Upper-limb Complex Regional Pain Syndrome Research Articles

Fear of Movement in People with CRPS: A Psychometric Evaluation of the Tampa Scale-11 for Kinesiophobia.

People with complex regional pain syndrome (CRPS) commonly report a fear of movement that can worsen symptoms and increase disability. The Tampa Scale of Kinesiophobia (TSK) is used to evaluate fear of movement and (re)injury, but findings have been inconsistent in different populations. To evaluate the psychometric properties of the Persian version of TSK-11 in individuals with upper limb CRPS. Specifically, to determine if the factor structure aligns with the original two-factor model, consisting of "activity avoidance" and "somatic focus." People with CRPS (n=142, mean age=42, 54% female) completed the TSK. The psychometric testing included internal consistency and test-retest reliability (intra-class correlation coefficient), and convergent construct validity. Confirmatory and Exploratory factor analyses (CFA, EFA) were performed to evaluate the structural validity. The TSK-11 showed acceptable internal consistency (Cronbach alpha 0.93) and excellent test-retest reliability (ICC=0.93, 95% CI: 0.92 to 0.94). The Standard Error of Measurement and Minimal Detectable Change were 4.3 and 11.7, respectively. The results also demonstrated excellent criterion validity (r=0.81). CFA demonstrated that the original two-factor model did not fit. EFA derived a two-factor solution with different items. The factor structure accounted for 64.91% of the variance, and the internal consistency of the factors was acceptable (>0.90). Expert consensus suggested naming these two factors as Fear-avoidance, Magnification & Helplessness. The TSK-11 demonstrates excellent retest reliability in people with CRPS. The original two-factor structure was not confirmed, and a new 2-factor structure of the TSK-11 proposed consisting of subscales for Fear Avoidance beliefs and Magnification/Helplessness. Given the overlap between these constructs and the construct of pain catastrophizing, further study is needed to clarify both measures' content validity and relative uniqueness.

Somatotopic disruption of the functional connectivity of the primary sensorimotor cortex in complex regional pain syndrome type 1.

In complex regional pain syndrome (CRPS), the representation area of the affected limb in the primary sensorimotor cortex (SM1) reacts abnormally during sensory stimulation and motor actions. We recorded 3T functional magnetic resonance imaging resting-state data from 17 upper-limb CRPS type 1 patients and 19 healthy control subjects to identify alterations of patients' SM1 function during spontaneous pain and to find out how the spatial distribution of these alterations were related to peripheral symptoms. Seed-based correlations and independent component analyses indicated that patients' upper-limb SM1 representation areas display (i) reduced interhemispheric connectivity, associated with the combined effect of intensity and spatial extent of limb pain, (ii) increased connectivity with the right anterior insula that positively correlated with the duration of CRPS, (iii) increased connectivity with periaqueductal gray matter, and (iv) disengagement from the other parts of the SM1 network. These findings, now reported for the first time in CRPS, parallel the alterations found in patients suffering from other chronic pain conditions or from limb denervation; they also agree with findings in healthy persons who are exposed to experimental pain or have used their limbs asymmetrically. Our results suggest that CRPS is associated with a sustained and somatotopically specific alteration of SM1 function, that has correspondence to the spatial distribution of the peripheral manifestations and to the duration of the syndrome.

Experiences of diagnosis and treatment for upper limb Complex Regional Pain Syndrome: a qualitative analysis.

Complex Regional Pain Syndrome (CRPS) most frequently affects the upper limb, with high associated disability. Delays to diagnosis and appropriate treatment can adversely impact prognosis and quality of life, but little is known about the healthcare experiences of people with CRPS. This study aimed to explore lived experiences of diagnosis and treatment for people with upper limb CRPS. Participants were recruited through online support groups and multiple public and private healthcare settings in the Greater Wellington Region, New Zealand. Semi-structured interviews were conducted with participants who had experienced upper limb CRPS for more than three months and less than three years. Interviews were transcribed verbatim and analysed using reflexive thematic analysis. Thirteen participants (11 female, 2 male) aged between 43 and 68 years were interviewed. Duration of CRPS ranged from 7 months to 2.5 years. Five themes were identified. Participants initially engaged in healthcare out of a desire to return to being the person they were before having CRPS. Three interacting experiences epitomised the overall healthcare experience: (1) not knowing what is going on, (2) not being taken seriously, and (3) healthcare as adding another layer of load. Meanwhile, participants used multiple approaches in an attempt to not let CRPS stop them from continuing to live their lives. Participants in this study felt that credible information, validation, and simplification from healthcare providers and systems would support their process of navigating towards a meaningful life and self-concept in the presence of CRPS.

