#CRPS Bugle | 28th July

CRPS BugleImpaired Recognition of Social Emotion in Patients With Complex Regional Pain Syndrome.

J Pain. 2013 Jul 19.

Shin NY, Kang DH, Jang JH, Park SY, Hwang JY, Kim SN, Byun MS, Park HY, Kim YC.


Multiple brain areas involved in nociceptive, autonomic, and social-emotional processing are disproportionally changed in patients with complex regional pain syndrome (CRPS). Little empirical evidence is available involving social cognitive functioning in patients with chronic pain conditions. We investigated the ability of patients with CRPS to recognize the mental/emotional states of other people. Forty-three patients with CRPS and 30 healthy controls performed the Reading Mind in the Eyes Test, which consists of photos in which human eyes express various emotional and mental states. Neuropsychological tests, including the Wisconsin Card Sorting Test, the stop-signal test, and the reaction time test, were administered to evaluate other cognitive functions. Patients with CRPS were significantly less accurate at recognizing emotional states in other persons, but not on other cognitive tests, compared with control subjects. We found a significant association between the deficit in social-emotion recognition and the affective dimension of pain, whereas this deficit was not related to the sensory dimension of pain. Our findings suggest a disrupted ability to recognize others’ mental/emotional states in patients with CRPS.


This article demonstrated a deficit in inferring mental/emotional states of others in patients with CRPS that was related to pain affect. Our study suggests that additional interventions directed toward reducing distressful affective pain may be helpful to restore social cognitive processing in patients with CRPS.

RS – addressing all the dimensions of pain is vital in a comprehensive treatment & training programme: physical, emotional & cognitive. Awareness of deficits such as ‘inferring mental/emotional states of others’, as seen in this study, allows clinicians to account for certain behaviours and responses that can be seen during the assessment process and treatment sessions. Subsequently, the therapy choice can be made on an individual basis to target the deficits.


Altered Resting-State Functional Connectivity in Complex Regional Pain Syndrome.

J Pain. 2013 Jun 18.

Bolwerk A, Seifert F, Maihöfner C.


This study explored the functional connectivity between brain regions implicated in the default mode network, the sensorimotor cortex (S1/M1), and the intraparietal sulcus (IPS/MIP) at rest in patients with complex regional pain syndrome. It also investigated how possible alterations are associated with neuropathic pain. Our group used functional magnetic resonance imaging to investigate functional brain connectivity in 12 complex regional pain syndrome patients in comparison with that in 12 age- and sex-matched healthy controls. Data were analyzed using a seed voxel correlation analysis and an independent component analysis. An analysis of covariance was employed to relate alterations in functional connectivity with clinical symptoms. We found significantly greater reductions in functional default mode network connectivity in patients compared to controls. The functional connectivity maps of S1/M1 and IPS/MIP in patients revealed greater and more diffuse connectivity with other brain regions, mainly with the cingulate cortex, precuneus, thalamus, and prefrontal cortex. In contrast, controls showed greater intraregional connectivity within S1/M1 and IPS/MIP. Furthermore, there was a trend for correlation between alterations in functional connectivity and intensity of neuropathic pain. In our findings, patients with complex regional pain syndrome have substantial spatial alterations in the functional connectivity between brain regions implicated in the resting-state default mode network, S1/M1, and IPS/MIP; these alterations show a trend of correlation with neuropathic pain intensity.


This article presents spatial alterations in the functional resting-state connectivity of complex regional pain syndrome patients. Our results add further insight into the disease states of CRPS and into the functional architecture of the resting state brains of pain patients in general.

RS: Pain emerges from the body. That is where we feel it undoubtedly. It can be a difficult leap to understand that the neural correlate sits within the brain. There is no pain centre but rather a widespread group of neurons in different brain regions that when activated, create a neurotag or neurosignature that manifests as pain where the brain perceives a threat that requires protection. It is no surprise therefore, to see a further study highlight altered activity within the brain in CRPS patients compared to a control group. From a clinical perspective, it demonstrates that we have to ‘think brain’ within the reasoning behind the design of a rehabilitation programme and in appropriate cases use therapies such as graded motor imagery


A Disturbance in Sensory Processing on the Affected Side of the Body Increases Limb Pain in Complex Regional Pain Syndrome.

Clin J Pain. 2013 Jun 19.

Drummond PD, Finch PM.



The aim of this study was to determine whether a central disturbance in somatosensory processing contributes to limb pain in complex regional pain syndrome (CRPS).


