Upper-limb Complex Regional Pain Syndrome Research Articles

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. PerspectiveSenses of limb position and movement rely on sensorimotor integration. Both are altered in complex regional pain syndrome. However, they are not related to the subjective perception of the painful limb, and thus they should be assessed separately in rehabilitation.

Biased visuospatial perception in complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a chronic pain condition associating sensory, motor, trophic and autonomic symptoms in one limb. Cognitive difficulties have also been reported, affecting the patients’ ability to mentally represent, perceive and use their affected limb. However, the nature of these deficits is still a matter of debate. Recent studies suggest that cognitive deficits are limited to body-related information and body perception, while not extending to external space. Here we challenge that statement, by using temporal order judgment (TOJ) tasks with tactile (i.e. body) or visual (i.e. extra-body) stimuli in patients with upper-limb CRPS. TOJ tasks allow characterizing cognitive biases to the advantage of one of the two sides of space. While the tactile TOJ tasks did not show any significant results, significant cognitive biases were observed in the visual TOJ tasks, affecting mostly the perception of visual stimuli occurring in the immediate vicinity of the affected limb. Our results clearly demonstrate the presence of visuospatial deficits in CRPS, corroborating the cortical contribution to the CRPS pathophysiology, and supporting the utility of developing rehabilitation techniques modifying visuospatial abilities to treat chronic pain.

Abnormal Brain Responses to Action Observation in Complex Regional Pain Syndrome.

This article shows that in CRPS, the observation of others' motor actions induces abnormal neural activity in brain areas essential for sensorimotor functions and pain. These results build the cerebral basis for action-observation impairments in CRPS.

Cortical reorganization of the healthy hand in upper-limb complex regional pain syndrome (CRPS): Is reorganizations of common beliefs about CRPS necessary?

Cortical reorganization of the healthy hand in upper-limb complex regional pain syndrome (CRPS) : Is reorganizations of common beliefs about CRPS necessary?

An exploration into the cortical reorganisation of the healthy hand in upper-limb complex regional pain syndrome

Background and aimsRecent evidence demonstrated that complex regional pain syndrome (CRPS) is associated with a larger than normal somatosensory (S1) representation of the healthy hand. The most intuitive mechanism for this apparent enlargement is increased, i.e. compensatory, use of the healthy hand. We investigated whether enlargement of the S1 representation of the healthy hand is associated with compensatory use in response to CRPS. Specifically, we were interested in whether the size of the S1 representation of the healthy hand is associated with the severity of functional impairment of the CRPS-affected hand. We were also interested in whether CRPS duration might be positively associated with the size of the representation of the healthy hand in S1. MethodsUsing functional magnetic resonance imaging (fMRI) data from our previous investigation, the size of the S1 representation of the healthy hand in CRPS patients (n=12) was standardised to that of a healthy control sample (n=10), according to hand dominance. Responses to questionnaires on hand function, overall function and self-efficacy were used to gather information on hand use in participants. Multiple regression analyses investigated whether the S1 representation was associated with compensatory use. We inferred compensatory use with the interaction between reported use of the CRPS-affected hand and (a) reported overall function, and (b) self-efficacy. We tested the correlation between pain duration and the size of the S1 representation of the healthy hand with Spearman's rho. ResultsThe relationship between the size of the S1 representation of the healthy hand and the interaction between use of the affected hand and overall function was small and non-significant (β=−5.488×10−5, 95% C.I. −0.001, 0.001). The relationship between the size of the S1 representation of the healthy hand and the interaction between use of the affected hand and self-efficacy was also small and non-significant (β=−6.027×10−6, 95% C.I. −0.001, 0.001). The S1 enlargement of the healthy hand was not associated with pain duration (Spearman's rho=−0.14, p=0.67). ConclusionOur exploration did not yield evidence of any relationship between the size of the healthy hand representation in S1 and the severity of functional impairment of the CRPS-affected hand, relative to overall hand use or to self-efficacy. There was also no evidence of an association between the size of the healthy hand representation in S1 and pain duration. The enlarged S1 representation of the healthy hand does not relate to self-reported function and impairment in CRPS. ImplicationsWhile this study had a hypothesis-generating nature and the sample was small, there were no trends to suggest compensatory use as the mechanism underlying the apparent enlargement of the healthy hand in S1. Further studies are needed to investigate the possibility that inter-hemispheric differences seen in S1 in CRPS may be present prior to the development of the disorder.