Efficacy of stellate ganglion interventions for complex regional pain syndrome in the upper limb-A systematic review and meta-analysis.

Stellate ganglion (SG) interventions for treating upper limb complex regional pain syndrome (CRPS) have been reported in studies. However, more substantial evidence is required to reach a consensus on its analgesic efficacy. To the best of our knowledge, no systematic review demonstrating the effectiveness of SG intervention for upper limb CRPS has been reported. Hence, this meta-analysis was done to ascertain the efficacy of SG intervention in managing patients with upper limb CRPS. A database search of PubMed, Cochrane, Embase, Scopus and Google Scholar was done for articles published between January 2001 and December 2021. Two independent reviewers extracted data from the included studies, and the studies were evaluated for any potential risk of bias, and a meta-analysis was performed. Eight studies were included in the qualitative synthesis, four were randomised controlled trials (RCTs), and the rest were non-RCTs. Six studies were assessed quantitatively. A significant reduction in pain scores post-intervention, up to two weeks, and four to 28 weeks after the procedure was observed, although the included studies exhibited marked heterogeneity. Qualitative analysis of these studies revealed an overall improvement in disability scores and functionality as assessed by an improved range of motion. Most studies reported no complications or only short-term minor complications after the procedure. Stellate ganglion interventions improve pain and disability scores with self-limiting short-term complications and no long-term complications. However, further studies with a large sample size are required to validate this treatment modality.

Characterizing biased visuospatial perception in complex regional pain syndrome.

Patients suffering from complex regional pain syndrome (CRPS) are increasingly shown to be affected by cognitive difficulties. While these cognitive symptoms were initially described as limited to the perception, representation and use of the body, that is, the somatic space, they were recently shown to also extend to the perception of extra-somatic space. CRPS patients seem indeed to pay less attention to visual stimuli occurring in the same side of space as their affected limb and especially those occurring close to that limb. The aim of the present study was to more precisely characterize these visuospatial biases, by investigating whether they may be dependent on the visually perceived proximity between the visual stimuli and the affected limb. Upper-limb CRPS patients and matched control participants performed temporal order judgements on visual stimuli, one presented in either side of space, while they could either see their hands near the visual stimuli or not. Visuospatial biases were not modulated by the availability of visual feedback about the hands. However, secondary analyses revealed that these biases depended on the type of rehabilitation program that the patients followed: whereas patients who did not follow any specific program presented significant biases to the detriment of visual stimuli in the affected side of space, patients who did follow a CRPS-specialized program did not. Patients' cognitive strategies will be important to consider when studying inter-individual differences in the cognitive symptomatology and associated cognitive-based rehabilitation procedures in CRPS. The existence of biases in visuospatial perception in Complex Regional Pain Syndrome has been reported but not always systematically replicated. We show that these biases might depend on the type of general rehabilitation program that the patients follow. Patients' individual cognitive strategies will be important to consider when studying the cognitive symptomatology of CRPS.

Person-centred management of upper limb complex regional pain syndrome: an integrative review of non-pharmacological treatment.