In 37 patients with CRPS, the effect of cooling the ipsilateral forehead on pain in the affected limb was compared with the effect of cooling the contralateral forehead. In addition, symptoms associated with cold-evoked limb pain were explored.


Limb pain generally increased when the ipsilateral side of the forehead was cooled but did not change when the contralateral side of the forehead was cooled. Increases were greatest in patients with heightened sensitivity to cold, brushing, and pressure-pain in the ipsilateral forehead, in patients with heightened sensitivity to pressure-pain in the limbs, and in patients with chronic symptoms. In contrast, sensitivity to light touch was diminished in the CRPS-affected limb of patients whose limb pain remained unchanged or decreased during ipsilateral forehead cooling.


These preliminary findings suggest that a central disturbance in sensory processing and pain modulation, which extends beyond the affected limb to the ipsilateral forehead, contributes to symptoms in a subgroup of patients with CRPS.

RS: A number of patients who present with pain that is underpinned by a component of central sensitisation will also, being given the chance, describe pain in other body regions and body systems. Being vigilant to this possibility is fundamental to a complete assessment, the conclusions of which will guide the treatment programme.


Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6months.

Pain. 2013 Jun 27.

Lenz M, Uçeyler N, Frettlöh J, Höffken O, Krumova EK, Lissek S, Reinersmann A, Sommer C, Stude P, Waaga-Gasser AM, Tegenthoff M, Maier C.


There is evidence that inflammatory processes are involved in at least the early phase of complex regional pain syndrome (CRPS). We compared a panel of pro- and antiinflammatory cytokines in skin blister fluids and serum from patients with CRPS and patients with upper-limb pain of other origin (non-CRPS) in the early stage (< 1year) and after 6months of pain treatment. Blister fluid was collected from the affected and contralateral nonaffected side. We used a multiplex-10 bead array cytokine assay and Luminex technology to measure protein concentrations of the cytokines interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor-alpha (TNF-α) and the chemokines eotaxin, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1β (MIP-1β). We found bilaterally increased proinflammatory TNF-α and MIP-1β and decreased antiinflammatory IL-1RA protein levels in CRPS patients compared to non-CRPS patients. Neither group showed side differences. After 6 months under analgesic treatment, protein levels of all measured cytokines in CRPS patients, except for IL-6, significantly changed bilaterally to the level of non-CRPS patients. These changes were not related to treatment outcome. In serum, only IL-8, TNF-α, eotaxin, MCP-1, and MIP-1β were detectable without intergroup differences. Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS. Almost all measured cytokine levels were comparable to those of non-CRPS patients after 6 months of analgesic treatment and were not related to treatment outcome.

RS: ‘Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS’. In some patients there is an inflammatory profile that should be noted and treated as early as possible. On-going inflammation will cause a persisting bombardment of danger signals to the spinal cord and to the higher centres. The brain does want to know about inflammation and when detected it typically hurts, the purpose being that we need to know (consciously) so that we take appropriate action. Tackling inflammation early may have a beneficial effect upon this process.


Limb-specific autonomic dysfunction in complex regional pain syndrome modulated by wearing prism glasses.

Pain. 2013 Jul 22.

Lorimer Moseley G, Gallace A, Di Pietro F, Spence C, Iannetti GD.


In unilateral upper limb complex regional pain syndrome (CRPS), the temperature of the hands is modulated by where the arms are located, relative to the body midline. We hypothesized that this effect depends on the perceived location of the hands, not on their actual location, nor on their anatomical alignment. In two separate cross-sectional randomized experiments, ten (6 female) unilateral CRPS patients wore prism glasses that laterally shifted the visual field by 20°. Skin temperature was measured before and after nine-minute periods in which the position of one hand was changed. Placing the affected hand on the healthy side of the body midline increased its temperature (Δ°C =0.47 ± 0.14°C), but not if prism glasses made the hand appear to be on the body midline (Δ°C =0.07 ± 0.06°C). Similarly, when prism glasses made the affected hand appear to be on the healthy side of the body midline, even though it was not, the affected hand warmed up (Δ°C =0.28 ± 0.14°C). When prism glasses made the healthy hand appear to be on the affected side of the body midline, even though it was not, the healthy hand cooled down (Δ°C = -0.30 ± 0.15°C). Friedman’s ANOVA and Wilcoxon’s pairs tests upheld the results (p <0.01 for all). We conclude that, in CRPS, cortical mechanisms responsible for encoding the perceived location of the limbs in space modulate the temperature of the hands.

And, another paper here:

Spatially defined modulation of skin temperature and hand ownership of both hands in patients with unilateral complex regional pain syndrome.

Brain. 2012 Dec;135(Pt 12):3676-86.

