Unilateral Complex Regional Pain Syndrome Research Articles

Virtual Reality-Induced Sensorimotor Conflict Evokes Limb-Specific Sensory Disturbances in Complex Regional Pain Syndrome

The origin of sensory disturbances in complex regional pain syndrome (CRPS) remains unclear. It has been hypothesized that such disturbances are due to attentional effects and/or sensorimotor integration deficits. If sensory disturbances are explained by sensorimotor integration deficits, they would be expected to be specific in terms of the category of sensation evoked and in terms of localization. Objective 1: To test whether sensory disturbances evoked by a unilateral sensorimotor conflict are specific to the painful limb and differ according to the category of sensory disturbances in individuals with a unilateral CRPS compared to healthy controls (HC). Objective 2: To assess the association between clinical characteristics and conflict-induced sensory disturbances. Objective 3: To assess conflict-induced motor disturbances. Ten adults with upper limb (UL) CRPS and 23 HC were recruited. Sensorimotor conflict was elicited with a KINARM exoskeleton interfaced with a 2D virtual environment allowing the projection of a virtual UL that was moving in either a congruent or incongruent manner relative to the actual UL movement. Participants rated sensory disturbances from 0 (no change) to 3 (high change) on a 8-item questionnaire. Items were classified into two Categories (Category 1: pain, discomfort, the feeling of losing a limb, change in weight and temperature; Category 2: feelings of peculiarity, the impression of gaining a limb and losing control). Motor disturbances were quantified as mediolateral drift and changes in amplitude of UL movement. Clinical characteristics included the intensity and duration of pain, proprioception, and body perception. CRPS participants report higher Category 1 than Category 2 disturbances for the Affected limb (while the reverse was observed for HC and for the Unaffected limb). In addition, no difference was observed between the Unaffected limb in CRPS and the Dominant limb in HC for Category 2 disturbances, while higher conflict sensitivity was observed for Category 1 disturbances. Conflict sensitivity was only related to higher pain for Category 1 disturbances in the Affected limb. Finally, no effect on motor disturbances was observed. While they do not completely rule out the attentional hypothesis, these results support the hypothesis of sensorimotor integration deficits.

Characterising sensorimotor adaptation in Complex Regional Pain Syndrome

It has been suggested that sensorimotor conflict contributes to the maintenance of some pathological pain conditions, implying that there are problems with the adaptation processes that normally resolve such conflict. We tested whether sensorimotor adaptation is impaired in people with Complex Regional Pain Syndrome (CRPS) by characterising their adaption to lateral prismatic shifts in vision. People with unilateral upper-limb CRPS Type I (n = 17), and pain-free individuals (n = 18; matched for age, sex, and handedness) completed prism adaptation with their affected/non-dominant and non-affected/dominant arms. We examined 1) the rate at which participants compensated for the optical shift during prism exposure (i.e., strategic recalibration), 2) endpoint errors made directly after prism adaptation (sensorimotor realignment) and the retention of these errors, and 3) kinematic markers associated with strategic control. Direct comparisons between people with CRPS and controls revealed no evidence of any differences in strategic recalibration, including no evidence for differences in a kinematic marker associated with trial-by-trial changes in movement plans during prism exposure. All participants made significant endpoint errors after prism adaptation exposure, indicative of sensorimotor realignment. Overall, the magnitude of this realignment did not differ between people with CRPS and pain-free controls. However, when endpoint errors were considered separately for each hand, people with CRPS made greater errors (indicating more rather than less realignment) when using their affected hand than their non-affected hand. No such difference was seen in controls. Taken together, these findings provide no evidence of impaired strategic control or sensorimotor realignment in people with CRPS. In contrast, they provide some indication that there could be a greater propensity for sensorimotor realignment in the CRPS-affected arm, consistent with more flexible representations of the body and peripersonal space. Our study challenges an implicit assumption of the theory that sensorimotor conflict might underlie some pathological pain conditions.

