CRPS Research Update November 2012

Welcome to the research update where you can read about the latest studies in complex regional pain syndrome. We are dedicated to raining the awareness of CRPS and bringing the latest thinking in science into the clinic to treat pain.

For new readers, our clinics in London and Surrey specialise in the treatment of complex regional pain syndrome (CRPS/RSD) – click here for details: Specialist Pain Physio Clinics.

We welcome your comments about the research and your own experiences of CRPS.


Eur J Pain. 2012 Nov 7. doi: 10.1002/j.1532-2149.2012.00213.x. [Epub ahead of print]

Clinical evidence of parietal cortex dysfunction and correlation with extent of allodynia in CRPS type 1.


Royal National Orthopaedic Hospital, Stanmore, UK; The Royal National Hospital for Rheumatic Diseases, Bath, UK; University of Bath, UK.



Unusual symptoms such as digit misidentification and neglect-like phenomena have been reported in complex regional pain syndrome (CRPS), which we hypothesized could be explained by parietal lobe dysfunction.


Twenty-two patients with chronic CRPS attending an in-patient rehabilitation programme underwent standard neurological examination followed by clinical assessment of parietal lobe function and detailed sensory testing.


Fifteen (68%) patients had evidence of parietal lobe dysfunction. Six (27%) subjects failed six or more test categories and demonstrated new clinical signs consistent with their parietal testing impairments, which were impacting significantly on activities of daily living. A higher incidence was noted in subjects with >1 limb involvement, CRPS affecting the dominant side and in left-handed subjects. Eighteen patients (82%) had mechanical allodynia covering 3-57.5% of the body surface area. Allochiria (unilateral tactile stimulation perceived only in the analogous location on the opposite limb), sensory extinction (concurrent bilateral tactile stimulation perceived only in one limb), referred sensations (unilateral tactile stimulation perceived concurrently in another discrete body area) and dysynchiria (unilateral non-noxious tactile stimulation perceived bilaterally as noxious) were present in some patients. Greater extent of body surface allodynia was correlated with worse parietal function (Spearman’s rho = -0.674, p = 0.001).


In patients with chronic CRPS, detailed clinical examination may reveal parietal dysfunction, with severity relating to the extent of allodynia.


Ann Nucl Med. 2012 Oct;26(8):665-9. doi: 10.1007/s12149-012-0623-2. Epub 2012 Jul 14.

Is there a correlation between symptoms and bone scintigraphic findings in patients with complex regional pain syndrome?

Alsharif A, Akel AY, Sheikh-Ali RF, Juweid ME, Hawamdeh ZM, Ajlouni JM, Abdulsahib AS, Alhadidi FA, Elhadidy ST.


Nuclear Medicine Section, Radiology and Nuclear Medicine Department, Faculty of Medicine, Jordan University Hospital, University of Jordan, Queen Rania Street, Al-Jubeiha, P.O.Box 13046, 11942, Amman, Jordan,



Complex regional pain syndrome (CRPS) is characterized by pain in combination with sensory, vasomotor, sudomotor, trophic and motor abnormalities. The diagnosis of CRPS is based primarily on clinical criteria and the presence of distinct signs and symptoms. The role of bone scintigraphy in the diagnosis of these patients has been limited by its variable sensitivity. In this study, we aim to look if the presence of specific symptoms or symptom subgroups in patients with clinically diagnosed CRPS correlates with scintigraphic findings in bone scan.


We retrospectively reviewed clinical records of patients referred for bone scintigraphy with the clinical diagnosis of CRPS during the period December 2006 until February 2011. Patients were classified into 4 distinct subgroups according to the presence of specific symptoms namely sensory subgroup, sudomotor and/or edema subgroup, vasomotor subgroup and finally motor and/or trophic changes subgroup. We looked specifically for the correlation between these specific symptoms and scintigraphic bone findings.


37 patients were referred for bone scintigraphy with the clinical diagnosis of CRPS and were enrolled in the study. The presence of vasomotor symptoms and (motor and/or trophic changes) was significantly higher in patients with positive bone scintigraphy (P value 0.0133, 0.018 respectively). There was no other statistically significant correlation between the presence of specific symptoms or symptom subgroups on one hand and the result of bone scintigraphy on the other hand.