Complex Regional Pain Syndrome (CRPS) is most common in the upper limb and associated with high disability. The purpose of this review was to critically appraise and synthesise literature exploring non-pharmacological treatment for upper limb CRPS, to guide upper-limb-specific management. Using an integrative review methodology, 13 databases were searched to identify all published studies on non-pharmacological management of upper limb CRPS. The Crowe Critical Appraisal Tool was used to provide quality ratings for included studies, and analysis employed a qualitative descriptive approach. From 236 abstracts reviewed, 113 full texts were read, and 38 articles selected for data extraction. Designs included single case (n = 14), randomised controlled trial (n = 8), prospective cohort (n = 8), case series (n = 4), retrospective (n = 3), and mixed methods (n = 1). Interventions were categorised as sensory retraining (n = 13), kinesiotherapy (n = 7), manual therapies (n = 7), physical modalities (n = 6), and interdisciplinary treatment programmes (n = 5). All studies measured pain intensity, and most (n = 24) measured physical parameters such as strength, movement, or perceptual abilities. Few measured patient-rated function (n = 13) or psychological factors (n = 4). Quality ratings ranged from 30% to 93%, with a median of 60%. Methodological quality of non-pharmacological treatment approaches for upper limb CRPS is overall poor. Movement, desensitisation, and graded functional activity remain the mainstays of intervention. However, despite the impact of CRPS on wellbeing and function, psychological factors and functional outcomes are infrequently addressed. Further robust research is required to determine which aspects of treatment have the greatest influence on which symptoms, and when and how these should be introduced and progressed.

Atypical influence of biomechanical knowledge in Complex Regional Pain Syndrome-towards a different perspective on body representation

Part of the multifaceted pathophysiology of Complex Regional Pain Syndrome (CRPS) is ascribed to lateralized maladaptive neuroplasticity in sensorimotor cortices, corroborated by behavioral studies indicating that patients present difficulties in mentally representing their painful limb. Such difficulties are widely measured with hand laterality judgment tasks (HLT), which are also used in the rehabilitation of CRPS to activate motor imagery and restore the cortical representation of the painful limb. The potential of these tasks to elicit motor imagery is critical to their use in therapy, yet, the influence of the body’s biomechanical constraints (BMC) on HLT reaction time, supposed to index motor imagery activation, is rarely verified. Here we investigated the influence of BMC on the perception of hand postures and movements in upper-limb CRPS. Patients were slower than controls in judging hand laterality, whether or not stimuli corresponded to their painful hand. Reaction time patterns reflecting BMC were mostly absent in CRPS and controls. A second experiment therefore directly investigated the influence of implicit knowledge of BMC on hand movement judgments. Participants judged the perceived path of movement between two depicted hand positions, with only one of two proposed paths that was biomechanically plausible. While the controls mostly chose the biomechanically plausible path, patients did not. These findings show non-lateralized body representation impairments in CRPS, possibly related to difficulties in using correct knowledge of the body’s biomechanics. Importantly, they demonstrate the challenge of reliably measuring motor imagery with the HLT, which has important implications for the rehabilitation with these tasks.

Altered basal ganglia infraslow oscillation and resting functional connectivity in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a painful condition commonly accompanied by movement disturbances and often affects the upper limbs. The basal ganglia motor loop is central to movement, however, non‐motor basal ganglia loops are involved in pain, sensory integration, visual processing, cognition, and emotion. Systematic evaluation of each basal ganglia functional loop and its relation to motor and non‐motor disturbances in CRPS has not been investigated. We recruited 15 upper limb CRPS and 45 matched healthy control subjects. Using functional magnetic resonance imaging, infraslow oscillations (ISO) and resting‐state functional connectivity in motor and non‐motor basal ganglia loops were investigated using putamen and caudate seeds. Compared to controls, CRPS subjects displayed increased ISO power in the putamen contralateral to the CRPS affected limb, specifically, in contralateral putamen areas representing the supplementary motor area hand, motor hand, and motor tongue. Furthermore, compared to controls, CRPS subjects displayed increased resting connectivity between these putaminal areas as well as from the caudate body to cortical areas such as the primary motor cortex, supplementary and cingulate motor areas, parietal association areas, and the orbitofrontal cortex. These findings demonstrate changes in basal ganglia loop function in CRPS subjects and may underpin motor disturbances of CRPS.

