#CRPS – classic papers

Some of the key research that influences my work in the clinic with CRPS patients is listed here in no particular order:

Clinical features and pathophysiology of complex regional pain syndrome

Lancet Neurol. 2011 Jul;10(7):637-48 Marinus et al.

Abstract

A complex regional pain syndrome (CRPS)-multiple system dysfunction, severe and often chronic pain, and disability-can be triggered by a minor injury, a fact that has fascinated scientists and perplexed clinicians for decades. However, substantial advances across several medical disciplines have recently improved our understanding of CRPS. Compelling evidence implicates biological pathways that underlie aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity in the clinical features of CRPS. Collectively, the evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury. Variation in susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS

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Central processing of tactile and nociceptive stimuli in complex regional pain syndrome

Clin Neurophysiol. 2008 Oct;119(10):2380-8. Epub 2008 Aug 23

Abstract

OBJECTIVE:

Patients with complex regional pain syndrome (CRPS) suffer from continuous regional limb pain and from hyperesthesia to touch and pain. To better understand the pathophysiological mechanisms underlying the hyperesthesia of CRPS patients, we investigated their cortical processing of touch and acute pain.

METHODS:

Cortical responses to tactile stimuli applied to the thumbs, index and little fingers (D1, D2, and D5) and nociceptive stimuli delivered to dorsa of the hands were recorded with a whole-scalp neuromagnetometer from eight chronic CRPS patients and from nine healthy control subjects.

RESULTS:

In the patients, primary somatosensory (SI) cortex activation to tactile stimulation of D2 was significantly stronger, and the D1-D5 distance in SI was significantly smaller for the painful hand compared to the healthy hand. The PPC activation to tactile stimulation was significantly weaker in the patients than in the control subjects. To nociceptive stimulation with equal laser energy, the secondary somatosensory (SII) cortices and posterior parietal cortex (PPC) were similarly activated in both groups. The PPC source strength correlated with the pain rating in the control subjects, but not in the patients.

CONCLUSIONS:

The enhanced SI activation in hyperesthetic CRPS patients may reflect central sensitization to touch. The decreased D1-D5 distance implies permanent changes in SI hand representations in chronic CRPS. The defective PPC activation could be associated with the neglect-like symptoms of the patients. As the SII and PPC responses were not enhanced in the CRPS patients, other brain areas are likely to contribute to the observed hyperesthesia to pain.

SIGNIFICANCE:

Our results indicate changes of somatosensory processing at cortical level in CRPS.

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Neuroimage. 2006 Aug 15;32(2):503-10. Epub 2006 Jun 6. Pleger et al.

Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome

Abstract

In the complex regional pain syndrome (CRPS), several theories proposed the existence of pathophysiological mechanisms of central origin. Recent studies highlighted a smaller representation of the CRPS-affected hand on the primary somatosensory cortex (SI) during non-painful stimulation of the affected side. We addressed the question whether reorganizational changes can also be found in the secondary somatosensory cortex (SII). Moreover, we investigated whether cortical changes might be accompanied by perceptual changes within associated skin territories. Seventeen patients with CRPS of one upper limb without the presence of peripheral nerve injuries (type I) were subjected to functional magnetic resonance imaging (fMRI) during electrical stimulation of both index fingers (IFs) in order to assess hemodynamic signals of the IF representation in SI and SII. As a marker of tactile perception, we tested 2-point discrimination thresholds on the tip of both IFs. Cortical signals within SI and SII were significantly reduced contralateral to the CRPS-affected IF as compared to the ipsilateral side and to the representation of age- and sex-matched healthy controls. In parallel, discrimination thresholds of the CRPS-affected IF were significantly higher, giving rise to an impairment of tactile perception within the corresponding skin territory. Mean sustained, but not current pain levels were correlated with the amount of sensory impairment and the reduction in signal strength. We conclude that patterns of cortical reorganization in SI and SII seem to parallel impaired tactile discrimination. Furthermore, the amount of reorganization and tactile impairment appeared to be linked to characteristics of CRPS pain.

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Eur J Neurosci. 2007 Dec;26(11):3291-302.

Assessment of sensorimotor cortical representation asymmetries and motor skills in violin players.

Source

Department of Neurology, Ruhr-University Bochum, BG-Kliniken Bergmannsheil, Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, Germany.