The probability of positive bone scintigraphy increased significantly in patients with vasomotor symptoms and in patients with motor and/or trophic changes. This may contribute to the reported variability of the diagnostic performance of bone scintigraphy in CRPS patients.


J Neuroimmune Pharmacol. 2012 Oct 11. [Epub ahead of print]

Imaging and Clinical Evidence of Sensorimotor Problems in CRPS: Utilizing Novel Treatment Approaches.

Bailey J, Nelson S, Lewis J, McCabe CS.


Bath Centre for Pain Services, The Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath, BA1 1RL, UK.


Inflammation and altered autonomic function are diagnostic signs and symptoms of Complex Regional Pain Syndrome. In the acute stages these are commonly at their most florid accompanied by severe pain and reduced function. Understandably this has directed research towards potential peripheral drivers for the causal mechanisms of this condition. In particular this is now focused on the inflammatory process and the potential role of autoantibodies. More subtle changes also occur in terms of altered tactile processing within the affected limb, disturbances in body perception and motor planning problems that become more evident as the condition progresses. Through careful clinical observation and neuro-imaging techniques, these changes are now thought to be associated with altered cortical processing that includes reorganisation of both the motor and sensory maps. Furthermore, there appears to be a close relationship between the intensity of pain experienced and the extent of cortical re-organisation. This increased knowledge around the peripheral and central mechanisms that may be operating in CRPS has been used to inform novel therapeutic approaches. We discuss here the presenting signs and symptoms of CRPS, with particular focus on sensory and motor changes and consider which mechanisms may drive these changes. Finally, we consider the emerging therapeutic options designed to correct these aberrant mechanisms.


Eur J Pain. 2012 Oct 5. doi: 10.1002/j.1532-2149.2012.00217.x. [Epub ahead of print]

Treatment of complex regional pain syndrome in adults: A systematic review of randomized controlled trials published from June 2000 to April 2010.

Cossins L, Okell RW, Cameron H, Simpson B, Poole HM, Goebel A.


Pain Research Institute, Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK.


Complex regional pain syndrome (CRPS) is a disabling pain condition with sensory, motor and autonomic manifestations. Uncertainty remains about how CRPS can be effectively managed. We conducted a systematic review of randomized controlled trials (RCTs) for treatment and prophylactic interventions for CRPS published during the period 2000-2012, building on previous work by another group reviewing the period 1966-2000. Bibliographic database searches identified 173 papers which were filtered by three reviewers. This process generated 29 trials suitable for further analysis, each of which was reviewed and scored by two independent reviewers for methodological quality using a 15-item checklist. A number of novel and potentially effective treatments were investigated. Analysing the results from both review periods in combination, there was a steep rise in the number of published RCTs per review decade. There is evidence for the efficacy of 10 treatments (3× strong – bisphosphonates, repetitive transcranial magnetic stimulation and graded motor imagery, 1× moderate and 6× limited evidence), and against the efficacy of 15 treatments (1× strong, 1× moderate and ×13 limited). The heterogeneity of trialled interventions and the pilot nature of many trials militate against drawing clear conclusions about the clinical usefulness of most interventions. This and the observed phenomenon of excellent responses in CRPS subgroups would support the case for a network- and multi-centre approach in the conduct of future clinical trials. Most published trials in CRPS are small with a short follow-up period, although several novel interventions investigated from 2000 to 2012 appear promising.


J Foot Ankle Surg. 2012 Sep 15. pii: S1067-2516(12)00392-4. doi: 10.1053/j.jfas.2012.08.003. [Epub ahead of print]

Efficacy and Safety of High-dose Vitamin C on Complex Regional Pain Syndrome in Extremity Trauma and Surgery-Systematic Review and Meta-Analysis.

Shibuya N, Humphers JM, Agarwal MR, Jupiter DC.