P 84 Altered sensorimotor integration of afferent inhibition in patients with complex regional pain syndrome

Introduction: The complex regional pain syndrome (CRPS) is a chronic pain condition which frequently results in sensorimotor dysfunction of the affected limb. With respect to pathophysiology an impaired interaction in sensorimotor cortex has been hypothesized 1 . Sensorimotor interactions can be assessed through transcranial magnetic stimulation (TMS) that is preceded by an electrical stimulation of peripheral motor or sensory nerves (short/ long afferent inhibition; SAI/LAI). Previous studies revealed only minor alterations of LAI using peripheral motor stimulation in CRPS 2 . This study uses a more comprehensive assessment of SAI and LAI, induced by motor and sensory peripheral stimulation, to assess interaction of the sensorimotor system in CRPS. Methods : 13 unilateral upper limb affected patients with CRPS (9 females, 54 ± 17.8 years) and 11 controls (HCs; 8 females, 52± 18.3 years) received TMS on either hemisphere. SAI and LAI were induced by a motor (m_) or sensory (s_) median nerve stimulation preceded by TMS with 20ms (m_SAI) and 200ms (m_LAI) or 23ms (s_SAI) and 203ms (s_LAI), respectively 3 . Twenty paired and single TMS stimuli were randomly applied for each condition. Results: Pain levels were 5.1±1.5/10 at rest and 7.4±2.1/10 during movements. ANOVA revealed a significant group effect for patients vs. HCs on the affected side (F=2.2, p=0.048). Post hoc tests were corrected for multiple comparisons and showed reduced inhibition in patients after sensory stimulation (s_SAI: t=-2.51, p=0.04; s_LAI: t=-2.53 p=0.038) and motor stimulation with ISI 200ms (m_LAI: t=-2.62, p=0.032). Afferent sensorimotor inhibition was lower in patients with longer disease duration (r=-0.66, p=0.014). Discussion: We demonstrate altered sensorimotor integration of afferent inhibition in CRPS. Since afferent inhibition after sensory stimulation is thought to be mediated via interconnections especially between Brodmann area 3b of somatosensory and the motor cortex, our results complement existing literature about maladaptive cortical plasticity of these regions in CRPS 4,5 . Impairment in LAI, that is thought to involve higher-order somatosensory cortical areas and the posterior parietal cortex is in line with existing literature on chronic pain 2,4 . Future longitudinal investigation should evaluate intra- and intercortical sensorimotor integration systematically in CRPS to better understand their impact in development of sensorimotor symptoms. Literature: 1 Harris AJ. Cortical origins of pathological pain. Lancet 1999. 2 Morgante et al. Normal sensorimotor plasticity in complex regional pain syndrome with fixed posture of the hand. Mov Disord. 2017. 3 Sailer A, et al. Brain. 2003. 4 Chen et al. Modulation of motor cortex excitability by median nerve and digit stimulation. Exp Brain Res. 1999. 5 Pfannmöller et al. Investigations on maladaptive plasticity in the sensorimotor cortex of unilateral upper limb CRPS I patients. RNN. 2019.

Where is my arm? Investigating the link between complex regional pain syndrome and poor localisation of the affected limb.

BackgroundAnecdotally, people living with Complex Regional Pain Syndrome (CRPS) often report difficulties in localising their own affected limb when it is out of view. Experimental attempts to investigate this report have used explicit tasks and yielded varied results.MethodsHere we used a limb localisation task that interrogates implicit mechanisms because we first induce a compelling illusion called the Disappearing Hand Trick (DHT). In the DHT, participants judge their hands to be close together when, in fact, they are far apart. Sixteen volunteers with unilateral upper limb CRPS (mean age 39 ± 12 years, four males), 15 volunteers with non-CRPS persistent hand pain (‘pain controls’; mean age 58 ± 13 years, two males) and 29 pain-free volunteers (‘pain-free controls’; mean age 36 ± 19 years, 10 males) performed a hand-localisation task after each of three conditions: the DHT illusion and two control conditions in which no illusion was performed. The conditions were repeated twice (one for each hand). We hypothesised that (1) participants with CRPS would perform worse at hand self-localisation than both the control samples; (2) participants with non-CRPS persistent hand pain would perform worse than pain-free controls; (3) participants in both persistent pain groups would perform worse with their affected hand than with their unaffected hand.ResultsOur first two hypotheses were not supported. Our third hypothesis was supported —when visually and proprioceptively encoded positions of the hands were incongruent (i.e. after the DHT), relocalisation performance was worse with the affected hand than it was with the unaffected hand. The similar results in hand localisation in the control and pain groups might suggest that, when implicit processes are required, people with CRPS’ ability to localise their limb is preserved.