Predictors of Long-Term Outcome of Thoracic Sympathectomy in Patients with Complex Regional Pain Syndrome Type 2

Long-term results of sympathectomy in patients with complex regional pain syndrome (CRPS) type 2 varies widely among studies due to nonspecific or vague criteria of diagnosis and absence of outcome predictors that help good patient selection. The objective was to determine the predictors of long-term outcome of sympathectomy in patients with upper limb CRPS type2. A retrospective cohort, in which those who underwent thoracic sympathectomy for upper limb CRPS type 2 from 2007 to 2014, were included. Demographic andclinical data of patients, in addition to stellate ganglion block (SGB) details and percent of pain relief at the end of follow-up, were collected and used for statistical analysis. Our study included 53 patients, with a mean age of 47 ± 7 years, and 60% females. Using bivariate correlations; age, sex, nerve injured, type of injury, and occupation were not significantly correlated to outcome. Multiple linear regression analysis of correlated variables revealed that duration of pain relief after SGB and degree of sympathetic overactivity were positive predictors (β= 0.286, P= 0.027, and β= 0.257, P= 0.003, respectively), whereas presence of allodynia was a negative predictor (β=-0.280, P= 0.041) of thefinal pain relief. Final pain relief was better in those patients who experienced extended relief of their pain >2days after SGB (P= 0.001, Kruskal Wallis test). Thoracic sympathectomy may prove more effective than reported in carefully selected CRPS patients with prominent sympathetic overactivity, no or early allodynia, and pain relief >2 days after SGB.

Patients with complex regional pain syndrome overestimate applied force in observed hand actions.

Movement accuracy is ensured by interaction between motor, somatosensory, and visual systems. In complex regional pain syndrome (CRPS), this interaction is disturbed. To explore CRPS patients' visual perception of actions, we investigated how these patients evaluate the applied force in observed hand actions of another person. Nineteen patients suffering from unilateral upper-limb CRPS and 19 healthy control subjects viewed six different videos of left- and right-hand actions. They were asked to evaluate the applied force in each hand action, as well as their subjective sensations of unpleasantness and pain during the observation. The patients overestimated the force applied in the videos: the ratings were two times as large as in the control subjects for actions performed with the hand corresponding to the patients' affected hand, and 1.5 times as large for actions corresponding to their healthy hand. The control subjects considered the stimuli neutral and painless, whereas the patients rated them unpleasant. Moreover, the patients felt increased pain during viewing actions performed with the hand corresponding to their affected side. The overestimation of force was related to the elicited unpleasantness and pain, but not to the patients' muscle strength. We propose that the overestimation of force is explained both by the pain elicited by the observation and by the abnormal sensorimotor integration that is associated with perception of increased effort. This visually elicited unpleasantness and painfulness may promote avoidance of viewing own actions, further impairing the patients' motor performance.

Interhemispheric somatosensory differences in chronic pain reflect abnormality of the healthy side.