Associate Professor of Surgery, Texas A&M Health and Science Center, College of Medicine; Acting Chief, Section of Podiatry, Department of Surgery, Central Texas VA Health Care System; Staff, Scott and White Memorial Hospital and Clinics, Temple, TX. Electronic address:


Complex regional pain syndrome (CRPS) is a devastating condition often seen after foot and ankle injury and surgery. Prevention of this pathology is attractive not only to patients but also to surgeons, because the treatment of this condition can be difficult. We evaluated the effectiveness of vitamin C in preventing occurrence of CRPS in extremity trauma and surgery by systematically reviewing relevant studies. The databases used for this review included: Ovid EMBASE, Ovid MEDLINE, CINAHL, and the Cochrane Database. We searched for comparative studies that evaluated the efficacy of more than 500 mg of daily vitamin C. After screening for inclusion and exclusion criteria, we identified 4 studies that were relevant to our study question. Only 1 of these 4 studies was on foot and ankle surgery; the rest concerned the upper extremities. All 4 studies were in favor of this intervention with minimal heterogeneity (Tau(2) = 0.00). Our quantitative synthesis showed a relative risk of 0.22 (95% confidence interval = 0.12, 0.39) when daily vitamin C of at least 500 mg was initiated immediately after the extremity surgery or injury and continued for 45 to 50 days. A routine, daily administration of vitamin C may be beneficial in foot and ankle surgery or injury to avoid CRPS. Further foot and ankle specific and dose-response studies are warranted.


J Behav Med. 2012 Aug 2. [Epub ahead of print]

Pain acceptance-based coping in complex regional pain syndrome Type I: daily relations with pain intensity, activity, and mood.

Cho S, McCracken LM, Heiby EM, Moon DE, Lee JH.


Department of Psychology, Chung-Ang University, 221 Heukseok-dong, Dongjak-gu, Seoul, 156-756, Korea,


This study aimed to examine the temporal patterning of pain acceptance-based coping, activity, and mood in patients with complex regional pain syndrome Type I (CRPS-I), by using a daily diary method. A total of 30 patients with CRPS-I seeking treatment in a tertiary pain management center located in Seoul, Korea participated in the study. Multilevel random effects analyses indicated that (a) engagement in pain acceptance-based coping was significantly associated with lower same-day pain and negative mood and greater same-day activity and positive mood; (b) pain acceptance-based coping predicted increases in activity on the following day; (c) greater pain intensity was significantly associated with lower same-day pain acceptance-based coping and activity and greater same-day negative mood; and (d) pain intensity did not predict pain acceptance-based coping, activity, or mood on the following day. These findings suggest that patients with CRPS-I may benefit from responding to pain with acceptance. Further study and eventual application of this process in CRPS-I may improve upon the success of current approaches to this problem.


Pain. 2012 Nov;153(11):2174-81. doi: 10.1016/j.pain.2012.05.025. Epub 2012 Jul 28.

Impaired spatial body representation in complex regional pain syndrome type 1 (CRPS I).

Reinersmann A, Landwehrt J, Krumova EK, Ocklenburg S, Güntürkün O, Maier C.


Department of Pain Management, Ruhr-University Bochum, BG Universitätsklinikum Bergmannsheil GmbH, Bochum, Germany. Electronic address:


Recently, a shift of the visual subjective body midline (vSM), a correlate of the egocentric reference frame, towards the affected side was reported in patients with complex regional pain syndrome (CRPS). However, the specificity of this finding is as yet unclear. This study compares 24 CRPS patients to 21 patients with upper limb pain of other origin (pain control) and to 24 healthy subjects using a comprehensive test battery, including assessment of the vSM in light and dark, line bisection, hand laterality recognition, neglect-like severity symptoms, and motor impairment (disability of the arm, shoulder, and hand). Statistics: 1-way analysis of variance, t-tests, significance level: 0.05. In the dark, CRPS patients displayed a significantly larger leftward spatial bias when estimating their vSM, compared to pain controls and healthy subjects, and also reported lower motor function than pain controls. For right-affected CRPS patients only, the deviation of the vSM correlated significantly with the severity of distorted body perception. Results confirm previous findings of impaired visuospatial perception in CRPS patients, which might be the result of the involvement of supraspinal mechanisms in this pain syndrome. These mechanisms might accentuate the leftward bias that results from a right-hemispheric dominance in visuospatial processing and is known as pseudoneglect. Pseudoneglect reveals itself in the tendency to perceive the midpoint of horizontal lines or the subjective body midline left of the centre. It was observable in all 3 groups, but most pronounced in CRPS patients, which might be due to the cortical reorganisation processes associated with this syndrome.


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