Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain

Chronic pain is often associated with reduced tactile acuity. A relationship exists between pain intensity, tactile acuity and cortical reorganisation. When pain resolves, tactile function improves and cortical organisation normalises. Tactile acuity can be improved in healthy controls when tactile stimulation is associated with a behavioural objective. We hypothesised that, in patients with chronic limb pain and decreased tactile acuity, discriminating between tactile stimuli would decrease pain and increase tactile acuity, but tactile stimulation alone would not. Thirteen patients with complex regional pain syndrome (CRPS) of one limb underwent a waiting period and then 2 weeks of tactile stimulation under two conditions: stimulation alone or discrimination between stimuli according to their diameter and location. There was no change in pain (100 mm VAS) or two-point discrimination (TPD) during a no-treatment waiting period, nor during the stimulation phase (p > 0.32 for both). Pain and TPD were lower after the discrimination phase [mean (95% CI) effect size for pain VAS = 27 mm (14–40 mm) and for TPD = 5.7 mm (2.9–8.5 mm), p < 0.015 for both]. These gains were maintained at three-month follow-up. We conclude that tactile stimulation can decrease pain and increase tactile acuity when patients are required to discriminate between the type and location of tactile stimuli.     

I can’t find it! Distorted body image and tactile dysfunction in patients with chronic back pain

The conscious sense of our body, or body image, is often taken for granted, but it is disrupted in many clinical states including complex regional pain syndrome and phantom limb pain. Is the same true for chronic back pain? Body image was assessed, via participant drawings, in six patients with chronic back pain and ten healthy controls. Tactile threshold and two-point discrimination threshold (TPD) were assessed in detail. All the patients, and none of the controls, showed disrupted body image of the back. Five patients were unable to clearly delineate the outline of their trunk and stated that they could not “find it”. TPD was greatly increased in the same zone as the absence or disruption of body image, but was otherwise similar to controls. The disturbance of body image and decrease in tactile acuity coincided with the normal distribution of pain, although there was no allodynia and there was no relationship between resting pain level and TPD. Tactile threshold was unremarkable for patients and controls. These preliminary data indicate that body image is disrupted, and tactile acuity is decreased, in the area of usual pain, in patients with chronic back pain. This finding raises the possibility that training body image or tactile acuity may help patients in chronic spinal pain, as it has been shown to do in patients with complex regional pain syndrome or phantom limb pain.     

Strength training improves fall-related gait kinematics in the elderly: A randomized controlled trial

Background

Falls are one of the greatest concerns among the elderly. Among a number of strategies proposed to reduce the risk of falls, improving muscle strength has been applied as a successful preventive strategy. Although it has been suggested as a relevant strategy, no studies have analyzed how muscle strength improvements affect the gait pattern. The aim of this study was to determine the effects of a lower limb strength training program on gait kinematics parameters associated with the risk of falls in elderly women.

Methods

Twenty seven elderly women were assigned in a balance and randomized order into an experimental (n = 14; age = 61.1 (4.3) years, BMI = 26.4 (2.8) kg m⁻²) and a control (n = 13; age = 61.6 (6.6) years; BMI = 25.9 (3.0) kg m⁻²) group. The EG performed lower limb strength training during 12 weeks (3 days per week), being training load increased weekly.

Findings

Primary outcomes were gait kinematics parameters and maximum voluntary isometric contractions at pre- and post-training period. Secondary outcomes were training load improvement weekly and one repetition maximum every two weeks. The 1 maximal repetition increment ranged from 32% to 97% and was the best predictor of changes in gait parameters (spatial, temporal and angular variables) after training for the experimental group. Z-score analysis revealed that the strength training was effective in reversing age-related changes in gait speed, stride length, cadence and toe clearance, approaching the elderly to reference values for healthy young women.

Interpretation

Lower limb strength training improves fall-related gait kinematic parameters. Thus, strength training programs should be recommended to the elderly women in order to change their gait pattern towards young adults.     

