocks provided relief in pain (VAS<5) and functional parameters in 15/21 patients. IVR block with Guanethidine was least effective and only 3 out of 20 patients had acceptable pain relief.
CONCLUSIONS: Intravenous regional block with Bretylium resulted in a successful outcome in 86.8% patients with CRPS-I.

Abstract ID: 1212-P128
R.J. Verdugo, L.A. Bell, M. Campero, F. Salvat, B. Tripplet, J. Sonnad, J.L. Ochoa Oregon Nerve Center, OHSU, Portland, OR

Aim of Investigation: To discern patterns of hyperalgesias/allodynias in CRPS I and II and to investigate their pathophysiological natures.
Methods: 132 patients with CRPS I and II underwent neurological and neurophysiological evaluation following a standard clinical protocol and conventional nerve conduction, electromyography, somatosensory evoked potentials, transcranial magnetic stimulation, quantitative somatosensory thermotest, infrared telethermography, and placebo-controlled somatic and sympathetic nerve blocks.
Results: Two distinct semeiologic entities surfaced; classic neurological vs. atypical, fulfilling the description of CRPS II and I respectively. The CRPS II group (34.9%) exhibited sensory-motor patterns restricted to the anatomical distribution of nerves and spinal roots and had evidence of peripheral nerve pathology. The CRPS I group (65.1%) departed from the laws of anatomy, physiology and pathology. They had physiological normality of central and peripheral motor and sensory pathways and abundant psychogenic signs.
Conclusions: These different clinical-physiological characteristics of hyperalgesias/allodynias signal either psychogenic dysfunction or structural pathology. These findings question the dictum that tactile allodynia signals central neuronal sensitization. The historical argument, when re-examined under evidence-based standards yields contradiction and gratuitous extrapolation. The refractoriness of a many neuropathic pain patients to hypothesis-driven, invasive, or addictive therapy, betrays current misinterpretation of their authentic neuropathogical and psychopathological origins, while highlighting the iatrogenic connotation of the present paradigm.
Acknowledgement: Supported NIH grant NS 39761.


Abstract ID: 1211-P127
A. Ploppa1, R.T. Kiefer1, B. Noh1, P. Rohr2, J. Grothusen3, L. Distler4, H.J. Dieterich1, K. Unertl1, R.J. Schwartzman3
1 Anesthesiology, Eberhard-Karls University, Tuebingen, Germany , 2 Anesthesiology, Klinikum Saarbruecken, Saarbruecken, Germany , 3 Neurology, MCP-Hahnemann University, Philadelphia, PA , 4 Pain Therapy, Caritasklinik St.Theresia, Saarbruecken, Germany

Aim of investigation: To detect and monitor changes in skin blood flow during experimental high dose ketamine-midazolam anesthesia for intractable cases of CRPS-I by Laser Doppler Flowmetry (LDF).
Methods: Patients suffering from therapy-refractory CRPS I (duration: 4 months-6 years) received ketamine-midazolam anesthesia over 5 days. Skin perfusion was determined by LDF (Perimed, PF 4100) on D-II and radial forearm. In one patient with severe allodynia at the upper arm this area and D-II were measured.
Results:Significantly decreased skin perfusion seems to occur in late stages with manifest atrophic and dystrophic signs. Under ketamine anesthesia, a significant increase in skin blood flow was observed (clinical correlate: hyperemia, edema) in the first 72 hours. Areas of maximal allodynia showed the strongest increase in blood perfusion (up to ten-fold, p<0.05). The highest increment in skin blood flow was observed in patients with dystrophy and atrophy. During the following days, normalization of skin blood flow and regaining vasomotor activity were observed (clinical correlate: decrease of swelling, hyperemia, temperature changes).
Conclusions: LDF might be a valid and noninvasive method to monitor skin perfusion changes and potentially success of therapeutic procedures for CRPS I. Further evidence is needed to qualify and quantify regained vasomotive activity as indicator of effective CRPS-I therapy.

Abstract ID: 1210-P126
R.T. Kiefer1, P. Rohr2, A. Ploppa1, H.J. Dieterich1, K.H. Altemeyer2, J. Grothusen3, K. Unertl1, R.J. Schwartzman3
1 Anesthesiology, Eberhard-Karls University, Tuebingen, Germany , 2 Anesthesiology, Klinikum Saarbruecken, Saarbruecken, Germany , 3 Neurology, MCP-Hahnemann University, Philadelphia, PA

Aim of Investigation: Sufficient pain relief for Complex Regional Pain Syndrome Type I (CRPS-I/RSD) remains challenging. Accumulating evidence points to the involvement of sensitized central pain projecting neurons by NMDA-receptor activation. This evidence is the rationale for prolonged NMDA-blockade with ketamine in intractable CRPS-I patients.
Methods: Six patients with steadily worsening CRPS-I, who failed all standard medical and sympatholytic treatment, were anesthesized in the ICU's of hospitals in Tuebingen and Saarbruecken, Germany. Treatment was initiated by bolus injections of ketamine (0.5mg/kg) and midazolam (2.5-5mg) until deep sedation (Ramsay Score 4-5)was reached.Therapy was maintained with infusions of ketamine (3-7mg/kg/h) and midazolam (0.15-0.3mg/kg/h) over five days. On the fifth day infusions were slowly tapered. 3 patients did not require intubation and 3 were pre-emptively intubated (1 for increased aspiration risk, 2 due to respiratory infection).
Results: Six patients underwent treatment without significant complications. All showed an excellent immediate response and were pain free and without spontaneous or touch evoked allodynia or hyperalgesia. One patient has remained completely pain free for more than 2 years. Five of the six patients had return of the pain of the original injury, but are relieved of the hyperalgesia, mechanical and thermo-allodynia and swelling in the affected areas.
Conclusions: Prolonged ketamine-midazolam anesthesia shows promise as an effective therapeutic option for severe and otherwise intractable cases of CRPS-I.

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