CRPS Research Update 24/6/12

Clin J Pain. 2012 Jun 7. [Epub ahead of print]

A Day-hospital Approach to Treatment of Pediatric Complex Regional Pain Syndrome: Initial Functional Outcomes.



To examine clinical outcomes of an interdisciplinary day-hospital treatment program (comprised of physical, occupational, and cognitive-behavioral therapies with medical and nursing services) for pediatric complex regional pain syndrome (CRPS).


The study is a longitudinal case series of consecutive patients treated in a day-hospital pediatric pain rehabilitation program. Participants were 56 children and adolescents with ages 8 to 18 years (median=14 y) with CRPS spectrum conditions who failed to progress sufficiently with a previous outpatient and/or inpatient treatments. Patients participated in daily physical therapy, occupational therapy, and psychological treatment and received nursing and medical care as necessary. The model places equal emphasis on physical and cognitive-behavioral approaches to pain management. Median duration of stay was 3 weeks. Outcome measures included assessments of physical, occupational, and psychological functioning at program admission, discharge, and at posttreatment follow-up at a median of 10 months after discharge. Scores at discharge and follow-up were compared with measures on admission by Wilcoxon tests, paired t tests, or analysis of variance as appropriate, with corrections for multiple comparisons.


Outcomes demonstrate clinically and statistically significant improvements from admission to discharge in pain intensity (P<0.001), functional disability (P<0.001), subjective report of limb function (P<0.001), timed running (P<0.001), occupational performance (P<0.001), medication use (P<0.01), use of assistive devices (P<0.001), and emotional functioning (anxiety, P<0.001; depression, P<0.01). Functional gains were maintained or further improved at follow-up.


A day-hospital interdisciplinary rehabilitation approach seems effective in reducing disability and improving physical and emotional functioning and occupational performance among children and adolescents with CRPSs that have failed to improve with outpatient treatment.


Pain. 2012 Jul;153(7):1484-94. Epub 2012 May 30.

Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I.


Tactile acuity measured by 2-point discrimination performance is impaired in patients with complex regional pain syndrome type I (CRPS-I). This is mirrored by pain-associated shrinkage of the cortical representation of the affected limb. We investigated whether, also, more complex tactile performance assessed by a dynamic 2D-form perception task is disturbed in CRPS-I patients. Therefore, we developed a Braille-like recognition task (BT) for geometrical dot pattern identification by dynamic touch. We studied 47 healthy volunteers (Study I) and compared them to 16 CRPS-I patients (Study II). Besides recognition time and error quote of the BT, we assessed static 2-point discrimination thresholds (TPDT). In healthy subjects, the performance in the BT correlated significantly with age and TPDT. In CRPS patients, TPDT was significantly increased on the affected side compared to sex- and age-matched controls from study I (2.98±0.84mm vs 2.05±0.82mm, P<0.01). The performance in the BT was not impaired in CRPS-I patients (compared to sex- and age-matched controls from study I) and was not correlated to the TPDT. The intact 2D-form recognition ability in CRPS-I patients might be explained by intact dynamic tactile and proprioceptive functions, which appear to be uncompromised by the impaired static tactile perception, provided that the spacing of the dot pattern is above the individual tactile acuity. These intact 2D-form perception capacities may also be related to higher sensory integration functions like the visual system and intact semantic understanding, which may be spared by the cortical reorganization phenomena in CRPS-I.

RS: Those of you who have visited for treatment will be familiar with 2-point discrimination training that we do


Neurosci Lett. 2010 Dec 17;486(3):240-5. Epub 2010 Sep 29.

Left is where the L is right. Significantly delayed reaction time in limb laterality recognition in both CRPS and phantom limb pain patients.


The body schema is based on an intact cortical body representation. Its disruption is indicated by delayed reaction times (RT) and high error rates when deciding on the laterality of a pictured hand in a limb laterality recognition task. Similarities in both cortical reorganisation and disrupted body schema have been found in two different unilateral pain syndromes, one with deafferentation (phantom limb pain, PLP) and one with pain-induced dysfunction (complex regional pain syndrome, CRPS). This study aims to compare the extent of impaired laterality recognition in these two groups. Performance on a test battery for attentional performance (TAP 2.0) and on a limb laterality recognition task was evaluated in CRPS (n=12), PLP (n=12) and healthy subjects (n=38). Differences between recognising affected and unaffected hands were analysed. CRPS patients and healthy subjects additionally completed a four-day training of limb laterality recognition. Reaction time was significantly delayed in both CRPS (2278±735.7ms) and PLP (2301.3±809.3ms) compared to healthy subjects (1826.5±517.0ms), despite normal TAP values in all groups. There were no differences between recognition of affected and unaffected hands in both patient groups. Both healthy subjects and CRPS patients improved during training, but RTs of CRPS patients (1874.5±613.3ms) remain slower (p<0.01) than those of healthy subjects (1280.6±343.2ms) after four-day training. Despite different pathomechanisms, the body schema is equally disrupted in PLP and CRPS patients, uninfluenced by attention and pain and cannot be fully reversed by training alone. This suggests the involvement of complex central nervous system mechanisms in the disruption of the body schema.