Intact tactile anisotropy despite altered hand perception in complex regional pain syndrome: rethinking the role of the primary sensory cortex in tactile and perceptual dysfunction.

Complex Regional Pain Syndrome (CRPS) is characterised by pain, autonomic, sensory and motor abnormalities. It is associated with changes in the primary somatosensory cortex (S1 representation), reductions in tactile sensitivity (tested by two-point discrimination), and alterations in perceived hand size or shape (hand perception). The frequent co-occurrence of these three phenomena has led to the assumption that S1 changes underlie tactile sensitivity and perceptual disturbances. However, studies underpinning such a presumed relationship use tactile sensitivity paradigms that involve the processing of both non-spatial and spatial cues. Here, we used a task that evaluates anisotropy (i.e., orientation-dependency; a feature of peripheral and S1 representation) to interrogate spatial processing of tactile input in CRPS and its relation to hand perception. People with upper limb CRPS (n = 14) and controls with (n = 15) or without pain (n = 19) judged tactile distances between stimuli-pairs applied across and along the back of either hand to provide measures of tactile anisotropy. Hand perception was evaluated using a visual scaling task and questionnaires. Data were analysed with generalised estimating equations. Contrary to our hypotheses, tactile anisotropy was bilaterally preserved in CRPS, and the magnitude of anisotropic perception bias was comparable between groups. Hand perception was distorted in CRPS but not related to the magnitude of anisotropy or bias. Our results suggest against impairments in spatial processing of tactile input, and by implication S1 representation, as the cause of distorted hand perception in CRPS. Further work is warranted to elucidate the mechanisms of somatosensory dysfunction and distorted hand perception in CRPS.

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.

Visual illusions modulate body perception disturbance and pain in Complex Regional Pain Syndrome: A randomized trial.

Effective treatment of longstanding Complex Regional Pain Syndrome (CRPS) is a challenge, as causal mechanisms remain elusive. People with CRPS frequently report distorted subjective perceptions of their affected limb. Evidence of pain reduction when the affected limb is visually altered in size suggests that visual illusions used to target central processing could restore coherence of this disrupted limb representation. We hypothesized that using virtual reality that alters hand image to match the patient's desired hand appearance would improve body perception disturbance and pain. Also, repeated exposure would maintain any therapeutic effect. A blinded randomized controlled trial of 45 participants with refractory upper-limb CRPS and body perception disturbance (BPD) viewed a digital image of their affected hand for 1min. The image was digitally altered according to the patient's description of how they desired their hand to look in the experimental group and unaltered in the control group. BPD and pain were measured pre- and post-intervention. A subgroup was followed up 2weeks after a course of repeated interventions. BPD (mean-6, ±SD 7.9, p=0.036, effect size [ES]=0.6) and pain intensity (mean-0.43, ±SD 1.3, p=0.047, ES=0.5) reduced in 23 participants after single exposure compared to controls (n=22). At follow-up, the subgroup (experimental n=21; control n=18) showed sustained pain reduction only (p=0.037, ±SD 1.9, ES=0.7), with an overall 1.2 decrease on an 11-point scale. Visually changing the CRPS hand to a desired appearance modulates BPD and pain suggesting therapeutic potential for those with refractory CRPS. Further research to optimize this therapeutic effect is required. Visual bodily illusions that change the shape and appearance of the painful CRPS hand to that desired by the patient result in a rapid amelioration of pain and body perception disturbance in people with longstanding CRPS. These findings highlight the future potential of this drug-free approach in the treatment of refractory CRPS.

