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

BACKGROUND: Complex 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. METHODS: Forty-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. DISCUSSION: It 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).

Reduced Visuospatial Attention in Personal Space is Not Limited to the Affected Limb in Complex Regional Pain Syndrome.

Purpose: Alterations in spatial attention have been reported in people with chronic pain and may be relevant to understanding its cortical mechanisms and developing novel treatments. There is conflicting evidence as to whether people with Complex Regional Pain Syndrome (CRPS) have reduced visuospatial attention to their affected limb and/or its surrounding space, with some evidence that these deficits may be greater in personal (bodily) space. We aimed to test the competing hypotheses of whether the visuospatial attentional bias is specific to the personal space of the affected limb or generalizes to the personal space of other parts of the affected side of the body. Patients and Methods: Using visual Temporal Order Judgement tasks, we measured spatial attention in the personal space of the hands and feet of patients with upper (n=14) or lower (n=14) limb CRPS and pain-free controls (n=17). Participants judged the order of two light flashes presented at different temporal offsets on each of their hands or feet. Slower processing of the flash on one side relative to the other reflects reduced attention to that side of space. Results: Controls prioritized stimuli on the non-dominant (left) relative to dominant side, consistent with the well-documented normal leftward bias of attention (ie "pseudoneglect"). Regardless of the location (upper or lower limb) of the pain or visual stimuli, people with CRPS showed no such asymmetry, representing reduced attention to the affected side (compared to the greater attention of controls to their non-dominant side). More severe CRPS symptoms were associated with a greater tendency to deprioritize stimuli on the affected side. Conclusion: Our findings suggest that relative visuospatial bias in CRPS is generalized to the personal space of the affected side of the body, rather than being specific to the personal space of the CRPS-affected limb.

The sensorimotor theory of pathological pain revisited.

Harris (1999) proposed that pain can arise in the absence of tissue damage because changes in the cortical representation of the painful body part lead to incongruences between motor intention and sensory feedback. This idea, subsequently termed the sensorimotor theory of pain, has formed the basis for novel treatments for pathological pain. Here we review the evidence that people with pathological pain have changes to processes contributing to sensorimotor function: motor function, sensory feedback, cognitive representations of the body and its surrounding space, multisensory processing, and sensorimotor integration. Changes to sensorimotor processing are most evident in the form of motor deficits, sensory changes, and body representations distortions, and for Complex Regional Pain Syndrome (CRPS), fibromyalgia, and low back pain. Many sensorimotor changes are related to cortical processing, pain, and other clinical characteristics. However, there is very limited evidence that changes in sensorimotor processing actually lead to pain. We therefore propose that the theory is more appropriate for understanding why pain persists rather than how it arises.

Attention upturned: Bias toward and away from the affected side of the body and near space in a case of complex regional pain syndrome.

People with Complex Regional Pain Syndrome (CRPS) following limb injury can show neuropsychological symptoms in the absence of observable brain pathologies. These can include sensory changes, distorted body representation, and inattention to their affected limb and its surrounding space, resembling post-stroke hemispatial neglect. The precise nature and mechanisms of these neuropsychological symptoms are unclear, however insights could be gained by testing for dissociations and associations that have been observed in stroke patients. Drawing from clinical and experimental methods for investigating spatial attention bias and related symptoms in stroke patients, we conducted a detailed investigation of neuropsychological symptoms in a woman with CRPS of her left arm who initially presented to us with pronounced inattention to her affected side. The patient showed visual and tactile neglect and extinction on her affected side on confrontation tests, but no attention deficits on "bedside" tests of neglect. On sensitive computer-based measures, attention biases were found in the patient's body and near space (in Temporal Order Judgements), but not far or imagined space (on the Greyscales task and Mental Number Line Bisection). Unique to the current literature, the patient showed a reversal in her Temporal Order Judgement bias across time, from inattention (first and second session) to hyperattention (third session) to her affected side. In contrast, pain and self-reported body representation distortion were similar across the three sessions. The patient had reduced central and peripheral visual acuity, however these deficits were near symmetrical and therefore could not explain her performance on the visual attention tasks. Given that spatial attention bias has been linked to imbalance in relative activation of the two cerebral hemispheres, we administered a Global-Local processing task to test for hemispheric asymmetry. This revealed no difference in global compared to local interference refuting any hemispheric imbalance. Instead, the patient showed impaired performance (compared to controls) on incongruent trials regardless of trial type, consistent with executive impairment. We conclude that spatial attention bias in CRPS can generalize across different sensory modalities and extend beyond the affected limb to the external space around it, independent of any low-level sensory disturbances. This bias is not necessarily directed away from the affected side or stable over time. People with CRPS can also demonstrate more generalized neuropsychological changes in sensory and executive functions. Our observations refute several existing theories about the mechanisms of attention bias in CRPS, and their relationship to pain, and have potential implications for treatment.