Moseley GL, Gallace A, Iannetti GD.


Numerous clinical conditions, including complex regional pain syndrome, are characterized by autonomic dysfunctions (e.g. altered thermoregulation, sometimes confined to a single limb), and disrupted cortical representation of the body and the surrounding space. The presence, in patients with complex regional pain syndrome, of a disruption in spatial perception, bodily ownership and thermoregulation led us to hypothesize that impaired spatial perception might result in a spatial-dependent modulation of thermoregulation and bodily ownership over the affected limb. In five experiments involving a total of 23 patients with complex regional pain syndrome of one arm and 10 healthy control subjects, we measured skin temperature of the hand with infrared thermal imaging, before and after experimental periods of either 9 or 10 min each, during which the hand was held on one or the other side of the body midline. Tactile processing was assessed by temporal order judgements of pairs of vibrotactile stimuli, delivered one to each hand. Pain and sense of ownership over the hand were assessed by self-report scales. Across experiments, when kept on its usual side of the body midline, the affected hand was 0.5 ± 0.3°C cooler than the healthy hand (P < 0.02 for all, a common finding in cold-type complex regional pain syndrome), and tactile stimuli delivered to the healthy hand were prioritized over those delivered to the affected hand. Simply crossing both hands over the midline resulted in (i) warming of the affected hand (the affected hand became 0.4 ± 0.3°C warmer than when it was in the uncrossed position; P = 0.01); (ii) cooling of the healthy hand (by 0.3 ± 0.3°C; P = 0.02); and (iii) reversal of the prioritization of tactile processing. When only the affected hand was crossed over the midline, it became warmer (by 0.5 ± 0.3°C; P = 0.01). When only the healthy hand was crossed over the midline, it became cooler (by 0.3 ± 0.3°C; P = 0.01). The temperature change of either hand was positively related to its distance from the body midline (pooled data: r = 0.76, P < 0.001). Crossing the affected hand over the body midline had small but significant effects on both spontaneous pain (which was reduced) and the sense of ownership over the hand (which was increased) (P < 0.04 for both). We conclude that impaired spatial perception modulated temperature of the limbs, tactile processing, spontaneous pain and the sense of ownership over the hands. These results show that complex regional pain syndrome involves more complex neurological dysfunction than has previously been considered.

RS: very cool research unravelling the complex mechanisms that underpin CRPS

Come and visit our clinic site here: Specialist Pain Physio Clinics, London for treatment and training for complex and chronic pain

CRPS Bugle 21st June

For some time studies have suggested that cortical reorganisation underpins certain features of complex regional pain syndrome. Also termed the body schema, this is in essence how we ‘feel’ ourselves and is constructed by the brain. However, the actual sense emerges from the physical body, the tissues despite the fact that the neural correlate is within the brain.

Many patients who come to the clinic with CRPS describe an altered sense of the affected area – detached, ‘not mine’, change in size perception

The study by Lorimer Moseley in 2004 outlined below looked at why those with complex regional pain syndrome tend to be slower at recognising the affected hand. This is a common finding when I assess a CRPS patient, an issue in body schema that requires addressing with a therapeutic training strategy.

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.



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.


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.


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).


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.


Neurosci Lett. 2010 Dec 17;486(3):240-5. doi: 10.1016/j.neulet.2010.09.062. 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.

Reinersmann A, Haarmeyer GS, Blankenburg M, Frettlöh J, Krumova EK, Ocklenburg S, Maier C.


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.


J Int Neuropsychol Soc. 2010 Jul;16(4):603-12. doi: 10.1017/S1355617710000299. Epub 2010 Apr 12.

Mental motor imagery and chronic pain: the foot laterality task.

Coslett HB, Medina J, Kliot D, Burkey A.


Several lines of evidence suggest that mental motor imagery is subserved by the same cognitive operations and brain structures that underlie action. Additionally, motor imagery is informed by the anticipated sensory consequences of action, including pain. We reasoned that motor imagery could provide a useful measure of chronic leg or foot pain. Forty subjects with leg pain (19 bilateral, 11 right, and 10 left leg pain), 42 subjects with chronic pain not involving the legs, and 38 controls were shown 12 different line drawings of the right or left foot and asked to indicate which foot was depicted. Previous work suggests that subjects perform this task by mentally rotating their foot to match the visually presented stimulus. All groups of subjects were slower and less accurate with stimuli that required a greater degree of mental rotation of their foot. Subjects with leg pain were both slower and less accurate than normal and pain control subjects in responding to drawings of a painful extremity. Furthermore, subjects with leg pain exhibited a significantly greater decrement in performance for stimuli that required larger amplitude mental rotations. These data suggest that motor imagery may provide important insights into the nature of the pain experience.