IV Ketamine-Induced Skin Temperature Changes in a Patient with Unilateral Complex Regional Pain Syndrome (CRPS) Type II

Background: Ketamine is increasingly being utilized off-label for numerous difficult-to-treat conditions when conservative treatment options fail to provide an adequate clinical response. One such condition is complex regional pain syndrome (CRPS). CRPS is characterized by pain, inflammation, vascular abnormalities, and functional decline. While ketamine has been used successfully to treat the disease, its mechanism of action remains hotly debated and not well-understood. Case Report: Here, we describe a clinical case of CRPS in a female patient who was refractory to conventional treatment options. Skin temperatures were measured in the affected and unaffected limb before, during, and after intravenous infusion with ketamine. We report that skin temperature increased in the CRPS-affected limb despite the known sympathomimetic effects of ketamine expected to produce vasoconstriction. Conclusion: The novel findings presented herein are intended to spur formal well-controlled and powered clinical studies, which may better elucidate the vascular effects of ketamine in this underserved patient population. Key words: Complex regional pain syndrome, depression, esketamine, ketamine hydrochloride, suicidality, thermal imaging

Disputing space-based biases in unilateral complex regional pain syndrome

There is some evidence that people with Complex Regional Pain Syndrome (CRPS) show reduced attention to the affected relative to unaffected limb and its surrounding space, resembling hemispatial neglect after brain injury. These neuropsychological symptoms could be related to central mechanisms of pathological pain and contribute to its clinical manifestation. However, the existing evidence of changes in spatial cognition is limited and often inconsistent. We examined visuospatial attention, the mental representation of space, and spatially-defined motor function in 54 people with unilateral upper-limb CRPS and 22 pain-free controls. Contrary to our hypotheses and previous evidence, individuals with CRPS did not show any systematic spatial biases in visuospatial attention to or representation of the side of space corresponding to their affected limb (relative to the unaffected side). We found very little evidence of directional slowing of movements towards the affected relative to unaffected side that would be consistent with motor neglect. People with CRPS were, however, slower than controls to initiate and execute movements with both their affected and unaffected hands, which suggests disrupted central motor networks. Finally, we found no evidence of any clinical relevance of changes in spatial cognition because there were no relationships between the magnitude of spatial biases and the severity of pain or other CRPS symptoms. The results did reveal potential relationships between CRPS pain and symptom severity, subjective body perception disturbance, and extent of motor impairment, which would support treatments focused on normalizing body representation and improving motor function. Our findings suggest that previously reported spatial biases in CRPS might have been overstated.

Altered updating of bodily and spatial representations after tool-use in complex regional pain syndrome

Distorted representations of the body and peripersonal space are common in complex regional pain syndrome (CRPS), and might modulate its symptoms (eg, asymmetric limb temperature). In pain-free people, such representations are malleable, and update when we interact with objects in our environment (eg, during tool-use). Distortions are also common after immobilisation, but quickly normalise once movement is regained. We tested the hypothesis that people with CRPS have problems updating bodily and spatial representations, which contributes to the maintenance of their distorted representations by preventing normalization. We also explored spatially defined modulations of hand temperature asymmetries, and any influence of updating bodily and spatial representations on this effect. Thirty-six people with unilateral CRPS (18 upper limb and 18 lower limb) and 36 pain-free controls completed tool-use tasks considered to alter body and peripersonal space representations (measured using tactile distance judgements and a visuotactile crossmodal congruency task, respectively). We also tested how the arrangement (crossed and uncrossed) of the hands and tools affected hand temperature. In upper-limb CRPS, the nonaffected arm representation updated normally, but the affected arm representation updated in the opposite to normal direction. A similar pattern was seen in lower-limb CRPS, although not significant. Furthermore, people with CRPS showed more pronounced updating of peripersonal space than the controls. We did not observe any modulation of hand temperature asymmetries by the arrangement of hands or tools. Our findings show enhanced malleability of bodily and spatial representations in CRPS, which may suggest that central mechanisms are altered in this condition.

Fine-Grained Mapping of Cortical Somatotopies in Chronic Complex Regional Pain Syndrome.

It has long been thought that severe chronic pain conditions, such as complex regional pain syndrome (CRPS), are not only associated with, but even maintained by a reorganization of the somatotopic representation of the affected limb in primary somatosensory cortex (S1). This notion has driven treatments that aim to restore S1 representations in CRPS patients, such as sensory discrimination training and mirror therapy. However, this notion is based on both indirect and incomplete evidence obtained with imaging methods with low spatial resolution. Here, we used fMRI to characterize the S1 representation of the affected and unaffected hand in humans (of either sex) with unilateral CRPS. The cortical area, location, and geometry of the S1 representation of the CRPS hand were largely comparable with those of both the unaffected hand and healthy controls. We found no differential relation between affected versus unaffected hand map measures and clinical measures (pain severity, upper limb disability, disease duration). Thus, if any map reorganization occurs, it does not appear to be directly related to pain and disease severity. These findings compel us to reconsider the cortical mechanisms underlying CRPS and the rationale for interventions that aim to “restore” somatotopic representations to treat pain.SIGNIFICANCE STATEMENT This study shows that the spatial map of the fingers in somatosensory cortex is largely preserved in chronic complex regional pain syndrome (CRPS). These findings challenge the treatment rationale for restoring somatotopic representations in complex regional pain syndrome patients.