Ignoring space around a painful limb? No evidence for a body-related visuospatial attention bias in complex regional pain syndrome.

BACKGROUND: Complex Regional Pain Syndrome (CRPS) is a disorder of severe chronic pain in one or more limb(s). People with CRPS report unusual perceptions of the painful limb suggesting altered body representations, as well as difficulty attending to their affected limb (i.e., a 'neglect-like' attention bias). Altered body representations and attention in CRPS might be related, however, existing evidence is unclear. We hypothesized that if there were a body-related visuospatial attention bias in CRPS, then any attention bias away from the affected side should be larger for or limited to circumstances when the (impaired) body representation is involved in the task versus when this is not the case. METHODS: We included 40 people with CRPS, 40 with other limb pain conditions, and 40 pain-free controls. In half of the people with pain, their upper limb was affected, in the other half their lower limb. We administered computerized tasks of spatial attention, including free viewing of images, shape cancellation, temporal order judgement, and dot-probe. The degree to which different versions of each task involved body representation was manipulated by one or more of the following: (1) presenting stimuli nearer versus further away from the body, (2) using body related versus neutral stimuli, and (3) inducing mental rotation of body parts versus no mental rotation. In addition to perceptual judgements, eye movements were recorded as a sensitive index of spatial attention. Bayesian repeated measures analyses were performed. RESULTS: We found no evidence for a (body-related) visuospatial attention bias in upper limb CRPS. Secondary analyses suggested the presence of a body-related visuospatial attention bias away from the affected side in some participants with lower limb CRPS. DISCUSSION: Our results add to growing evidence that there might be no general visuospatial attention bias away from the affected side in CRPS.

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

ABSTRACT: 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).

Normal manual straight ahead pointing in Complex Regional Pain Syndrome.

There is evidence to suggest that people with Complex Regional Pain Syndrome (CRPS) can have altered body representations and spatial cognition. One way of studying these cognitive functions is through manual straight ahead (MSA) pointing, in which participants are required to point straight ahead of their perceived body midline without visual feedback of the hand. We therefore compared endpoint errors from MSA pointing between people with CRPS (n = 17) and matched controls (n = 18), and examined the effect of the arm used (Side of Body; affected/non-dominant, non-affected/dominant). For all participants, pointing errors were biased towards the hand being used. We found moderate evidence of no difference between Groups on endpoint errors, and moderate evidence of no interaction with Side of Body. The differences in variability between Groups were non-significant/inconclusive. Correlational analyses showed no evidence of a relationship between MSA endpoint errors and clinical parameters (e.g. CRPS severity, duration, pain) or questionnaire measures (e.g. body representation, "neglect-like symptoms", upper limb disability). This study is consistent with earlier findings of no difference between people with CRPS and controls on MSA endpoint errors, and is the first to provide statistical evidence of similar performance of these two groups. Our results do not support a relationship between clinical or self-reported measures (e.g. "neglect-like symptoms") and any directional biases in MSA. Our findings may have implications for understanding neurocognitive changes in CRPS.

Validation of the Bath CRPS Body Perception Disturbance Scale.

The Bath Complex Regional Pain Syndrome Body Perception Disturbance Scale ("B-CRPS-BPDS") measures alterations in body perception. We assessed its internal consistency, known group validity, construct validity, and associations with demographic and clinical characteristics. We also evaluated changes in, and baseline predictors of B-CRPS-BPDS scores at follow-up. We included people with CRPS (N = 114) and pain-free controls (N = 69). People with CRPS obtained higher scores than pain-free controls on all B-CRPS-BPDS items, except the item on attention. Because this item also had an insufficient corrected item-total correlation, we propose a revised B-CRPS-BPDS (r-B-CRPS-BPDS) excluding this item. The internal consistency of the r-B-CRPS-BPDS was good. The r-B-CRPS-BPDS showed a large positive relationship with "motor neglect-like symptoms", indicating good construct validity. The r-B-CRPS-BPDS showed positive relationships with pain intensity, fear of movement, depression, and upper limb disability. There were no independent relationships with handedness, affected side, affected limb, disease duration, CRPS severity score, tension, anger, fatigue, confusion, and vigour. Finally, r-B-CRPS-BPDS scores did not consistently change over time. Our results demonstrate the utility of the r-B-CRPS-BPDS for measuring body perception disturbances in CRPS. PERSPECTIVE: This article evaluates the validity of the Bath Complex Regional Pain Syndrome Body Perception Disturbance Scale ("B-CRPS-BPDS") in CRPS, and assesses relationships with demographic and clinical variables. The proposed revised B-CRPS-BPDS appears to be a valid measure of body perception disturbances 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.