Eur J Pain. 2010 Nov;14(10):1007-13. Full article here

Mental motor imagery indexes pain: the hand laterality task.

Coslett HB, Medina J, Kliot D, Burkey AR.


Mental motor imagery is subserved by the same cognitive systems that underlie action. In turn, action is informed by the anticipated sensory consequences of movement, including pain. In light of these considerations, one would predict that motor imagery would provide a useful measure pain-related functional interference. We report a study in which 19 patients with chronic musculoskeletal or radiculopathic arm or shoulder pain, 24 subjects with chronic pain not involving the arm/shoulder and 41 normal controls were asked to indicate if a line drawing was a right or left hand. Previous work demonstrated that this task is performed by mental rotation of the subject’s hand to match the stimulus. Relative to normal and pain control subjects, arm/shoulder pain subjects were significantly slower for stimuli that required greater amplitude rotations. For the arm/shoulder pain subjects only there was a correlation between degree of slowing and the rating of severity of pain with movement but not the non-specific pain rating. The hand laterality task may supplement the assessment of subjects with chronic arm/shoulder pain.


Brain Res. 2010 Oct 8;1355:104-11. Full article here

Contributions of efference copy to limb localization: evidence from deafferentation.

Medina J, Jax SA, Brown MJ, Coslett HB.


CRPS BuglePrevious research with deafferented subjects suggests that efference copy can be used to update limb position. However, the contributions of efference copy to limb localization are currently unclear. We examined the performance of JDY, a woman with severe, longstanding proprioceptive deficits from a sensory peripheral neuropathy, on a reaching task to explore the contribution of efference copy to trajectory control. JDY and eight healthy controls reached without visual feedback to a target that either remained stationary or jumped to a second location after movement initiation. JDY consistently made hypermetric movements to the final target, exhibiting significant problems with amplitude control. Despite this amplitude control deficit, JDY’s performance on jump trials showed that the angle of movement correction (angle between pre- and post-correction movement segments) was significantly correlated with the distance (but not time) of movement from start to turn point. These data suggest that despite an absence of proprioceptive and visual information regarding hand location, JDY derived information about movement distance that informed her movement correction on jump trials. The same type of information that permitted her to correct movement direction on-line, however, was not available for control of final arm position. We propose that efference copy can provide a consistent estimate of limb position that becomes less informative over the course of the movement. We discuss the implications of these data for current models of motor control.

Visit our main site here: Specialist Pain Physio Clinics for information about our neuroscience based treatment programmes for CRPS

Some background studies to imagery work for painful conditions | part 1

Brain. 2001 Oct;124(Pt 10):2098-104.

Pain and the body schema: evidence for peripheral effects on mental representations of movement.

Schwoebel J, Friedman R, Duda N, Coslett HB.


Some accounts of body representations postulate a real-time representation of the body in space generated by proprioceptive, somatosensory, vestibular and other sensory inputs; this representation has often been termed the ‘body schema’. To examine whether the body schema is influenced by peripheral factors such as pain, we asked patients with chronic unilateral arm pain to determine the laterality of pictured hands presented at different orientations. Previous chronometric findings suggest that performance on this task depends on the body schema, in that it appears to involve mentally rotating one’s hand from its current position until it is aligned with the stimulus hand. We found that, as in previous investigations, participants’ response times (RTs) reflected the degree of simulated movement as well as biomechanical constraints of the arm. Importantly, a significant interaction between the magnitude of mental rotation and limb was observed: RTs were longer for the painful arm than for the unaffected arm for large-amplitude imagined movements; controls exhibited symmetrical RTs. These findings suggest that the body schema is influenced by pain and that this task may provide an objective measure of pain.


Arch Neurol. 2009 May;66(5):557-60.

The mirror neuron system.


Mirror neurons are a class of neurons, originally discovered in the premotor cortex of monkeys, that discharge both when individuals perform a given motor act and when they observe others perform that same motor act. Ample evidence demonstrates the existence of a cortical network with the properties of mirror neurons (mirror system) in humans. The human mirror system is involved in understanding others’ actions and their intentions behind them, and it underlies mechanisms of observational learning. Herein, we will discuss the clinical implications of the mirror system.


Annu Rev Neurosci. 2004;27:169-92.

The mirror-neuron system.

Rizzolatti G, Craighero L.


A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others’ actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism–the mirror-neuron mechanism–that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.