Bone microstructure is significantly altered in CRPS-affected distal tibiae as detected by HR-pQCT: a retrospective cross-sectional study.

In the course of complex regional pain syndrome (CRPS), local osteopenia in the subchondral/subcortical areas of the affected limb represents a central manifestation. Mechanistic aspects of CRPS-associated pathologies remain unclear, and knowledge about bone morphology in CRPS-affected areas is rare. The aim of this study was to assess trabecular and cortical bone microstructure in patients with CRPS of the distal tibiae. We retrospectively analysed 14 women diagnosed with unilateral CRPS type I of the lower limb whose affected and unaffected distal tibiae were examined by high-resolution peripheral quantitative computed tomography (HR-pQCT). Laboratory tests included serum levels of calcium, phosphate, 25-hydroxyvitamin D, bone alkaline phosphatase, parathyroid hormone, osteocalcin and urinary levels of deoxypyridinoline (DPD). Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and both proximal femurs. Average urinary DPD levels, a biochemical marker of bone resorption, were elevated in the examined patient cohort (7.1 ± 1.9nmol/mmol, reference 3.0-7.0nmol/mmol). According to HR-pQCT, CRPS-affected distal tibiae showed significantly lower values of cortical BMD and cortical thickness compared to the unaffected contralateral side. Also, bone volume relative to total volume was significantly lower. Trabecular number and trabecular thickness tended to be lower in the affected tibiae. CRPS is associated with significant alterations in bone microstructure of the affected tibiae. Increased bone resorption seems to play a crucial role within a multifactorial process of CRPS-mediated bone atrophy. HR-pQCT could possibly serve as a diagnostic tool in specific CRPS therapy.

A Novel Finger Illusion Reveals Reduced Weighting of Bimanual Hand Cortical Representations in People With Complex Regional Pain Syndrome

Complex regional pain syndrome (CRPS) is associated with deficits in sensorimotor control. Herein we have used a novel finger illusion to investigate whether CRPS is associated with reduced weighting of bimanual hand representations. The illusion normally induces a compelling feeling that the hands are close together when in fact they are 12 cm apart. People with CRPS and age, gender, and dominant hand-matched controls tested the illusion in the midline then on either side of the midline. The illusion had 2 variants; the passive pincer-grip position, without contact (no grasp condition) and with contact (grasp condition) of the artificial finger. The primary outcome was the perceived vertical distance between the index fingers. Twenty people with CRPS and 20 controls participated (mean age 44.4 ± 11.7 years). During the no grasp condition, participants with CRPS perceived the vertical distance significantly closer to the actual 12 cm (mean 8.0 cm, 95% confidence interval 6.5-9.5 cm), than controls did (mean 6.4 cm, 95% confidence interval 5.5-7.2 cm]). That is, the illusion was weaker in people with CRPS than in controls during no grasp. There was no such difference during grasp; that is, both groups showed the predicted illusion response. There was no effect of hand placement relative to midline or relative to the opposite hand. We conclude that people with unilateral CRPS have lower weighting of bimanual hand representation than controls have, independent of hand location. However, adding additional cutaneous input returns those with CRPS to the expected performance. We suggest the results have clear clinical and research implications. PerspectiveAn abnormal weighting of bilateral hand representation may reflect a vulnerability for chronic CRPS, an adaptation to the disease, and/or a potential therapeutic target. That addition of cutaneous input immediately normalizes the problem points to the possible role of bimanual tasks in prevention or rehabilitation.

