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.

Impaired predictability: enhanced fluctuations in the parenting behaviour of mothers of pre-school children with clinical diagnoses across three different play tasks.

Fluctuations in parenting behaviour are thought to be important for the development of child psychopathology. This study focusses on fluctuations in the parenting behaviour of mothers with 3-6-year-old children with a clinical diagnosis according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) (N = 39) and compared them with a control group of mothers with children without a clinical diagnosis (N = 41). In a laboratory setting, we compared the quality of mother-child interactions between both groups using three increasingly challenging co-operation tasks. At first, the mother and child interacted via a free play task. They then co-operated within a constructional play task and finally within a challenging problem-solving task. We analysed the mothers' parenting behaviour using the Laboratory Parenting Assessment Battery (LAB-PAB) and children's problem behaviours by means of their mothers' rating using the Child Behavior Checklist 1 ½-5 (CBCL). The results corroborated our hypotheses. Mothers of the group of children with clinical diagnoses had a lower parenting quality and higher fluctuations in parenting behaviour across situations compared with the non-clinical group. Further analysis revealed that specific fluctuations in maternal involvement and hostility uniquely predicted child psychopathology, measured with the CBCL, showing incremental validity of fluctuations in maternal involvement, when controlling for parenting quality and maternal difficulties in emotion regulation, measured with the Difficulties in Emotional Regulation scale. The results are discussed in terms of their implications for clinical interventions, as well as theoretical implications and future research.

[Body schema, multisensory integration and developmental disorders]. / Zum Zusammenhang zwischen Körperschema und sozio-emotionalem Verhalten bei umschriebenen Entwicklungsstörungen der Wahrnehmung und Motorik.

Our body is both, the object experiencing the world and the subject of our self- experience. As an object, the body provides sensory information via the bodily surface, which is processed and integrated into a coherent representation of the body, the body schema. This representation is considered to form a crucial structure underlying bodily self-identification. The process of integrating multimodal information into a coherent body representation has received extensive research interest with the aim to further clarify its neuronal correlates and functioning in health and disease. However, little is known about the ontogenetic functioning of body schema or multisensory integration processing and their role in the development of socio-emotional in children. This narrative overview discusses implication of a dysfunctional body schematic functioning for socio-emotional competencies. A general introduction on body schematic processes is followed by a narrative review of current findings on the maturation of the body schema and multisensory integration. We finally outline implications for the self- and socio-emotional development in children and discuss possible implications for a role of disrupted body schema functions in developmental disorders.

Changes of the Sensory Abnormalities and Cortical Excitability in Patients with Complex Regional Pain Syndrome of the Upper Extremity After 6 Months of Multimodal Treatment.

Objective: The most prominent sensory sign of the complex regional pain syndrome (CRPS) is blunt hyperalgesia, but longitudinal studies on its relation to the outcome of long-term multimodal treatment are lacking. Methods: We examined 24 patients with CRPS type I using standardized Quantitative Sensory Testing on the affected hand and the contralateral hand at baseline and 6 months following treatment. Somatosensory evoked potentials after single and paired-pulse stimulation of the median nerve were performed to assess the paired-pulse suppression (n = 19). Treatment response at follow-up was defined as pain relief > 30% and improved hand function. Statistics: Wilcoxon test, Pearson correlation. Results: At baseline, similar to previous studies, the pressure pain threshold (PPT) was significantly decreased and the pain response to repeated pinprick stimuli was significantly increased, while all detection thresholds were within the normal range without any difference between the later treatment responders and non-responders. After 6 months of treatment, the PPT increased significantly in the whole study group. However, the pressure hyperalgesia improved only in treatment responders (n = 17, P < 0.05), whereas there was no improvement in non-responders (n = 7). The rest of the sensory profile remained nearly unchanged. There was a correlation between the paired-pulse suppression and the PPT only at follow-up (r = 0.49, P < 0.05), but not at baseline, where low pressure pain threshold was associated with impaired paired-pulse suppression. Conclusion: Thus, the persistence of blunt hyperalgesia seems to be associated with impaired paired-pulse suppression, both representing maladaptive central nervous changes in CRPS, which may account for the treatment non-response in this subgroup.

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

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

The rubber hand illusion in complex regional pain syndrome: preserved ability to integrate a rubber hand indicates intact multisensory integration.

In patients with complex regional pain syndrome (CRPS) type 1, processing of static tactile stimuli is impaired, whereas more complex sensory integration functions appear preserved. This study investigated higher order multisensory integration of body-relevant stimuli using the rubber hand illusion in CRPS patients. Subjective self-reports and skin conductance responses to watching the rubber hand being harmed were compared among CRPS patients (N=24), patients with upper limb pain of other origin (N=21, clinical control group), and healthy subjects (N=24). Additionally, the influence of body representation (body plasticity [Trinity Assessment of Body Plasticity], neglect-like severity symptoms), and clinical signs of illusion strength were investigated. For statistical analysis, 1-way analysis of variance, t test, Pearson correlation, with α=0.05 were used. CRPS patients did not differ from healthy subjects and the control group with regard to their illusion strength as assessed by subjective reports or skin conductance response values. Stronger left-sided rubber hand illusions were reported by healthy subjects and left-side-affected CRPS patients. Moreover, for this subgroup, illness duration and illusion strength were negatively correlated. Overall, severity of neglect-like symptoms and clinical signs were not related to illusion strength. However, patients with CRPS of the right hand reported significantly stronger neglect-like symptoms and significantly lower illusion strength of the affected hand than patients with CRPS of the left hand. The weaker illusion of CRPS patients with strong neglect-like symptoms on the affected hand supports the role of top-down processes modulating body ownership. Moreover, the intact ability to perceive illusory ownership confirms the notion that, despite impaired processing of proprioceptive or tactile input, higher order multisensory integration is unaffected in CRPS.