Acta Psychol (Amst). 2001 Apr;107(1-3):155-81.

Integrating cognitive psychology, neurology and neuroimaging.

Parsons LM.


In the last decade, there has been a dramatic increase in research effectively integrating cognitive psychology, functional neuroimaging, and behavioral neurology. This new work is typically conducting basic research into aspects of the human mind and brain. The present review features as examples of such integrations two series of studies by the author and his colleagues. One series, employing object recognition, mental motor imagery, and mental rotation paradigms, clarifies the nature of a cognitive process, imagined spatial transformations used in shape recognition. Among other implications, it suggests that when recognizing a hand’s handedness, imagining one’s body movement depends on cerebrally lateralized sensory-motor structures and deciding upon handedness depends on exact match shape confirmation. The other series, using cutaneous, tactile, and auditory pitch discrimination paradigms, elucidates the function of a brain structure, the cerebellum. It suggests that the cerebellum has non-motor sensory support functions upon which optimally fine sensory discriminations depend. In addition, six key issues for this integrative approach are reviewed. These include arguments for the value and greater use of: rigorous quantitative meta-analyses of neuroimaging studies; stereotactic coordinate-based data, as opposed to surface landmark-based data; standardized vocabularies capturing the elementary component operations of cognitive and behavioral tasks; functional hypotheses about brain areas that are consistent with underlying microcircuitry; an awareness that not all brain areas implicated by neuroimaging or neurology are necessarily directly involved in the associated cognitive or behavioral task; and systematic approaches to integrations of this kind.


Behav Brain Res. 1996 May;77(1-2):45-52.

The neurophysiological basis of motor imagery.

Decety J.


Motor imagery may be defined as a dynamic state during which representations of a given motor act are internally rehearsed in working memory without any overt motor output. What neural processes underlie the generation of motor imagery? This paper reviews physiological evidence from measurements of regional brain activity and from measurements of autonomic responses in normal subjects and behavioral observations from brain damaged patients. It is proposed that motor imagery shares neural mechanisms with processes used in motor control. This review emphasizes the importance of the prefrontal cortex and its connections to the basal ganglia in maintaining dynamic motor representations in working memory. This view fits with the general idea that the prefrontal cortex is responsible for the creation and maintenance of explicit representations that guide thought and action.


Brain Res Cogn Brain Res. 1996 Mar;3(2):87-93.

Do imagined and executed actions share the same neural substrate?

Decety J.


This paper addresses the issue of the functional correlates of motor imagery, using mental chronometry, monitoring the autonomic responses and measuring cerebral blood flow in humans. The timing of mentally simulated actions closely mimic actual movement times. Autonomic responses during motor imagery parallel the autonomic responses to actual exercise. Cerebral blood flow increases are observed in the motor cortices involved in the programming of actual movement (i.e. premotor cortex, anterior cingulate, inferior parietal lobule and cerebellum). These three sources of data provide converging support for the hypothesis that imagined and executed actions share, to some extent, the same central structures.


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. melanie.lenz@rub.de


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. victoria@htcsllc.com


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. martin.diers@zi-mannheim.de


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. melita.giummarra@monash.edu


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.

Imagery & mirrors

Many readers will know about mirror box therapy for CRPS and other painful conditions. The Graded Motor Imagery Programme that we use at Specialist Pain Physio is sequential training that starts with laterality, progressing to imagined movements and then to mirror therapy. There is some really good data for the programme and CRPS but it can also be effective with other chronic pains. Interestingly we are now seeing components of GMI being used and written about in the popular press, most recently for Parkinson’s disease and arthritis.

Brain training for pain

A brief article in New Scientist describes the Parkinson’s research by David Linden at Cardiff University. 10 subjects were asked to think about movement for 45 minutes whilst they were having brain scans. Five of the subjects were given feedback that showed them how they were activating the brain and all were asked to practice the imagery at home. Two months later rigidity and tremor had reduced some 37% in the feedback group. The thinking is that there is cortical change underpinning this improved function that is feasible.

Mirror therapy for pain

At The Society for Neuroscience annual meeting 2011 a small study was performed with arthritis (OA & RA) patients used mirror therapy. Subjects observed the moving reflection of the researcher’s hand in the mirror whilst producing the same movement themselves with their hidden hand. After 1 minute it was noted that the subjects pain improved. This was reported in The Guardian today.

For details on our treatment programmes including imagery, mirror therapy, graded motor imagery and other neuroscience-based techniques, come and see our website at http://www.specialistpainphysio.com or call 07518 445491. Our clinics are based in London and Surrey http://www.specialistpainphysio.com/clinics