Spatially-defined motor deficits in people with unilateral complex regional pain syndrome

ObjectiveSpatially-defined disruption of autonomic and sensory function has been identified in Complex Regional Pain Syndrome (CRPS). This study aimed to determine whether motor performance is also disrupted in a spatially-defined manner in people with CRPS. MethodsThirteen people with CRPS type 1 of the upper limb participated in two motor experiments. In Experiment 1 participants performed a circle drawing task that primarily tested motor accuracy. In Experiment 2 participants performed a button pressing task that tested motor co-ordination. In both experiments the motor tasks were performed with either hand (affected or healthy), and on either side of the body midline – that is, on the affected side of space or healthy side of space. ResultsThere was a main effect of both Limb and Side for the motor tasks. In Experiment 1, motor accuracy for the circle drawing task was poorer when participants used their affected hand than when they used their healthy one (p < .001), and when the task was performed on the affected side of their body midline than when it was performed on the healthy side (p < .001). In Experiment 2, motor co-ordination for the button pressing task was poorer when participants used their affected hand than when they used their healthy one (p < .001), and when the task was performed on the affected side of the midline (p < .001), as compared to the healthy side of the midline. ConclusionsUnilateral CRPS is associated with a spatially-defined disruption of motor performance. Participants perform worse when the task is performed on the affected side of the body midline, regardless of whether they use their affected or healthy hand.

Inhibition of the primary sensorimotor cortex by topical anesthesia of the forearm in patients with complex regional pain syndrome.

Complex regional pain syndrome (CRPS) type I is characterized by somatosensory and motor deficits, and abnormalities have been reported for primary somatosensory (S1) and motor cortex (M1) excitability. For the latter, reduced short-latency intracortical inhibition (SICI) has been demonstrated in the somatotopic representation of the affected side. Recently, an intervention of applying anesthetic cream to the forearm has been shown to modulate both somatosensory deficits (eg, spatial tactile resolution [STR]) and SICI measured in hand muscles. We examined the efficacy of this intervention in patients with CRPS I. Cutaneous anesthesia of the forearm of the affected side was used to increase SICI of hand muscles and decrease impaired STR of the affected limb. In a double-blinded placebo-controlled study, we enrolled 12 patients with unilateral CRPS I of the hand in the chronic state. Before and after intervention, we measured motor evoked potentials of the first dorsal interosseus to obtain SICI and STR of both hand sides. Patients showed decreased STR on the tip of the thumb of their affected side, which improved after anesthetic cream but not after placebo application. Hand motor function of the affected side improved after anesthetic cream but not after placebo. Pain intensity was not modulated after intervention. At both hemispheres, SICI was decreased compared with reference values but selectively increased at the intervention side only after analgesic cream and not after placebo. Temporary deafferentation of an area neighbouring the CRPS-affected region can modulate neuropathological characteristics of CRPS and might be a promising strategy for therapeutic interventions.

(493) The influence of fear level on structural brain changes in Pediatric Complex Regional Pain Syndrome

Fear exerts a unique influence on pain-related outcomes, particularly among patients with complex regional pain syndrome (CRPS). The current study examined structural brain changes via cortical thickness and gray matter volume in pediatrics with CRPS by level of pain-related fear and in comparison to healthy matched controls. Twenty-three patients (16 females, ages 8-20) presented to a multidisciplinary pain clinic for treatment of unilateral CRPS and were matched to 18 healthy controls. All participants underwent MRI using a high-resolution T1-weighted sequence.

Patients with complex regional pain syndrome overestimate applied force in observed hand actions.

Movement accuracy is ensured by interaction between motor, somatosensory, and visual systems. In complex regional pain syndrome (CRPS), this interaction is disturbed. To explore CRPS patients' visual perception of actions, we investigated how these patients evaluate the applied force in observed hand actions of another person. Nineteen patients suffering from unilateral upper-limb CRPS and 19 healthy control subjects viewed six different videos of left- and right-hand actions. They were asked to evaluate the applied force in each hand action, as well as their subjective sensations of unpleasantness and pain during the observation. The patients overestimated the force applied in the videos: the ratings were two times as large as in the control subjects for actions performed with the hand corresponding to the patients' affected hand, and 1.5 times as large for actions corresponding to their healthy hand. The control subjects considered the stimuli neutral and painless, whereas the patients rated them unpleasant. Moreover, the patients felt increased pain during viewing actions performed with the hand corresponding to their affected side. The overestimation of force was related to the elicited unpleasantness and pain, but not to the patients' muscle strength. We propose that the overestimation of force is explained both by the pain elicited by the observation and by the abnormal sensorimotor integration that is associated with perception of increased effort. This visually elicited unpleasantness and painfulness may promote avoidance of viewing own actions, further impairing the patients' motor performance.