Abstract

As a model for use-dependent plasticity, the brains of professional musicians have been extensively studied to examine structural and functional adaptation to unique requirements of skilled performance. Here we provide a combination of data on motor performance and hand representation in the primary motor and somatosensory cortex of professional violin players, with the aim of assessing possible behavioural consequences of sensorimotor cortical asymmetries. We studied 15 healthy right-handed professional violin players and 35 healthy nonmusician controls. Motor and somatosensory cortex asymmetry was assessed by recording the motor output map after transcranial magnetic stimulation from a small hand muscle, and by dipole source localization of somatosensory evoked potentials after electrical stimulation of the median and ulnar nerves. Motor performance was examined using a series of standardized motor tasks covering different aspects of hand function. Violin players showed a significant right-larger-than-left asymmetry of the motor and somatosensory cortex, whereas nonmusician controls showed no significant interhemispheric difference. The amount of asymmetry in the motor and somatosensory cortices of musicians was significantly correlated. At the behavioural level, motor performance did not significantly differ between musicians and nonmusicians. The results support a use-dependent enlargement of the left hand representation in the sensorimotor cortex of violin players. However, these cortical asymmetries were not paralleled by accompanying altered asymmetries at a behavioural level, suggesting that the reorganisation might be task-specific and does not lead to improved motor abilities in general.

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Brain. 2007 Oct;130(Pt 10):2671-87. Epub 2007 Jun 15.

The motor system shows adaptive changes in complex regional pain syndrome.

Source

Department of Neurology, Institute for Physiology and Experimental Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany. christian.maihoefner@uk-erlangen.de

Abstract

The complex regional pain syndrome (CRPS) is a disabling neuropathic pain condition that may develop following injuries of the extremities. In the present study we sought to characterize motor dysfunction in CRPS patients using kinematic analysis and functional imaging investigations on the cerebral representation of finger movements. Firstly, 10 patients and 12 healthy control subjects were investigated in a kinematic analysis assessing possible changes of movement patterns during target reaching and grasping. Compared to controls, CRPS patients particularly showed a significant prolongation of the target phase in this paradigm. The pattern of motor impairment was consistent with a disturbed integration of visual and proprioceptive inputs in the posterior parietal cortex. Secondly, we used functional MRI (fMRI) and investigated cortical activations during tapping movements of the CRPS-affected hand in 12 patients compared to healthy controls (n = 12). During finger tapping of the affected extremity, CRPS patients showed a significant reorganization of central motor circuits, with an increased activation of primary motor and supplementary motor cortices (SMA). Furthermore, the ipsilateral motor cortex showed a markedly increased activation. When the individual amount of motor impairment was introduced as regressor in the fMRI analysis, we were able to demonstrate that activations of the posterior parietal cortices (i.e. areas within the intraparietal sulcus), SMA and primary motor cortex were correlated with the extent of motor dysfunction. In summary, the results of this study suggest that substantial adaptive changes within the central nervous system may contribute to motor symptoms in CRPS.

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Arthritis Rheum. 2008 May 15;59(5):623-31.

Thinking about movement hurts: the effect of motor imagery on pain and swelling in people with chronic arm pain.

Source

Department of Physiology, Anatomy & Genetics, Oxford University, Oxford, UK. lorimer.moseley@medsci.ox.ac.uk

Abstract

OBJECTIVE:

Chronic painful disease is associated with pain on movement, which is presumed to be caused by noxious stimulation. We investigated whether motor imagery, in the absence of movement, increases symptoms in patients with chronic arm pain.

METHODS:

Thirty-seven subjects performed a motor imagery task. Pain and swelling were measured before, after, and 60 minutes after the task. Electromyography findings verified no muscle activity. Patients with complex regional pain syndrome (CRPS) were compared with those with non-CRPS pain. Secondary variables from clinical, psychophysical, and cognitive domains were related to change in symptoms using linear regression.

RESULTS:

Motor imagery increased pain and swelling. For CRPS patients, pain (measured on a 100-mm visual analog scale) increased by a mean +/- SD of 5.3 +/- 3.9 mm and swelling by 8% +/- 5%. For non-CRPS patients, pain increased by 1.4 +/- 4.1 mm and swelling by 3% +/- 4%. There were no differences between groups (P > 0.19 for both). Increased pain and swelling related positively to duration of symptoms and performance on a left/right judgment task that interrogated the body schema, autonomic response, catastrophic thoughts about pain, and fear of movement (r > 0.42, P < 0.03 for all).