Prism adaptation treatment for upper-limb complex regional pain syndrome: a double-blind randomized controlled trial.

Initial evidence suggested that people with complex regional pain syndrome (CRPS) have reduced attention to the affected side of their body and the surrounding space, which might be related to pain and other clinical symptoms. Three previous unblinded, uncontrolled studies showed pain relief after treatment with prism adaptation, an intervention that has been used to counter lateralised attention bias in brain-lesioned patients. To provide a robust test of its effectiveness for CRPS, we conducted a double-blind randomized controlled trial of prism adaptation for unilateral upper-limb CRPS-I. Forty-nine eligible adults with CRPS were randomized to undergo 2 weeks of twice-daily home-based prism adaptation treatment (n = 23) or sham treatment (n = 26). Outcomes were assessed in person 4 weeks before and immediately before treatment, and immediately after and 4 weeks after treatment. Long-term postal follow-ups were conducted 3 and 6 months after treatment. We examined the effects of prism adaptation vs sham treatment on current pain intensity and the CRPS symptom severity score (primary outcomes), as well as sensory, motor, and autonomic functions, self-reported psychological functioning, and experimentally tested neuropsychological functions (secondary outcomes). We found no evidence that primary or secondary outcomes differed between the prism adaptation and sham treatment groups when tested at either time point after treatment. Overall, CRPS severity significantly decreased over time for both groups, but we found no benefits of prism adaptation beyond sham treatment. Our findings do not support the efficacy of prism adaptation treatment for relieving upper-limb CRPS-I. This trial was prospectively registered (ISRCTN46828292).

Altered resting activity patterns and connectivity in individuals with complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder that typically occurs in the limbs, usually the upper limb. CRPS usually develops from a peripheral event but its maintenance relies on changes within the central nervous system. While functional abnormalities in the thalamus and primary somatosensory cortex (S1) of the brain are some of the most consistently reported brain findings in CRPS, the mechanisms are yet to be explored in full, not least of all how these two regions interact and how they might relate to clinical deficits, such as the commonly reported poor tactile acuity in this condition. This study recruited 15 upper‐limb CRPS subjects and 30 healthy controls and used functional magnetic resonance imaging (fMRI) to investigate infra‐slow oscillations (ISOs) in critical pain regions of the brain in CRPS. As hypothesised, we found CRPS was associated with increases in resting signal intensity ISOs (0.03–0.06 Hz) in the thalamus contralateral to the painful limb in CRPS subjects. Interestingly, there was no such difference between groups in S1, however CRPS subjects displayed stronger thalamo‐S1 functional connectivity than controls, and this was related to pain. As predicted, CRPS subjects displayed poor tactile acuity on the painful limb which, interestingly, was also related to thalamo‐S1 functional connectivity strength. Our findings provide novel evidence of altered patterns of resting activity and connectivity in CRPS which may underlie altered thalamocortical loop dynamics and the constant perception of pain.

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.

Pain reduction by inducing sensory-motor adaptation in Complex Regional Pain Syndrome (CRPS PRISMA): protocol for a double-blind randomized controlled trial