Show me the skin! Does seeing the back enhance tactile acuity at the back?

A growing body of literature associates musculoskeletal disorders with cortical reorganisation. One condition in which reorganisation is established and treatments that ‘train the brain’ are being widely used is chronic back pain. Recent evidence suggests that treatments that involve tactile training are more effective if they incorporate multisensory mechanisms, most obviously vision. With regard to back pain however, we must first determine if tactile function is enhanced by incorporating other modalities. A series of three cross-over experiments were conducted in healthy pain-free subjects to determine whether tactile acuity is enhanced when participants can see the skin of their back during testing. An initial randomised cross-over experiment suggested tactile acuity was significantly enhanced when participants could see their backs (t(25) = −4.226, p < 0.001, r = 0.65). However, a second replication experiment was not corroborative. Both the second (F(3,66) = 1.00, p = 0.398) and third (t(9) = 0.969, p = 0.358) experiments suggested that seeing the back did not significantly affect tactile acuity, confirming that our initial results were likely due to chance. The principle that visual feedback improves tactile acuity at the hand does not apply to the back. These results strongly suggest that attempts to enhance tactile training by incorporating vision will not offer the benefit to treatment of back pain that has been observed for treatment of hand pain.     

Tactile Precision Remains Intact When Acute Neck Pain Is Induced

A growing body of evidence suggests that chronic pain is associated with perceptual changes, such as impaired tactile acuity and laterality judgements. A recent study on low back pain showed that tactile acuity was decreased immediately after acute pain induction. Biologically, acute pain should lead to enhanced rather than disruptive changes in tactile acuity to meaningfully respond to potentially damaging nociceptive stimuli. In this double-blinded experiment, 30 healthy volunteers attended 3 experimental sessions (injection, sham injection, and control condition) separated by 1 week each, to investigate the effect of acute nociception on tactile precision and laterality judgements. In the real injection condition, acute pain was induced by hypertonic saline solution injected into the mid portion of the trapezius muscle. Tactile acuity (2-point discrimination and an estimation task) and laterality judgements were measured before and during pain perception. In the sham condition, the injection was mimicked by a sham procedure (without piercing the skin), and in the control condition no intervention took place. Results showed that tactile acuity remained intact (P = .92), indicating that experimentally induced neck pain did not affect tactile precision. The time needed to complete the laterality judgement task improved over time in all conditions, reflecting a learning effect (P = .05). We conclude that acute neck pain does not result in perceptual distortions, possibly reflecting a higher protection demand for the neck, a body region in close anatomic proximity to neural centers responsible for vital functions. These data—in the context of existing evidence—indicates that tactile acuity may respond differently to noxious stimulation in different anatomic regions.PerspectiveIn this study, a sensory adaptation to acute neck pain was investigated. It was found that experimental neck pain did not elicit changes in the sensory axis, leaving tactile acuity intact in otherwise healthy participants. These data support site-specific sensory adaptation to pain.     

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.     

Exploring the Relationships Between Altered Body Perception,Limb Position Sense,and Limb Movement Sense in Complex Regional Pain Syndrome

Chronic pain is often accompanied by patient-reported distorted body perception and an altered kinesthesia (referring to the senses of limb position and limb movement), but the association between these deficits is unknown. The objectives of this study were to assess body perception and the senses of limb position and limb movement in complex regional pain syndrome (CRPS) and to test whether these variables are related to each other and to pain intensity. Thirteen patients with upper limb CRPS (mean pain intensity, 4.2 ± 2.4 out of 10) and 13 controls were recruited. Body perception was self-reported with a questionnaire, and the senses of limb position (task 1) and of limb movement (task 2) were assessed with a robotic system combined with a 2D virtual reality display. The results showed altered kinesthesia in the patients with CRPS compared with controls (all P < .05). Moreover, in the CRPS group, greater pain intensity was associated with lower performance on task 2 (r?=?-.60; P < .05). Although alterations in participants’ sense of limb position and limb movement were associated with each other (r?=?-.70, P < .01), they were not related to the altered body perception (all P > .26). Therefore, the results suggest that kinesthesia and body perception should be considered and evaluated separately in patients with CRPS.