CONCLUSION:

Motor imagery increased pain and swelling in patients with chronic painful disease of the arm. The effect increased in line with the duration of symptoms and seems to be modulated by autonomic arousal and beliefs about pain and movement. The results highlight the contribution of cortical mechanisms to pain on movement, which has implications for treatment.

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Brain. 2009 Nov;132(Pt 11):3142-51. Epub 2009 Sep 14.

Space-based, but not arm-based, shift in tactile processing in complex regional pain syndrome and its relationship to cooling of the affected limb.

Source

PaiN Group & Department of Physiology, Anatomy & Genetics, University of Oxford, UK. lorimer.moseley@gmail.com

Abstract

Complex regional pain syndrome (CRPS) occurs after stroke, but most cases develop after peripheral trauma and without evidence of brain trauma. However, CRPS is associated with symptoms that appear similar to those observed in patients suffering from hemispatial neglect. Ten participants (four males) with CRPS of one arm performed temporal order judgements of pairs of vibrotactile stimuli, one delivered to each hand, at one of 10 possible stimulus onset asynchronies, under two conditions: arms held each side of the midline and arms crossed over the midline. Participants released a foot switch to indicate which hand had been stimulated first. The order of conditions was randomized and the foot under which the switch was positioned was counterbalanced. There were two blocks of 150 trials in each condition. The stimulus onset asynchronicity at which the participants were equally likely to select either hand, the point of subjective simultaneity (PSS), was compared between conditions and between those with left or right-sided symptoms. When arms were not crossed, the participants prioritized stimuli from the unaffected limb over those from the affected limb (mean +/- SD PSS = 25 +/- 7.5 ms) and the magnitude of the PSS strongly related to the degree to which the affected hand was cooler than the unaffected hand (r = 0.942, P < 0.001). When the arms were crossed, the effect was reversed: the participants prioritized stimuli from the affected limb over those from the unaffected limb [PSS = -18 +/- 13 ms; main effect of condition F (1, 9) = 98.6, P < 0.001]. There was no effect of the side of symptoms. These results show that CRPS is associated with a deficit in tactile processing that is defined by the space in which the affected limb normally resides, not by the affected limb itself, and which relates to the relative cooling of the affected limb. This pattern is consistent with data from those with hemispatial neglect after stroke and raises the possibility that chronic CRPS involves a type of spatial neglect.

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Neurology. 2004 Jun 22;62(12):2182-6.

Why do people with complex regional pain syndrome take longer to recognize their affected hand?

Moseley GL.

Source

Department of Physiotherapy, The University of Queensland, and Royal Brisbane & Women’s Hospital, Brisbane, Australia. l.moseley@uq.edu.au

Abstract

BACKGROUND:

People with complex regional pain syndrome (CRPS) take longer to recognize the laterality of a pictured hand when it coincides with their affected hand. The author explored two aspects of this phenomenon: whether the duration of symptoms relates to the extent of the delay and whether guarding-type mechanisms are involved.

METHODS:

Eighteen patients with CRPS type 1 of the wrist and 18 matched control subjects performed a hand laterality recognition task. McGill pain questionnaire, Neuropathic Pain Scale, and response time (RT) to recognize hand laterality were analyzed. Regressions related 1) mean RT for patients to the duration of symptoms and to pain intensity; and 2) mean RT for each picture to the predicted pain on executing that movement as judged by the patient, and to the awkwardness of the movement that would be required.

RESULTS:

For patients, the duration of symptoms correlated with mean RT (Spearman rho = 0.44; p = 0.02). Predicted pain rating explained 45% of the variance in RT for each picture for each patient (p < 0.01).

CONCLUSIONS:

The results suggest that in patients with complex regional pain syndrome type 1, delayed recognition of hand laterality is related to the duration of symptoms and to the pain that would be evoked by executing the movement. The former is consistent with chronic pain and disuse and may involve reorganization of the cortical correlate of body schema. The latter is consistent with a guarding-type response that probably occurs upstream of the motor cortex at a motor planning level

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Pain. 2008 Jul 31;137(3):600-8. Epub 2007 Dec 3.

Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain.

Moseley GL, Zalucki NM, Wiech K.