RS: Familiar to those of you who are working on left/right judgements


Pain Physician. 2012 May;15(3):255-66.

Skin biopsy in complex regional pain syndrome: case series and literature review.



Accumulating experimental and clinical evidence supports the hypothesis that complex regional pain syndrome type I (CRPS-I) may be a small fiber neuropathy.


To evaluate the use of commercially available standard biopsy methods to detect intradermal axon pathology in CRPS-I, and to ascertain if these structural changes can explain quantitative sensory testing (QST) findings in CRPS-I.


Retrospective review of charts and laboratory data.


Outpatient clinic


Skin biopsies from 43 patients with CRPS-I were stained with PGP 9.5, and epidermal nerve fiber density, sweat gland nerve fiber density and morphological abnormalities were evaluated. Thirty-five patients had quantitative sensory testing.


Alterations in skin innervation were seen in approximately 20% of CRPS-I patients with commercial processing. There were no patient characteristics, including duration of disease, that predicted a decreased epidermal nerve fiber density (ENFD). There was no consistent relationship between QST changes and ENFD measured by standard commercial skin biopsy evaluation procedures.


Commercial processing of tissue does not utilize stereologic quantitative analysis of nerve fiber density. Biopsy material is utilized from a proximal and distal source only, and differences in denervation of a partial nerve territory may be missed. The functional attributes of small fibers cannot be assessed.


The negative results indicate that CRPS-I may be associated with changes in the ultramicroscopic small fiber structure that cannot be visualized with commercially available techniques. Alternatively, functional rather than structural alterations of small fibers or pathological changes at a more proximal site such as the spinal cord or brain may be responsible for the syndrome.


Curr Pharm Des. 2012 May 16. [Epub ahead of print]

Immunological Aspects of the Complex Regional Pain Syndrome (CRPS).


Limb trauma can lead to the development of a complex regional pain syndrome (CRPS). CRPS is a descriptive term of a variety of different symptoms. According to the current IASP-approved criteria, human CRPS can be diagnosed if a combination of signs is present: continuing pain and hyperalgesia, disproportionate to the initial trauma, skin temperature and colour asymmetry, sweating asymmetry, edema, decreased range of motion, and trophic changes. The diagnosis and treatment of human CRPS can be demanding and the pathophysiology underlying the disease is still under investigation. Immunological aspects are considered to play an important role in the development of CRPS. The impact of elevated pro-inflammatory cytokines systemically as well as locally, increased neurogenic inflammation and auto-antibodies in the pathophysiological development of CRPS are discussed in this review.


J Neurosci. 2012 Apr 25;32(17):5747-56.

Abnormalities in hippocampal functioning with persistent pain.


Chronic pain patients exhibit increased anxiety, depression, and deficits in learning and memory. Yet how persistent pain affects the key brain area regulating these behaviors, the hippocampus, has remained minimally explored. In this study we investigated the impact of spared nerve injury (SNI) neuropathic pain in mice on hippocampal-dependent behavior and underlying cellular and molecular changes. In parallel, we measured the hippocampal volume of three groups of chronic pain patients. We found that SNI animals were unable to extinguish contextual fear and showed increased anxiety-like behavior. Additionally, SNI mice compared with Sham animals exhibited hippocampal (1) reduced extracellular signal-regulated kinase expression and phosphorylation, (2) decreased neurogenesis, and (3) altered short-term synaptic plasticity. To relate the observed hippocampal abnormalities with human chronic pain, we measured the volume of human hippocampus in chronic back pain (CBP), complex regional pain syndrome (CRPS), and osteoarthritis patients (OA). Compared with controls, CBP and CRPS, but not OA, had significantly less bilateral hippocampal volume. These results indicate that hippocampus-mediated behavior, synaptic plasticity, and neurogenesis are abnormal in neuropathic rodents. The changes may be related to the reduction in hippocampal volume we see in chronic pain patients, and these abnormalities may underlie learning and emotional deficits commonly observed in such patients.


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