Is successful rehabilitation of complex regional pain syndrome due to sustained attention to the affected limb? A randomised clinical trial

In complex regional pain syndrome (CRPS1) initiated by wrist fracture, a motor imagery program (MIP), consisting of hand laterality recognition followed by imagined movements and then mirror movements, reduces pain and disability, but the mechanism of effect is unclear. Possibilities include sustained attention to the affected limb, in which case the order of MIP components would not alter the effect, and sequential activation of cortical motor networks, in which case it would. Twenty subjects with chronic CRPS1 initiated by wrist fracture and who satisfied stringent inclusion criteria, were randomly allocated to one of three groups: hand laterality recognition, imagined movements, mirror movements (RecImMir, MIP); imagined movements, recognition, imagined movements (ImRecIm); recognition, mirror movements, recognition (RecMirRec). At 6 and 18 weeks, reduced pain and disability were greater for the RecImMir group than for the other groups (P<0.05). Hand laterality recognition imparted a consistent reduction in pain and disability across groups, however, this effect was limited in magnitude. Imagined movements imparted a further reduction in pain and disability, but only if they followed hand laterality recognition. Mirror movements also imparted a reduction in pain and disability, but only when they followed imagined movements. The effect of the MIP seems to be dependent on the order of components, which suggests that it is not due to sustained attention to the affected limb, but is consistent with sequential activation of cortical motor networks.     

Decreased perceptual learning ability in complex regional pain syndrome

Recently, several functional imaging studies have shown that sensorimotor cortical representations may be changed in complex regional pain syndromes (CRPS). Therefore, we investigated tactile performance and tactile learning as indirect markers of cortical changes in patients with CRPS type I and controls. Patients had significant higher spatial discrimination thresholds at CRPS-affected extremities compared to both unaffected sides and control subjects. Furthermore, in order to improve tactile spatial acuity we used a Hebbian stimulation protocol of tactile coactivation. This consistently improved tactile acuity, both in controls and patients. However, the gain of performance was significantly lower on the CRPS-affected side implying an impaired perceptual learning ability. Therefore, we provide further support for an involvement of the CNS in CRPS, which may have implications to future neurorehabilitation strategies for this disease.     

Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome

In the complex regional pain syndrome (CRPS), several theories proposed the existence of pathophysiological mechanisms of central origin. Recent studies highlighted a smaller representation of the CRPS-affected hand on the primary somatosensory cortex (SI) during non-painful stimulation of the affected side. We addressed the question whether reorganizational changes can also be found in the secondary somatosensory cortex (SII). Moreover, we investigated whether cortical changes might be accompanied by perceptual changes within associated skin territories. Seventeen patients with CRPS of one upper limb without the presence of peripheral nerve injuries (type I) were subjected to functional magnetic resonance imaging (fMRI) during electrical stimulation of both index fingers (IFs) in order to assess hemodynamic signals of the IF representation in SI and SII. As a marker of tactile perception, we tested 2-point discrimination thresholds on the tip of both IFs. Cortical signals within SI and SII were significantly reduced contralateral to the CRPS-affected IF as compared to the ipsilateral side and to the representation of age- and sex-matched healthy controls. In parallel, discrimination thresholds of the CRPS-affected IF were significantly higher, giving rise to an impairment of tactile perception within the corresponding skin territory. Mean sustained, but not current pain levels were correlated with the amount of sensory impairment and the reduction in signal strength. We conclude that patterns of cortical reorganization in SI and SII seem to parallel impaired tactile discrimination. Furthermore, the amount of reorganization and tactile impairment appeared to be linked to characteristics of CRPS pain.     

Systematic review of the effectiveness of mirror therapy in upper extremity function

Purpose.?This review gives an overview of the current state of research regarding the effectiveness of mirror therapy in upper extremity function.

