CRPS March literature review

Neurology. 2011 Sep 13;77(11):1096-101. Epub 2011 Aug 31.

Bilateral somatosensory cortex disinhibition in complex regional pain syndrome type I.

Department of Neurology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Ruhr-University Bochum, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.


In a previous study, we found bilateral disinhibition in the motor cortex of patients with complex regional pain syndrome (CRPS). This finding suggests a complex dysfunction of central motor-sensory circuits. The aim of our present study was to assess possible bilateral excitability changes in the somatosensory system of patients with CRPS.

We measured paired-pulse suppression of somatosensory evoked potentials in 21 patients with unilateral CRPS I involving the hand. Eleven patients with upper limb pain of non-neuropathic origin and 21 healthy subjects served as controls. Innocuous paired-pulse stimulation of the median nerve was either performed at the affected and the unaffected hand, or at the dominant hand of healthy controls, respectively.

We found a significant reduction of paired-pulse suppression in both sides of patients with CRPS, compared with control patients and healthy control subjects.

These findings resemble our findings in the motor system and strongly support the hypothesis of a bilateral complex impairment of central motor-sensory circuits in CRPS I.


Anesthesiology. 2012 Feb 15. [Epub ahead of print]

Substance P Signaling Controls Mast Cell Activation, Degranulation, and Nociceptive Sensitization in a Rat Fracture Model of Complex Regional Pain Syndrome.


Patients with complex regional pain syndrome have increased tryptase in the skin of the affected extremity indicating mast cell (MC) accumulation and degranulation, processes known to be mediated by substance P (SP). The dysregulation of SP release from primary afferent neurons is characteristic of complex regional pain syndrome. The authors hypothesized that SP acting through the neurokinin-1 receptor results in mast cell accumulation, degranulation, and nociceptive sensitization in a rat model of complex regional pain syndrome.

Groups of 6-10 rats underwent tibia fracture and hind limb casting for 4 weeks, and the hind paw skin was harvested for histologic and immunohistochemical analysis. The effects of a selective neurokinin-1 receptor antagonist (LY303870) and of direct SP intraplantar injection were measured. Dermal MC degranulation induced by sciatic nerve stimulation and the effects of LY303870 on this process were investigated. Finally, the antinociceptive effects of acute and chronic treatment with a MC degranulator (48/80) were tested.

The authors observed that fracture caused MC accumulation, activation, and degranulation, which were inhibited by LY303870; the percentage of MCs in close proximity to peptidergic nerve fibers increased after fracture; electrical stimulation caused MC activation and degranulation, which was blocked by LY303870; intraplantar SP-induced MC degranulation and acute administration of 48/80 caused MC degranulation and enhanced postfracture nociception, but MC-depleted animals showed less sensitization.

These results indicate that facilitated peptidergic neuron-MC signaling after fracture can cause MC accumulation, activation, and degranulation in the injured limb, resulting in nociceptive sensitization.


Pain. 2012 Feb 13. [Epub ahead of print]

Motor control in complex regional pain syndrome: A kinematic analysis.

Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.


This study evaluated movement velocity, frequency, and amplitude, as well as the number of arrests in three different subject groups, by kinematic analysis of repetitive movements during a finger tapping (FT) task. The most affected hands of 80 patients with complex regional pain syndrome (CRPS) were compared with the most affected hands of 60 patients with Parkinson disease (PD) as well as the nondominant hands of 75 healthy control (HC) subjects. Fifteen seconds of FT with thumb and index finger were recorded by a 60-Hz camera, which allowed the whole movement cycle to be evaluated and the above mentioned movement parameters to be calculated. We found that CRPS patients were slower and tapped with more arrests than the two other groups. Moreover, in comparison with the hands of the HC subjects, the unaffected hands of the CRPS patients were also impaired in these domains. Impairment was not related to pain. Dystonic CRPS patients performed less well than CRPS patients without dystonia. In conclusion, this study shows that voluntary motor control in CRPS patients is impaired at both the affected as well as the unaffected side, pointing at involvement of central motor processing circuits.


Neuromodulation. 2012 Feb 13. doi: 10.1111/j.1525-1403.2011.00424.x. [Epub ahead of print]

Spinal Cord Stimulation in Complex Regional Pain Syndrome Type I of Less Than 12-Month Duration.

Department of Anesthesiology and Pain Therapy, St Elisabeth Hospital, Tilburg, The Netherlands; Department of Anesthesiology and Pain Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands; Department of Anesthesiology and Multidisciplinary Pain Centre, Hospital Oost-Limburg, Genk, Belgium; Department of Neurology, Maastricht University Medical Centre, Maastricht, The Netherlands; and Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands.


Introduction:  Complex regional pain syndrome type 1 (CRPS-1) has a 31% probability of becoming chronic. The early use of spinal cord stimulation (SCS) has been recommended as a strategy to prevent chronicity and functional impairment. Methods:  In a prospective study, we treated 74 CRPS-1 patients with a mean disease duration of 17 weeks with standard therapy consisting of physical therapy, topical dimethyl sulfoxide, analgesics, transcutaneous stimulation, and sympathetic blockade. Patients who did not respond to standard therapy were offered a treatment with SCS. In these patients, we investigated the impact on pain, quality of life, and function. Results:  Out of these 74 patients treated with standard therapy, six patients were included for early SCS treatment. The overall mean pain relief after one year was 35%. The mental component of the Short Form 36 improved; however, there was no effect on the physical component. None of the SCS treated patients showed a clear improvement in functional outcome. Discussion:  We conclude that the feasibility of performing a randomized controlled trial on early SCS therapy in CRPS-1 is low because of the good disease improvement with standard therapy in the first year after onset. This study raises questions about the need to use SCS early in the course of CRPS-1 because of the probable lack of additional benefit compared with SCS in chronic CRPS-1.