It is widely accepted that complex regional pain syndrome (CRPS) is associated with shrinkage of the primary somatosensory cortex (S1) representation of the affected limb. However, supporting evidence is surprisingly limited and may be compromised by high risk of bias. This study compared the S1 spatial representation of the hand in 17 patients with upper-limb CRPS to 16 healthy controls, using functional MRI. Innocuous vibration was delivered to digits one (D1) and five (D5) in a block-design. Resultant activation maxima were located within a bilateral S1 mask, determined a priori. Distance between D1 and D5 activation maxima, calculated for both hands, was used as a measure of S1 representation. Analyses were blinded to group and hand. In patients, S1 representation was smaller for the affected hand than it was for the healthy hand (t(11) = 2.02, P = 0.03), as predicted. However, S1 representation of the affected hand was no different to that of either hand in controls. Critically, S1 representation of the healthy hand of patients was larger than that of controls' hands. CRPS seems to be associated with an enlarged representation of the healthy hand, not a smaller representation of the affected hand. These findings raise important questions about neuroplasticity in CRPS.

Bilateral Hypersensitivity to Capsaicin, Thermal, and Mechanical Stimuli in Unilateral Complex Regional Pain Syndrome

Complex regional pain syndrome is multifactorial. Exaggerated inflammatory responses to limb injury may be involved. The authors hypothesized that capsaicin-induced pain and neurogenic inflammation (skin perfusion and flare area) are increased in patients with complex regional pain syndrome compared with that in controls. Twenty patients with unilateral upper-limb complex regional pain syndrome and 20 age-, sex-, and body mass index-matched controls participated. Topical capsaicin 5% was applied to the back of both hands for 30 min, and pain intensity was assessed on a visual analogue scale. A laser Doppler perfusion imager scanner estimated capsaicin-induced skin perfusion and flare area. Autonomic and small-fiber function was assessed by sensory testing, quantitative sudomotor axon reflex test, and vasoconstrictor responses. The authors found bilateral hypersensitivity to capsaicin (P ≤ 0.02), skin fold (P = 0.001), joint pressure (P < 0.0001), cold (P ≤ 0.01), and heat pain (P ≤ 0.04) in patients compared with that in controls and thermal and mechanical hyperalgesia in the complex regional pain syndrome-affected hand compared with that in the unaffected hand (P ≤ 0.001). The patients had normal capsaicin-induced flare areas, thermal detection thresholds, quantitative sudomotor axon reflex test, and vasoconstrictor responses. The main finding is bilaterally increased capsaicin-induced pain in patients compared with controls. The flare response to capsaicin was normal, suggesting that the increased pain response was not due to increased neurogenic inflammation. The bilateral hypersensitivity to painful chemical, thermal, and mechanical stimuli not confined to the innervation area of a peripheral nerve or root cannot be explained by a regional change and may partly be due to central sensitization.

Limb-specific autonomic dysfunction in complex regional pain syndrome modulated by wearing prism glasses

In unilateral upper-limb complex regional pain syndrome (CRPS), the temperature of the hands is modulated by where the arms are located relative to the body midline. We hypothesized that this effect depends on the perceived location of the hands, not on their actual location, nor on their anatomical alignment. In 2 separate cross-sectional randomized experiments, 10 (6 female) unilateral CRPS patients wore prism glasses that laterally shifted the visual field by 20°. Skin temperature was measured before and after 9-minute periods in which the position of one hand was changed. Placing the affected hand on the healthy side of the body midline increased its temperature (Δ°C=+0.47±0.14°C), but not if prism glasses made the hand appear to be on the body midline (Δ°C=+0.07±0.06°C). Similarly, when prism glasses made the affected hand appear to be on the healthy side of the body midline, even though it was not, the affected hand warmed up (Δ°C=+0.28±0.14°C). When prism glasses made the healthy hand appear to be on the affected side of the body midline, even though it was not, the healthy hand cooled down (Δ°C=−0.30±0.15°C). Friedman’s analysis of variance and Wilcoxon pairs tests upheld the results (P<0.01 for all). We conclude that, in CRPS, cortical mechanisms responsible for encoding the perceived location of the limbs in space modulate the temperature of the hands.