Method.?A systematic literature search was performed to identify studies concerning mirror therapy in upper extremity. The included journal articles were reviewed according to a structured diagram and the methodological quality was assessed.

Results.?Fifteen studies were identified and reviewed. Five different patient categories were studied: two studies focussed on mirror therapy after an amputation of the upper limb, five studies focussed on mirror therapy after stroke, five studies focussed on mirror therapy with complex regional pain syndrome type 1 (CRPS1) patients, one study on mirror therapy with complex regional pain syndrome type 2 (CRPS2) and two studies focussed on mirror therapy after hand surgery other than amputation.

Conclusions.?Most of the evidence for mirror therapy is from studies with weak methodological quality. The present review showed a trend that mirror therapy is effective in upper limb treatment of stroke patients and patients with CRPS, whereas the effectiveness in other patient groups has yet to be determined.     

Effects of body-weight supported treadmill training on kinetic symmetry in persons with chronic stroke

Background

The purpose was to examine changes in kinetic symmetry in persons with chronic stroke immediately and 6-months after body-weight supported treadmill training.

Methods

Fifteen participants at least six-months post stroke and able to ambulate between 0.4 and 0.8 m/s and 20 participants without neurological conditions completed all phases of the study and were included in the analysis. The non-disabled group served as a comparison for describing changes in kinetic symmetry. The stroke group completed 24 sessions of body-weight supported treadmill training over 8-weeks with 20 minutes of total walking per session. Bilateral 3-dimensional motion analysis and gait speed were assessed 1-week before training (pre-test), 1-week after training (post-test) and 6-months after training (retention) in a repeated measures design. Relative propulsion of the paretic leg and relative positive work of the hip, knee and ankle joints of both legs were calculated to evaluate symmetry of kinetic forces.

Findings

Statistically significant differences in relative propulsion and positive joint work within the paretic and non-paretic legs were not found over time. The stroke group significantly improved gait speed from pre- to post-test (p = .001) and pre-test to retention (p = .008). In comparison to the non-disabled group, forces produced by the stroke group were asymmetrical demonstrating compensatory adaptation.

Interpretation

Although the participants with chronic stroke walked faster after body-weight supported treadmill training, the relative percentages of propulsion and positive work remained unchanged. These findings suggest that the increase in speed was likely due to strengthening existing compensatory strategies rather than through recovery of normal kinetic symmetry.     

Wherever is my arm? Impaired upper limb position accuracy in Complex Regional Pain Syndrome

Knowledge of the position of one’s limbs is an essential component of daily function and relies on complex interactions of sensorimotor body schema-related information. Those with Complex Regional Pain Syndrome (CRPS) express difficulty in knowing where their affected limb is positioned. The aim of this study was to determine the degree to which experimental data supported the reported difficulty in limb position sense. A controlled experimental design was used to measure upper limb position accuracy amongst those with CRPS of one arm. Position accuracy was individually measured in both arms and compared to a known target position. Video captured each of 36 trials (half with arm in full view and half with vision obscured). The error in degrees between actual and known targets was determined using video analysis software. The Brief Pain Inventory measured pain. A subjective mental image representation of both upper limbs was documented. The CRPS group had moderate pain intensity and were significantly less accurate in positioning both the affected and unaffected limbs compared to controls (p < 0.001). Position accuracy of the CRPS affected limb significantly improved with vision (8.3° in view, 10.7° not in view). Subjective mental representations of the affected limb were visualised as distorted. Evidence of bilateral arm positioning impairments in unilateral arm CRPS suggests that central mechanisms are involved. Cortical reorganisation in regions associated with the body schema (i.e. primary somatosensory and parietal cortices) is proposed as an explanation. The exact relationship between pain and limb position deficits requires further exploration.     