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.

Neuropsychological Changes in Complex Regional Pain Syndrome (CRPS).

Complex Regional Pain Syndrome (CRPS) is a poorly understood chronic pain condition of multifactorial origin. CRPS involves sensory, motor, and autonomic symptoms primarily affecting one extremity. Patients can also present with neuropsychological changes such as reduced attention to the CRPS-affected extremity, reminiscent of hemispatial neglect, yet in the absence of any brain lesions. However, this "neglect-like" framework is not sufficient to characterise the range of higher cognitive functions that can be altered in CRPS. This comprehensive literature review synthesises evidence of neuropsychological changes in CRPS in the context of potential central mechanisms of the disorder. The affected neuropsychological functions constitute three distinct but not independent groups: distorted body representation, deficits in lateralised spatial cognition, and impairment of non-spatially-lateralised higher cognitive functions. We suggest that many of these symptoms appear to be consistent with a broader disruption to parietal function beyond merely what could be considered "neglect-like." Moreover, the extent of neuropsychological symptoms might be related to the clinical signs of CRPS, and rehabilitation methods that target the neuropsychological changes can improve clinical outcomes in CRPS and other chronic pain conditions. Based on the limitations and gaps in the reviewed literature, we provide several suggestions to improve further research on neuropsychological changes in chronic 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.

Experimentally induced pain does not influence updating of peripersonal space and body representations following tool-use.

Representations of the body and peripersonal space can be distorted for people with some chronic pain conditions. Experimental pain induction can give rise to similar, but transient distortions in healthy individuals. However, spatial and bodily representations are dynamic, and constantly update as we interact with objects in our environment. It is unclear whether induced pain disrupts the mechanisms involved in updating these representations. In the present study, we sought to investigate the effect of induced pain on the updating of peripersonal space and body representations during and following tool-use. We compared performance under three conditions (pain, active placebo, neutral) on a visuotactile crossmodal congruency task and a tactile distance judgement task to measure updating of peripersonal space and body representations, respectively. Consistent with previous findings, the difference in crossmodal interference from visual distractors in the same compared to opposite visual field to the tactile target was less when tools were crossed than uncrossed. This suggests an extension of peripersonal space to incorporate the tips of the tools. Also consistent with previous findings, estimates of the felt tactile distance judgements decreased after active tool-use. In contrast to our predictions, however, we found no evidence that pain interfered with performance on either task when compared to the control conditions. Our findings suggest that the updating of peripersonal space and body representations is not disrupted by induced pain. That is, experiencing acute pain does not give rise to distorted representations of the body and peripersonal space that can be present in people with chronic pain conditions.

Dispositional Mindfulness and Psychological Health: a Systematic Review.

Interest in the influence of dispositional mindfulness (DM) on psychological health has been gathering pace over recent years. Despite this, a systematic review of this topic has not been conducted. A systematic review can benefit the field by identifying the terminology and measures used by researchers and by highlighting methodological weaknesses and empirical gaps. We systematically reviewed non-interventional, quantitative papers on DM and psychological health in non-clinical samples published in English up to June 2016, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A literature search was conducted using PsycINFO, PubMED, Medline and Embase, and 93 papers met the inclusion criteria. Within these, three main themes emerged, depicting the relationship between DM and psychological health: (1) DM appears to be inversely related to psychopathological symptoms such as depressive symptoms, (2) DM is positively linked to adaptive cognitive processes such as less rumination and pain catastrophizing and (3) DM appears to be associated with better emotional processing and regulation. These themes informed the creation of a taxonomy. We conclude that research has consistently shown a positive relationship between DM and psychological health. Suggestions for future research and conceptual and methodological limitations within the field are discussed.