Intended and unintended (sensory-)motor coupling between the affected and unaffected upper limb in complex regional pain syndrome.

Motor dysfunction in complex regional pain syndrome (CRPS) has been associated with bilateral malfunction of sensory and motor circuits, which hints at abnormal coupling between the affected and the contralateral unaffected limb. In addition, clinical observations suggest that motor performance may depend on the (voluntary or automatic) context in which movements are executed. The present study aimed to examine the role of voluntary and automatic aspects of interlimb coupling in CRPS. Twenty patients with unilateral chronic CRPS and 40 healthy controls performed a set of unimanual and bimanual motor tasks that differed in the degree to which intended bilateral planning, intended afference-based error correction and unintended reflex-like entrainment were involved. Stability of interlimb coordination was reduced in CRPS patients compared to controls, especially for tasks involving active control of the affected side. In CRPS patients, intended coupling between the hands (planning, error correction) was markedly impaired, whereas unintended coupling between the hands (entrainment) appeared normal. Impaired motor control of the affected limb interfered with bimanual coordination, in particular for tasks involving voluntary (intended) as opposed to automatic (unintended) interlimb coupling. Our findings suggest inappropriate functioning of higher order centres involved in motor control of the affected limb, probably due to pain-related processes and impaired processing of proprioceptive information. Motor function of the affected limb may benefit from intended synchronization with movements of the unaffected contralateral limb, suggesting that bilateral training may be useful in patients with unilateral CRPS.

Lenalidomide for Complex Regional Pain Syndrome Type 1: Lack of Efficacy in a Phase II Randomized Study

Complex regional pain syndrome (CRPS) is a potentially debilitating chronic pain syndrome with a poorly understood but likely neuroimmune/multifactorial pathophysiology associated with axonal injury. Based on the potential contribution of proinflammatory cytokines to CRPS pathogenesis and prior research with thalidomide, we investigated lenalidomide, a thalidomide derivative, for CRPS treatment. We conducted a phase II, randomized, double-blind, placebo-controlled study to evaluate the efficacy of oral lenalidomide 10 mg once daily in consenting patients with unilateral or bilateral CRPS type 1. The study comprised 12 weeks of treatment followed by a long-term extension. The primary efficacy outcome was reduced pain in the index limb, defined as ≥30% improvement from baseline using an 11-point numeric rating scale. One hundred eighty-four subjects enrolled. The primary endpoint was not met because equal proportions of treated (16.1%) and control (16.1%) subjects achieved the outcome; however, lenalidomide was well tolerated, with no evidence of neuropathy or major adverse effects. This study is the largest controlled, blinded clinical trial in subjects with chronic CRPS using the Budapest research criteria. It demonstrates the feasibility of conducting high-quality clinical trials in CRPS type 1 and provides considerations for designing future trials. PerspectiveThis article reports an adequately powered, controlled clinical trial in subjects with CRPS. Treatment and placebo were equally effective, but the study demonstrated that lenalidomide treatment is feasible in this population. The study provides examples to consider in designing future CRPS trials.

Effects of Low-Level Laser Therapy and Interferential Current Therapy in the Treatment of Complex Regional Pain Syndrome

Objective: The aim of this study is to estimate and compare the effects of low-level laser therapy and interferential current therapy in patients with complex regional pain syndrome type I. Material and Methods: Prospective randomized clinical research, including 45 patients with post-traumatic unilateral complex regional pain syndrome type I, treated at the Clinical Center Nis from December 2004 to January 2007. Low-level laser therapy and kinesitherapy were applied in group A (n=20), whereas group B (n=25) was treated with interferential current and kinesitherapy. For assessment of the therapeutic effect, the following parameters were tested: pain intensity was determined by visual analog scale, figure-of-eight measurement was used to determine the circumference of the affected part of the extremity, and range of motion of the affected joint was measured by a standard goniometer. Results: Statistically significant differences were obtained for all tested parameters in both groups, but the difference was greater in group A compared to group B (p<0.05). Conclusion: The results of this study show that both physical procedures are effective in the treatment of complex regional pain syndrome type I, but the efficiency of laser therapy is statistically significantly higher compared to interferential current therapy.