Intact 2D-form recognition despite impaired tactile spatial acuity in complex regional pain syndrome type I

Tactile acuity measured by 2-point discrimination performance is impaired in patients with complex regional pain syndrome type I (CRPS-I). This is mirrored by pain-associated shrinkage of the cortical representation of the affected limb. We investigated whether, also, more complex tactile performance assessed by a dynamic 2D-form perception task is disturbed in CRPS-I patients. Therefore, we developed a Braille-like recognition task (BT) for geometrical dot pattern identification by dynamic touch. We studied 47 healthy volunteers (Study I) and compared them to 16 CRPS-I patients (Study II). Besides recognition time and error quote of the BT, we assessed static 2-point discrimination thresholds (TPDT). In healthy subjects, the performance in the BT correlated significantly with age and TPDT. In CRPS patients, TPDT was significantly increased on the affected side compared to sex- and age-matched controls from study I (2.98 ± 0.84 mm vs 2.05 ± 0.82 mm, P<0.01). The performance in the BT was not impaired in CRPS-I patients (compared to sex- and age-matched controls from study I) and was not correlated to the TPDT. The intact 2D-form recognition ability in CRPS-I patients might be explained by intact dynamic tactile and proprioceptive functions, which appear to be uncompromised by the impaired static tactile perception, provided that the spacing of the dot pattern is above the individual tactile acuity. These intact 2D-form perception capacities may also be related to higher sensory integration functions like the visual system and intact semantic understanding, which may be spared by the cortical reorganization phenomena in CRPS-I.     

Graded motor imagery is effective for long-standing complex regional pain syndrome: a randomised controlled trial

Complex regional pain syndrome type 1 (CRPS1) involves cortical abnormalities similar to those observed in phantom pain and after stroke. In those groups, treatment is aimed at activation of cortical networks that subserve the affected limb, for example mirror therapy. However, mirror therapy is not effective for chronic CRPS1, possibly because movement of the limb evokes intolerable pain. It was hypothesised that preceding mirror therapy with activation of cortical networks without limb movement would reduce pain and swelling in patients with chronic CRPS1. Thirteen chronic CRPS1 patients were randomly allocated to a motor imagery program (MIP) or to ongoing management. The MIP consisted of two weeks each of a hand laterality recognition task, imagined hand movements and mirror therapy. After 12 weeks, the control group was crossed-over to MIP. There was a main effect of treatment group (F(1, 11) = 57, P < 0.01) and an effect size of approximately 25 points on the Neuropathic pain scale. The number needed to treat for a 50% reduction in NPS score was approximately 2. The effect of treatment was replicated in the crossed-over control subjects. The results uphold the hypothesis that a MIP initially not involving limb movement is effective for CRPS1 and support the involvement of cortical abnormalities in the development of this disorder. Although the mechanisms of effect of the MIP are not clear, possible explanations are sequential activation of cortical pre-motor and motor networks, or sustained and focussed attention on the affected limb, or both.     

Altered Neurocognitive Processing of Tactile Stimuli in Patients with Complex Regional Pain Syndrome

Chronic pain in complex regional pain syndrome (CRPS) has been linked to tactile misperceptions and deficits in somatotopic representation of the affected limb. In this study, we identify altered cognitive processing of tactile stimuli in CRPS patients that we propose marks heterogeneity in tactile decision-making mechanisms. In a case-control design, we compared middle- and late-latency somatosensory evoked potentials in response to pseudorandomized mechanical stimulation of the digits of both hands (including CRPS-affected and nonaffected sides) between 13 CRPS patients and 13 matched healthy controls. During a task to discriminate the digit simulated, patients (compared with controls) had significantly lower accuracy and slowed response times but with high between-subject variability. At middle latencies (124–132?ms), tactile processing in patients relative to controls showed decrements in superior parietal lobe and precuneus (that were independent of task demands) but enhanced activity in superior frontal lobe (that were task-dependent). At late latencies, patients showed an augmented P300-like response under task demands that localized to the supplementary motor area. Source activity in the supplementary motor area correlated with slowed response times, although its scalp representation intriguingly correlated with better functioning of the affected limb, suggesting a compensatory mechanism. Future research should investigate the clinical utility of these putative markers of tactile decision-making mechanisms in CRPS.