Source

Pain Imaging Neuroscience Group, Department of Physiology, Anatomy & Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford OX13QX, UK. lorimer.moseley@medsci.ox.ac.uk

Abstract

Chronic pain is often associated with reduced tactile acuity. A relationship exists between pain intensity, tactile acuity and cortical reorganisation. When pain resolves, tactile function improves and cortical organisation normalises. Tactile acuity can be improved in healthy controls when tactile stimulation is associated with a behavioural objective. We hypothesised that, in patients with chronic limb pain and decreased tactile acuity, discriminating between tactile stimuli would decrease pain and increase tactile acuity, but tactile stimulation alone would not. Thirteen patients with complex regional pain syndrome (CRPS) of one limb underwent a waiting period and then approximately 2 weeks of tactile stimulation under two conditions: stimulation alone or discrimination between stimuli according to their diameter and location. There was no change in pain (100 mm VAS) or two-point discrimination (TPD) during a no-treatment waiting period, nor during the stimulation phase (p > 0.32 for both). Pain and TPD were lower after the discrimination phase [mean (95% CI) effect size for pain VAS = 27 mm (14-40 mm) and for TPD = 5.7 mm (2.9-8. ), p < 0.015 for both]. These gains were maintained at three-month follow-up. We conclude that tactile stimulation can decrease pain and increase tactile acuity when patients are required to discriminate between the type and location of tactile stimuli.

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Neurology. 2006 Dec 26;67(12):2129-34. Epub 2006 Nov 2.

Graded motor imagery for pathologic pain: a randomized controlled trial.

Moseley GL.

Source

Department of Physiology, Anatomy & Genetics & fMRIB Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. lorimer.moseley@ndm.ox.ac.uk

Abstract

BACKGROUND:

Phantom limb and complex regional pain syndrome type 1 (CRPS1) are characterized by changes in cortical processing and organization, perceptual disturbances, and poor response to conventional treatments. Graded motor imagery is effective for a small subset of patients with CRPS1.

OBJECTIVE:

To investigate whether graded motor imagery would reduce pain and disability for a more general CRPS1 population and for people with phantom limb pain.

METHODS:

Fifty-one patients with phantom limb pain or CRPS1 were randomly allocated to motor imagery, consisting of 2 weeks each of limb laterality recognition, imagined movements, and mirror movements, or to physical therapy and ongoing medical care.

RESULTS:

There was a main statistical effect of treatment group, but not diagnostic group, on pain and function. The mean (95% CI) decrease in pain between pre- and post-treatment (100 mm visual analogue scale) was 23.4 mm (16.2 to 30.4 mm) for the motor imagery group and 10.5 mm (1.9 to 19.2 mm) for the control group. Improvement in function was similar and gains were maintained at 6-month follow-up.

CONCLUSION:

Motor imagery reduced pain and disability in these patients with complex regional pain syndrome type I or phantom limb pain, but the mechanism, or mechanisms, of the effect are not clear.

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Pain. 2004 Mar;108(1-2):192-8.

Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial.

Moseley GL.

Source

Department of Physiotherapy, The University of Queensland and Royal Brisbane and Women’s Hospital, Herston, 4029 Brisbane, Qld, Australia. l.moseley@mailbox.uq.edu.au

Abstract

Complex regional pain syndrome type 1 (CRPS1) involves cortical abnormalities similar to those observed in phantom pain and after stroke. In those groups, treatment is aimed at activation of cortical networks that subserve the affected limb, for example mirror therapy. However, mirror therapy is not effective for chronic CRPS1, possibly because movement of the limb evokes intolerable pain. It was hypothesised that preceding mirror therapy with activation of cortical networks without limb movement would reduce pain and swelling in patients with chronic CRPS1. Thirteen chronic CRPS1 patients were randomly allocated to a motor imagery program (MIP) or to ongoing management. The MIP consisted of two weeks each of a hand laterality recognition task, imagined hand movements and mirror therapy. After 12 weeks, the control group was crossed-over to MIP. There was a main effect of treatment group (F(1, 11) = 57, P < 0.01) and an effect size of approximately 25 points on the Neuropathic pain scale. The number needed to treat for a 50% reduction in NPS score was approximately 2. The effect of treatment was replicated in the crossed-over control subjects. The results uphold the hypothesis that a MIP initially not involving limb movement is effective for CRPS1 and support the involvement of cortical abnormalities in the development of this disorder. Although the mechanisms of effect of the MIP are not clear, possible explanations are sequential activation of cortical pre-motor and motor networks, or sustained and focussed attention on the affected limb, or both.

Any questions, do get in touch: www.specialistpainphysio.com

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