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.</p

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

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.</p

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

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

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.</p

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

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