Bilateral Hypersensitivity to Capsaicin, Thermal, and Mechanical Stimuli in Unilateral Complex Regional Pain Syndrome

Complex regional pain syndrome is multifactorial. Exaggerated inflammatory responses to limb injury may be involved. The authors hypothesized that capsaicin-induced pain and neurogenic inflammation (skin perfusion and flare area) are increased in patients with complex regional pain syndrome compared with that in controls. Twenty patients with unilateral upper-limb complex regional pain syndrome and 20 age-, sex-, and body mass index-matched controls participated. Topical capsaicin 5% was applied to the back of both hands for 30 min, and pain intensity was assessed on a visual analogue scale. A laser Doppler perfusion imager scanner estimated capsaicin-induced skin perfusion and flare area. Autonomic and small-fiber function was assessed by sensory testing, quantitative sudomotor axon reflex test, and vasoconstrictor responses. The authors found bilateral hypersensitivity to capsaicin (P ≤ 0.02), skin fold (P = 0.001), joint pressure (P < 0.0001), cold (P ≤ 0.01), and heat pain (P ≤ 0.04) in patients compared with that in controls and thermal and mechanical hyperalgesia in the complex regional pain syndrome-affected hand compared with that in the unaffected hand (P ≤ 0.001). The patients had normal capsaicin-induced flare areas, thermal detection thresholds, quantitative sudomotor axon reflex test, and vasoconstrictor responses. The main finding is bilaterally increased capsaicin-induced pain in patients compared with controls. The flare response to capsaicin was normal, suggesting that the increased pain response was not due to increased neurogenic inflammation. The bilateral hypersensitivity to painful chemical, thermal, and mechanical stimuli not confined to the innervation area of a peripheral nerve or root cannot be explained by a regional change and may partly be due to central sensitization.

Habenula functional resting-state connectivity in pediatric CRPS

The habenula (Hb) is a small brain structure located in the posterior end of the medial dorsal thalamus and through medial (MHb) and lateral (LHb) Hb connections, it acts as a conduit of information between forebrain and brainstem structures. The role of the Hb in pain processing is well documented in animals and recently also in acute experimental pain in humans. However, its function remains unknown in chronic pain disorders. Here, we investigated Hb resting-state functional connectivity (rsFC) in patients with complex regional pain syndrome (CRPS) compared with healthy controls. Twelve pediatric patients with unilateral lower-extremity CRPS (9 females; 10-17 yr) and 12 age- and sex-matched healthy controls provided informed consent to participate in the study. In healthy controls, Hb functional connections largely overlapped with previously described anatomical connections in cortical, subcortical, and brainstem structures. Compared with controls, patients exhibited an overall Hb rsFC reduction with the rest of the brain and, specifically, with the anterior midcingulate cortex, dorsolateral prefrontal cortex, supplementary motor cortex, primary motor cortex, and premotor cortex. Our results suggest that Hb rsFC parallels anatomical Hb connections in the healthy state and that overall Hb rsFC is reduced in patients, particularly connections with forebrain areas. Patients' decreased Hb rsFC to brain regions implicated in motor, affective, cognitive, and pain inhibitory/modulatory processes may contribute to their symptomatology.

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

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 2 separate cross-sectional randomized experiments, 10 (6 female) unilateral CRPS patients wore prism glasses that laterally shifted the visual field by 20°. Skin temperature was measured before and after 9-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 analysis of variance and Wilcoxon 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.

Graded Motor Imagery and the Impact on Pain Processing in a Case of CRPS

Graded motor imagery (GMI) shows promising results for patients with complex regional pain syndrome (CRPS). In a case with chronic unilateral CRPS type I, we applied GMI for 6 weeks and recorded clinical parameters and cerebral activation using functional magnetic resonance imaging (fMRI; pre-GMI, after each GMI block, and after 6 mo). Changes in fMRI activity were mapped during movement execution in areas associated with pain processing. A healthy participant served as a control for habituation effects. Pain intensity decreased over the course of GMI, and relief was maintained at follow-up. fMRI during movement execution revealed marked changes in S1 and S2 (areas of discriminative pain processing), which seemed to be associated with pain reduction, but none in the anterior insula and the anterior cingulate cortex (areas of affective pain processing). After mental rotation training, the activation intensity of the posterior parietal cortex was reduced to one third. Our case report develops a design capable of differentiating cerebral changes associated with behavioral therapy of CRPS type I study.

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

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.