Vergleichbare St?rung des K?rperschemas bei Patienten mit komplexem regionalem Schmerzsyndrom (CRPS) oder Phantomschmerz

In patients with complex regional pain syndrome (CRPS) a disruption of the body schema has been shown in an altered cortical representation of the hand and in delayed reaction times (RT) in the hand laterality recognition task. However, the role of attentional processes or the effect of isolated limb laterality training has not yet been clarified. The performance of healthy subjects (n = 38), CRPS patients (n = 12) and phantom limb pain (PLP) patients (n = 12) in a test battery of attentional performance (TAP) and in a limb laterality recognition task was compared and the effect of limb laterality training in CRPS patients and healthy subjects evaluated. The RTs of both CRPS and PLP patients were significantly slower than those of healthy subjects despite normal TAP values. The CRPS and PLP patients showed bilaterally delayed RTs. Through training RTs improved significantly but the RTs of CRPS patients remained slower than those of healthy subjects. In this study an equal disruption of the body schema was found in both CRPS and PLP patients which cannot be accounted for by attentional processes. For CRPS patients this disorder cannot be fully reversed by isolated limb laterality recognition training.     

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

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.     

The effects of neuromuscular training on the gait patterns of ACL-deficient men and women

Background

Anterior cruciate ligament rupture is the most common knee ligament injury sustained by active individuals, and the relative injury risk is sex-specific. Women not only demonstrate an increased risk for injury, but also a poorer response following ligament rupture. Perturbation training has shown positive results in healthy females, but gender-specific responses to training after injury have not been evaluated. The purpose of this investigation was to describe the effects of perturbation training on the gait characteristics of male and female non-copers.

Methods

Biomechanical data were collected before and after training on 12 male and nine female non-copers using standard motion analysis techniques. Subjects walked at a consistent, self-selected speed over an embedded force plate. Data from both limbs were post-processed and analyzed using a mixed model analysis of variance and minimal clinically important differences to compare the limb behaviors of men and women.

Findings

Prior to training, only women demonstrated significant hip joint excursion asymmetry (ES = 1.03; P = 0.009). Minimal clinically important difference values showed that the involved limb of the women had reduced hip and knee flexion angles and moments, truncated knee excursions, and increased hip excursions when compared to their own uninvolved limb and the limbs of the male non-copers. Following training, only knee extensor moment values exceeded the minimal clinically important differences in women.

Interpretation

Female non-copers demonstrated unique movement strategies following injury and perturbation training. Women may be a meaningful subgroup of non-copers, and future investigations should consider the effects of gender in the outcomes of non-copers.     

TNF-α in CRPS and 'normal' trauma--significant differences between tissue and serum

Posttraumatic TNF-alpha signaling may be one of the factors responsible for pain and hyperalgesia in complex regional pain syndromes (CRPS). In order to further specify the role of TNF-alpha we investigated tissue (skin) and serum concentrations in three different patient groups: patients with osteoarthritis and planned surgery, with acute traumatic upper limb bone fracture waiting for surgery, and with CRPS I. Thirty patients (10 in each group) were recruited. Mean CRPS duration was 36.1 ± 8.1 weeks (range 8-90 weeks). Skin punch biopsies were taken at the beginning of the surgery in osteoarthritis and fracture patients and from the affected side in CRPS patients. Blood samples were taken before the respective procedures. Skin and serum TNF-alpha levels were quantified by ELISA. Compared to patients with osteoarthritis, skin TNF-alpha was significantly elevated in CRPS (p < 0.001) and fracture patients (p < 0.04). Skin TNF-alpha in CRPS patients was higher than in patients with acute bone fracture (p < 0.02). In contrast, serum TNF-alpha values were the same in osteoarthritis and CRPS, and lower in fracture patients (p < 0.03). Our results indicate a local but not systemic increase of TNF-alpha in CRPS patients. This increase persists for months after limb trauma and may offer the opportunity for targeted treatment.