Complex regional pain syndrome: more than a peripheral disease.

SUMMARY At early stages, complex regional pain syndrome (CRPS) is clinically characterized by damage of peripheral tissues and nerves (edema, activation of osteoblasts, hyperalgesia to blunt pressure). These signs are the result of a dysbalance of pro- and anti-inflammatory cytokines, which normalizes approximately 6 months after the beginning of the disease, independent from clinical outcome. At the same time, evolving clinical signs such as allodynia, cold hyperalgesia, reduced tactile acuity or symptoms of disrupted body representation (e.g., neglect-like syndrome, impaired hand laterality recognition or shift of the body midline) suggest a crucial role of the CNS in the pathophysiology of this pain syndrome. Imaging studies have found a severe but reversible reduction of the cortical hand representation (primary and secondary somatosensory cortices and primary motor cortices). Interestingly however, complex multisensory integration in central association areas are unaffected in CRPS, as patients are capable of integrating artificial body parts or recognize 2D forms despite tactile dysfunction. Furthermore, despite its unilateral clinical manifestation, it has been shown that in CRPS but not in other unilateral neuropathic pain syndromes, alterations in cortical excitability occur bilaterally, both in sensory and motor regions. In conclusion, a more widespread and bilateral pattern of CNS reorganization appears to characterize CRPS, which might be related to dysfunctions in the basal ganglia or in thalamo-cortical structures. Consequently, CRPS treatment should involve not only anti-inflammatory measures and pain therapy, but also the integration of neurorehabilitative training programs.

Impaired spatial body representation in complex regional pain syndrome type 1 (CRPS I).

UNLABELLED: Recently, a shift of the visual subjective body midline (vSM), a correlate of the egocentric reference frame, towards the affected side was reported in patients with complex regional pain syndrome (CRPS). However, the specificity of this finding is as yet unclear. This study compares 24 CRPS patients to 21 patients with upper limb pain of other origin (pain control) and to 24 healthy subjects using a comprehensive test battery, including assessment of the vSM in light and dark, line bisection, hand laterality recognition, neglect-like severity symptoms, and motor impairment (disability of the arm, shoulder, and hand). STATISTICS: 1-way analysis of variance, t-tests, significance level: 0.05. In the dark, CRPS patients displayed a significantly larger leftward spatial bias when estimating their vSM, compared to pain controls and healthy subjects, and also reported lower motor function than pain controls. For right-affected CRPS patients only, the deviation of the vSM correlated significantly with the severity of distorted body perception. Results confirm previous findings of impaired visuospatial perception in CRPS patients, which might be the result of the involvement of supraspinal mechanisms in this pain syndrome. These mechanisms might accentuate the leftward bias that results from a right-hemispheric dominance in visuospatial processing and is known as pseudoneglect. Pseudoneglect reveals itself in the tendency to perceive the midpoint of horizontal lines or the subjective body midline left of the centre. It was observable in all 3 groups, but most pronounced in CRPS patients, which might be due to the cortical reorganisation processes associated with this syndrome.

Left is where the L is right. Significantly delayed reaction time in limb laterality recognition in both CRPS and phantom limb pain patients.

The body schema is based on an intact cortical body representation. Its disruption is indicated by delayed reaction times (RT) and high error rates when deciding on the laterality of a pictured hand in a limb laterality recognition task. Similarities in both cortical reorganisation and disrupted body schema have been found in two different unilateral pain syndromes, one with deafferentation (phantom limb pain, PLP) and one with pain-induced dysfunction (complex regional pain syndrome, CRPS). This study aims to compare the extent of impaired laterality recognition in these two groups. Performance on a test battery for attentional performance (TAP 2.0) and on a limb laterality recognition task was evaluated in CRPS (n=12), PLP (n=12) and healthy subjects (n=38). Differences between recognising affected and unaffected hands were analysed. CRPS patients and healthy subjects additionally completed a four-day training of limb laterality recognition. Reaction time was significantly delayed in both CRPS (2278±735.7ms) and PLP (2301.3±809.3ms) compared to healthy subjects (1826.5±517.0ms), despite normal TAP values in all groups. There were no differences between recognition of affected and unaffected hands in both patient groups. Both healthy subjects and CRPS patients improved during training, but RTs of CRPS patients (1874.5±613.3ms) remain slower (p<0.01) than those of healthy subjects (1280.6±343.2ms) after four-day training. Despite different pathomechanisms, the body schema is equally disrupted in PLP and CRPS patients, uninfluenced by attention and pain and cannot be fully reversed by training alone. This suggests the involvement of complex central nervous system mechanisms in the disruption of the body schema.