Appearance of Burning Abdominal Pain During Cesarean Section Under Spinal Anesthesia in a Patient with Complex Regional Pain Syndrome: A Case Report

The mechanism of complex regional pain syndrome (CRPS) was reported as being related to both the central and peripheral nervous systems. Recurrence of CRPS was, reportedly, induced by hand surgery in a patient with upper limb CRPS. However, there is no documentation of mechanical allodynia and burning abdominal pain induced by Cesarean section under spinal anesthesia in patients with upper limb CRPS. We report the case of a patient who suffered from burning abdominal pain during Cesarean section under spinal anesthesia 13 years after the occurrence of venipuncture-induced CRPS of the upper arm. The patient's pain characteristics were similar to the pain characteristics of her right arm during her previous CRPS episode 13 years earlier. In addition, mechanical allodynia around the incision area was confirmed after surgery. We provided ultrasound-guided rectus sheath block using 20 mL of 0.4% ropivacaine under ultrasound guidance twice, which resulted in the disappearance of the spontaneous pain and allodynia. The pain relief was probably related to blockade of the peripheral input by this block, which in turn would have improved her central sensitization. Our report shows that attention should be paid to the appearance of neuropathic pain of the abdomen during Cesarean section under spinal anesthesia in patients with a history of CRPS.

Uso da lidocaína tópica a 4% para terapia ocupacional em pacientes com síndrome dolorosa complexa regional: relato de casos

JUSTIFICATIVA E OBJETIVOS: A sindrome dolorosa complexa regional (SDCR) e uma desordem do sistema nervoso central com disfuncao simpatica. Sua fisiopatologia nao esta esclarecida. Perifericamente ha inflamacao e hipoxia. A dor traz angustia para o paciente. O objetivo deste estudo foi relatar e avaliar o uso da lidocaina topica a 4% durante a terapia ocupacional em pacientes ambulatoriais com SDCR. RELATO DOS CASOS: Foram estudados 5 pacientes, com idades acima de 18 anos, com SDCR tipo I e II de membro superior, avaliados em 6 consultas, com intervalos de 7 dias entre elas. Na primeira eram medicados com gabapentina e nas 5 posteriores a dose era aumentada. A partir da segunda consulta era utilizada a lidocaina a 4% topica cerca de 30 minutos antes da realizacao dos exercicios de reabilitacao do membro. Em 4 pacientes a SDCR era do tipo I. Em ordem decrescente os sintomas referidos foram: fisgada, queimacao, alodinia, choque e parestesia. Todos os pacientes apresentavam edema e disfuncao motora. Com a lidocaina topica a 4% foi possivel a realizacao dos exercicios orientados pelo terapeuta ocupacional, em regime ambulatorial, ocorrendo reducao significativa da intensidade da dor. CONCLUSAO: A lidocaina topica a 4% permitiu a realizacao da reabilitacao ocorrendo reducao significativa da intensidade da dor.

Morphine and Memantine Treatment of Long-Standing Complex Regional Pain Syndrome: Table 1

Dear Editor: Long-standing complex regional pain syndrome (CRPS) is difficult to treat and an effective oral regimen would be welcome. A recent randomized controlled trial in long-standing upper limb CRPS reported by Gustin et al. demonstrated significant pain relief, with minimal side effects in 10 patients, with an oral combination treatment of morphine and memantine [1]. Pain at rest/on movement was reduced by half or greater in 60%/70% of patients. Fifty percent of participants were male, and 60% had CRPS II. These characteristics are not typical for patients seen at our center. I …