Eur J Pain. 2012 Feb;16(2):182-95. doi: 10.1016/j.ejpain.2011.06.016.

Enhanced pain and autonomic responses to ambiguous visual stimuli in chronic Complex Regional Pain Syndrome (CRPS) type I.

Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath, BA1 1RL, UK; University of Bath, Bath, BA2 7AY, UK; Royal National Orthopaedic Hospital, Brockley Hill, Stanmore, HA7 4LP, UK.


Cortical reorganisation of sensory, motor and autonomic systems can lead to dysfunctional central integrative control. This may contribute to signs and symptoms of Complex Regional Pain Syndrome (CRPS), including pain. It has been hypothesised that central neuroplastic changes may cause afferent sensory feedback conflicts and produce pain. We investigated autonomic responses produced by ambiguous visual stimuli (AVS) in CRPS, and their relationship to pain. Thirty CRPS patients with upper limb involvement and 30 age and sex matched healthy controls had sympathetic autonomic function assessed using laser Doppler flowmetry of the finger pulp at baseline and while viewing a control figure or AVS. Compared to controls, there were diminished vasoconstrictor responses and a significant difference in the ratio of response between affected and unaffected limbs (symmetry ratio) to a deep breath and viewing AVS. While viewing visual stimuli, 33.5% of patients had asymmetric vasomotor responses and all healthy controls had a homologous symmetric pattern of response. Nineteen (61%) CRPS patients had enhanced pain within seconds of viewing the AVS. All the asymmetric vasomotor responses were in this group, and were not predictable from baseline autonomic function. Ten patients had accompanying dystonic reactions in their affected limb: 50% were in the asymmetric sub-group. In conclusion, there is a group of CRPS patients that demonstrate abnormal pain networks interacting with central somatomotor and autonomic integrational pathways.


J Hand Ther. 2011 Apr-Jun;24(2):164-8; quiz 169. Epub 2011 Feb 9.

Graded motor imagery.

Hand Therapy Consultation Services, Richmond, Vermont 05477, USA.


New information regarding cortical changes in patients with chronic pain has prompted a reevaluation of the typical “bottom up” treatment for pain, which focuses on peripheral nociceptive stimuli. More recently, increasing considerations for chronic pain are focused from the “top down” cortical central processing perspective. Graded motor imagery (GMI) is one treatment technique from the “top down” paradigm designed to treat chronic pain. This technique attempts to sequentially normalize central processing to remediate chronic pain. This article briefly summarizes the basic components of GMI, targeting complex regional pain in the upper limb, and describes a case where this method was successfully integrated. The initial research and clinical experience is promising and indicates that patients with chronic pain may benefit from using GMI to “retrain the brain.”


Pain. 2010 May;149(2):296-304. Epub 2010 Mar 31.

Mirrored, imagined and executed movements differentially activate sensorimotor cortex in amputees with and without phantom limb pain.

Department of Clinical and Cognitive Neuroscience, Central Institute of Mental Health, University of Heidelberg, D-68159 Mannheim, Germany.


Extended viewing of movements of the intact hand in a mirror as well as motor imagery has been shown to decrease pain in phantom pain patients. We used functional magnetic resonance imaging to assess the neural correlates of mirrored, imagined and executed hand movements in 14 upper extremity amputees – 7 with phantom limb pain (PLP) and 7 without phantom limb pain (non-PLP) and 9 healthy controls (HC). Executed movement activated the contralateral sensorimotor area in all three groups but ipsilateral cortex was only activated in the non-PLP and HC group. Mirrored movements activated the sensorimotor cortex contralateral to the hand seen in the mirror in the non-PLP and the HC but not in the PLP. Imagined movement activated the supplementary motor area in all groups and the contralateral primary sensorimotor cortex in the non-PLP and HC but not in the PLP. Mirror- and movement-related activation in the bilateral sensorimotor cortex in the mirror movement condition and activation in the sensorimotor cortex ipsilateral to the moved hand in the executed movement condition were significantly negatively correlated with the magnitude of phantom limb pain in the amputee group. Further research must identify the causal mechanisms related to mirror treatment, imagined movements or movements of the other hand and associated changes in pain perception.


Curr Opin Anaesthesiol. 2011 Oct;24(5):524-31.

Phantom limb pain and bodily awareness: current concepts and future directions.

Experimental Neuropsychology Research Unit, Monash University, Clayton, Victoria, Australia.


Phantom pain is a frequent consequence of amputation or deafferentation. There are many possible contributing mechanisms, including stump-related pathology, spinal and cortical changes. Phantom limb pain is notoriously difficult to treat. Continued consideration of the factors associated with phantom pain and its treatment is of utmost importance, not only to advance the scientific knowledge about the experience of the body and neuropathic pain, but also fundamentally to promote efficacious pain management.

This review first discusses the mechanisms associated with phantom pain and summarizes the current treatments. The mechanisms underlying phantom pain primarily relate to peripheral/spinal dysfunction, and supraspinal and central plasticity in sensorimotor body representations. The most promising methods for managing phantom pain address the maladaptive changes at multiple levels of the neuraxis, for example, complementing pharmacological administration with physical, psychological or behavioural intervention. These supplementary techniques are even efficacious in isolation, perhaps by replacing the absent afferent signals from the amputated limb, thereby restoring disrupted bodily representations.

Ultimately, for optimal patient outcomes, treatments should be both symptom and mechanism targeted.


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