BackgroundComplex Regional Pain Syndrome (CRPS) presents as chronic, continuous pain and sensory, autonomic, and motor abnormalities affecting one or more extremities. People with CRPS can also show changes in their perception of and attention to the affected body part and sensory information in the affected side of space. Prism Adaptation (PA) is a behavioural intervention targeted at reducing attention deficits in post-stroke hemispatial neglect. PA also appears to reduce pain and other CRPS symptoms; however, these therapeutic effects have been demonstrated only in small unblinded studies. This paper describes the protocol for an ongoing double-blind, randomized, sham-controlled clinical trial that will evaluate the efficacy of PA treatment for CRPS. The secondary aims of the study are to examine the relationships between neuropsychological changes (such as spatial attention, space and body representation, and motor spatial performance) and clinical manifestations of CRPS, as well as symptom improvement.MethodsForty-two participants with upper-limb CRPS type I will undergo 2 weeks of twice-daily PA treatment or sham treatment. The primary outcome measures are current pain intensity and CRPS severity score, measured immediately before and after the treatment period. Secondary outcome measures include the results of self-report questionnaires about pain, movement, symptoms interference, and body representation; clinical assessments of sensory, motor, and autonomic functions; and computer-based psychophysical tests of neuropsychological functions. Data are collected in four research visits: 4 weeks and 1 day before treatment, and 1 day and 4 weeks after the end of treatment. Additional follow-up through postal questionnaires is conducted 3 and 6 months post-treatment.DiscussionIt is hypothesised that participants undergoing PA treatment, compared to those receiving sham treatment, will show greater reduction in pain and CRPS severity score, and improvements on other clinical and neuropsychological measures. Also, more pronounced neuropsychological symptoms are predicted to correlate with more severe clinical CRPS symptoms. This study will provide the first randomized double-blind evaluation of the therapeutic effects of PA that could be implemented as a rehabilitation method for CRPS, and will contribute to the understanding of how neuropsychological changes in body representation and attention pertain to the manifestation and treatment of CRPS.Trial registration(27/03/2017): ISRCTN46828292 (ISRCTN - ISRCTN46828292: Treatment of complex regional pain syndrome (CRPS) with sensory-motor adaptation).

CRPS Is Not Associated with Altered Sensorimotor Cortex GABA or Glutamate.

Complex regional pain syndrome (CRPS) is a debilitating chronic pain disorder typically in the upper or lower limbs. While CRPS usually develops from a peripheral event, it is likely maintained by CNS changes. Indeed, CRPS is reported to be associated with sensorimotor cortex changes, or functional “reorganization,” as well as deficits such as poor tactile acuity. While the mechanisms underpinning cortical reorganization in CRPS are unknown, some have hypothesized that it involves disinhibition (i.e., a reduction in GABA activity). In this study, we addressed this hypothesis by using edited magnetic resonance spectroscopy to determine sensorimotor GABA and glutamate concentrations in 16 humans with CRPS and 30 matched control subjects and the relationship of these concentrations with tactile acuity. We found that individuals with upper limb CRPS displayed reduced tactile acuity in the painful hand, compared with the nonpainful hand and pain-free control subjects. Despite this acuity deficit, CRPS was not associated with altered GABA or glutamate concentrations within the sensorimotor cortex on either the side that represents the affected or unaffected hand. Furthermore, there was no significant relationship between sensorimotor GABA or glutamate concentrations and tactile acuity in CRPS subjects or control subjects. Although our sample was small, these data suggest that CRPS is not associated with altered total sensorimotor GABA or glutamate concentrations. While these results are at odds with the sensorimotor cortex disinhibition hypothesis, it is possible that GABAergic mechanisms other than total GABA concentration may contribute to such disinhibition.

Investigations on maladaptive plasticity in the sensorimotor cortex of unilateral upper limb CRPS I patients.

Patients with a complex regional pain syndrome (CRPS) in the upper limb show a sensory and motor impairment of the hand. Decreased intra-cortical-inhibition (ICI) of the motor representation of the affected hand muscle and decreased somatosensory hand representation size were related to maladaptive plasticity. To achieve new insights about CRPS we examined whether these alterations were present in a single cohort. We used a multi-modal approach comprising behavioral testing, transcranial magnetic stimulation, and high resolution fMRI combined with a new analysis technique for improved neuronal specificity. We found a decreased pinch-grip performance, two-point discrimination on the fingertips, ICI in the motor cortex, and representation size of the hand in Brodmann Area 3b (BA3b) in the somatosensory cortex. Our analysis further showed that correlations with ICI on the non-affected side were absent on the affected side. This study is the first to gather behavioral, neurophysiologic and imaging measurements for one patient cohort and it therefore enables a comprehensive view of collapsed associations of function and representation focused on the hemisphere contralateral to the affected hand.