Complex Interaction of Sensory and Motor Signs and Symptoms in Chronic CRPS

Spontaneous pain, hyperalgesia as well as sensory abnormalities, autonomic, trophic, and motor disturbances are key features of Complex Regional Pain Syndrome (CRPS). This study was conceived to comprehensively characterize the interaction of these symptoms in 118 patients with chronic upper limb CRPS (duration of disease: 43±23 months). Disease-related stress, depression, and the degree of accompanying motor disability were likewise assessed. Stress and depression were measured by Posttraumatic Stress Symptoms Score and Center for Epidemiological Studies Depression Test. Motor disability of the affected hand was determined by Sequential Occupational Dexterity Assessment and Michigan Hand Questionnaire. Sensory changes were assessed by Quantitative Sensory Testing according to the standards of the German Research Network on Neuropathic Pain. Almost two-thirds of all patients exhibited spontaneous pain at rest. Hand force as well as hand motor function were found to be substantially impaired. Results of Quantitative Sensory Testing revealed a distinct pattern of generalized bilateral sensory loss and hyperalgesia, most prominently to blunt pressure. Patients reported substantial motor complaints confirmed by the objective motor disability testings. Interestingly, patients displayed clinically relevant levels of stress and depression. We conclude that chronic CRPS is characterized by a combination of ongoing pain, pain-related disability, stress and depression, potentially triggered by peripheral nerve/tissue damage and ensuing sensory loss. In order to consolidate the different dimensions of disturbances in chronic CRPS, we developed a model based on interaction analysis suggesting a complex hierarchical interaction of peripheral (injury/sensory loss) and central factors (pain/disability/stress/depression) predicting motor dysfunction and hyperalgesia.

16. Complex Regional Pain Syndrome

AbstractComplex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy is a pain syndrome with an unclear pathophysiology and unpredictable clinical course. The disease is often therapy resistant, the natural course not always favorable. The diagnosis of CRPS is based on signs and symptoms derived from medical history and physical examination. Pharmacological pain management and physical rehabilitation of limb function are the main pillars of therapy and should be started as early as possible. If, however, there is no improvement of limb function and persistent severe pain, interventional pain management techniques may be considered.Intravenous regional blocks with guanethidine did not prove superior to placebo but frequent side effects occurred.Therefore this technique receives a negative recommendation (2 A–). Sympathetic block is the interventional treatment of first choice and has a 2 B+ rating. Ganglion stellatum (stellate ganglion) block with repeated local anesthetic injections or by radiofrequency denervation after positive diagnostic block is documented in prospective and retrospective trials in patients suffering from upper limb CRPS. Lumbar sympathetic blocks can be performed with repeated local anesthetic injections. For a more prolonged lumbar sympathetic block radiofrequency treatment is preferred over phenol neurolysis because effects are comparable whereas the risk for side effects is lower (2 B+). For patients suffering from CRPS refractory to conventional treatment and sympathetic blocks, plexus brachialis block or continuous epidural infusion analgesia coupled with exercise therapy may be tried (2 C+). Spinal cord stimulation is recommended if other treatments fail to improve pain and dysfunction (2 B+). Alternatively peripheral nerve stimulation can be considered, preferentially in study conditions (2 C+).

Antinociceptive effect of linear polarized 0.6 to 1.6 um irradiation of lumbar sympathetic ganglia in chronic constriction injury rats

Linear polarized near-infrared light created with linear polarized near-infrared light therapy equipment (Super Lizer HA-550, Tokyo Iken Co, Ltd, Tokyo, Japan) has been used for the treatment of various painful disorders in Japan. Irradiation near the stellate ganglion with a Super Lizer (ISGL) is an especially notable therapeutic method used with stellate ganglion block (SGB) or substitutes for SGB. ISGL is a safe, simple, well-tolerated, and effective treatment. We examined the effects of irradiation with a Super Lizer applied to an area near the lumbar sympathetic ganglia on the ligated side in a chronic constriction injury (CCI) model, which is believed to be an animal model of complex regional pain syndrome (CRPS). Rats showing thermal hyperalgesia in a radiant heat test 1 wk postoperatively were used in Experiments 1 and 2: (1) Thermal hyperalgesia of irradiation group (n = 11) was less than that of the control or nonirradiation (n = 11) group at 1, 3, and 8 h after irradiation; however, the effect disappeared 12 h after irradiation. (2) Daily irradiation (n = 16) and 1 wk (n = 14) from 7 days after nerve ligation significantly shortened the interval from thermal hyperalgesia until recovery. Rats showing mechanical hyperalgesia in the von Frey hair test 1 wk postoperatively were used in Experiment 3: 1 wk irradiation beginning 7 days after nerve ligation (n = 9) did not promote the recovery from mechanical hyperalgesia. We speculate that repeated ISGL may be more effective than a single ISGL in alleviating pain in CRPS patients. We cannot explain the discrepancy between the results obtained in Experiments 2 and 3. We believe the results of this study are relevant to the effect of ISGL for patients with upper-limb CRPS: irradiation near the lumbar sympathetic ganglia of the rat is effective for thermal but not mechanical pain in CCI.

Evidence for cortical hyperexcitability of the affected limb representation area in CRPS: a psychophysical and transcranial magnetic stimulation study

Functional alterations in noxious, sensory and motor circuits within the central nervous system may play an important role in the pathophysiology of complex regional pain syndrome (CRPS). The aim of the present study was to search for further evidence of hyperexcitability in the hemisphere contralateral to the affected limb in patients with CRPS by employing both psychophysical and transcranial magnetic stimulation (TMS) methods. Twelve patients with CRPS type I, confined to the distal part of a limb (six in an upper-limb and six in a lower-limb), were enrolled in the study. The quantitative thermal, mechanical and ‘wind-up’ like pain testing was performed at the most painful site in the affected limb and in the ipsilateral limb. Results were then compared to those found at mirror sites in the contralateral limbs. TMS was used to assess the inter-hemispheric difference in parameters of corticospinal excitability, intracortical inhibition, and intracortical facilitation. The quantitative thermal and mechanical testing showed significant differences in cold, heat and mechanical pain thresholds, as well as in the first and last ‘wind-up’ stimuli between the affected and the contralateral limbs of the CRPS patients. No significant differences between the ipsilateral unaffected limbs and their contralateral pair limbs were found. A significant reduction in the short intracortical inhibition associated with a significant increase of the I-wave facilitation was found in the hemisphere contralateral to the affected side in the upper-limb CRPS group. No significant inter-hemispheric asymmetry between the affected and the non-affected sides was revealed in the lower-limb CRPS group. Taken together, these results suggest that in patients with well-localized CRPS, there is evidence for sensory and motor CNS hyperexcitability, though it seems to involve only corresponding regions within the CNS rather than the entire hemisphere.

Impairments and activity limitations in subjects with chronic upper-limb complex regional pain syndrome type I

Schasfoort FC, Bussmann JB, Stam HJ. Impairments and activity limitations in subjects with chronic upper-limb complex regional pain syndrome type I. Arch Phys Med Rehabil 2004;85:557–66. Objective To determine the degree of impairments and activity limitations and their interrelationship in complex regional pain syndrome type I (CRPS type I). Design Cross-sectional study interrelating impairments and objectively measured activity limitations. Setting Ambulatory and home environment. Participants Thirty nonacute upper-limb CRPS type I subjects. Interventions Not applicable. Main outcome measures Sensory, motor, and autonomic impairments, as well as activity-limitation outcome measures. The latter were objectively measured with a novel upper-limb activity monitor (based on ambulatory accelerometry). Results All subjects were impaired to some degree but with a large variability with respect to magnitude. Regarding activity limitations, the involved upper limb was clearly less active (lower intensity and percentage of activity) than the noninvolved side. Impaired active range of motion (adjusted R 2 range, 18%–39%) and grip strength (adjusted R 2 range, 12%–45%) were the most important factors explaining variance in activity limitations. Conclusions All subjects were still impaired nearly 3 years after the causative event. The involved upper limb was also clearly less active than the noninvolved side, especially when the subjects were sitting and when the dominant side was involved. The more impairments a subject had, especially motor impairments, the more activity limitations were present.