A CRPS-IgG-transfer-trauma model reproducing inflammatory and positive sensory signs associated with complex regional pain syndrome

The aetiology of complex regional pain syndrome (CRPS), a highly painful, usually post-traumatic condition affecting the limbs, is unknown, but recent results have suggested an autoimmune contribution. To confirm a role for pathogenic autoantibodies, we established a passive-transfer trauma model. Prior to undergoing incision of hind limb plantar skin and muscle, mice were injected either with serum IgG obtained from chronic CRPS patients or matched healthy volunteers, or with saline. Unilateral hind limb plantar skin and muscle incision was performed to induce typical, mild tissue injury. Mechanical hyperalgesia, paw swelling, heat and cold sensitivity, weight-bearing ability, locomotor activity, motor coordination, paw temperature, and body weight were investigated for 8 days. After sacrifice, proinflammatory sensory neuropeptides and cytokines were measured in paw tissues. CRPS patient IgG treatment significantly increased hind limb mechanical hyperalgesia and oedema in the incised paw compared with IgG from healthy subjects or saline. Plantar incision induced a remarkable elevation of substance P immunoreactivity on day 8, which was significantly increased by CRPS-IgG. In this IgG-transfer-trauma model for CRPS, serum IgG from chronic CRPS patients induced clinical and laboratory features resembling the human disease. These results support the hypothesis that autoantibodies may contribute to the pathophysiology of CRPS, and that autoantibody-removing therapies may be effective treatments for long-standing CRPS.     

Health-related quality of life in 975 patients with complex regional pain syndrome type 1

There are limited data available on health-related quality of life (QoL) in patients with complex regional pain syndrome (CRPS). In the present study we examined QoL in 975 CRPS patients attending 6 different clinics in the Netherlands. QoL was assessed using the MOS 36-Item Short-Form Health Survey (SF-36) with the Mental Health Summary Score (MHS) and the Physical Health Summary Score (PHS) as dependent variables. The influences of gender, type of affected limb, disease duration, pain scores, CRPS severity and set of diagnostic criteria used were investigated. We found the lowest scores of QoL in the physical domains of the SF-36, with lower-limb CRPS patients reporting poorer results than patients with an affected upper limb. Influence of gender on QoL was not observed, and correlations of QoL with disease duration and the CRPS severity score were weak. Pain correlated moderately with QoL. In addition, patients fulfilling stricter diagnostic criteria (ie, the Budapest criteria) had lower QoL scores than patients fulfilling less strict criteria (ie, the Orlando criteria). We conclude that loss of QoL in CRPS patients is due mainly to reduced physical health. A comparison with data available from the literature shows that CRPS patients generally report poorer QoL than patients with other chronic pain conditions, particularly in the physical domains. Pain correlated moderately with QoL and therefore deserves ongoing attention by physicians. Finally, patients meeting the diagnostic Budapest criteria have lower QoL scores than patients meeting the Orlando criteria, highlighting the impact of different sets of criteria on population characteristics.     

A case of complex regional pain syndrome with agnosia for object orientation

This systematic investigation of the neurocognitive correlates of complex regional pain syndrome (CRPS) in a single case also reports agnosia for object orientation in the context of persistent CRPS. We report a patient (JW) with severe long-standing CRPS who had no difficulty identifying and naming line drawings of objects presented in 1 of 4 cardinal orientations. In contrast, he was extremely poor at reorienting these objects into the correct upright orientation and in judging whether an object was upright or not. Moreover, JW made orientation errors when copying drawings of objects, and he also showed features of mirror reversal in writing single words and reading single letters. The findings are discussed in relation to accounts of visual processing. Agnosia for object orientation is the term for impaired knowledge of an object’s orientation despite good recognition and naming of the same misoriented object. This defect has previously only been reported in patients with major structural brain lesions. The neuroanatomical correlates are discussed. The patient had no structural brain lesion, raising the possibility that nonstructural reorganisation of cortical networks may be responsible for his deficits. Other patients with CRPS may have related neurocognitive defects.     

Cognitive correlates of "neglect-like syndrome" in patients with complex regional pain syndrome

Patients with complex regional pain syndrome (CRPS) often show distinct neurocognitive dysfunctions, which were initially termed "neglect-like symptoms." So far, particularly the patients' feelings about the affected extremity, motor, and sensory aspects of the "neglect-like symptoms" have been investigated, possibly pointing to a disturbed body schema. Because patients with classical neurological neglect show diminished awareness regarding the perception of their body, as well as of the space around them, our hypothesis was that CRPS patients exhibit some signs of personal neglect and extrapersonal visuospatial problems over and beyond those seen in patients simply suffering from limb pain. We used quantitative sensory testing and motor assessment aimed at detecting motor and sensory loss, a standardized questionnaire calculating a neglect score, and applied a detailed neuropsychological test battery assessing different parietal lobe functions, including visual neglect. We examined 20 CRPS patients and 2 matched control groups, one consisting of healthy subjects and the other one of patients with limb pain other than CRPS. Results show significant higher neglect scores for CRPS patients and the pain control group, but interestingly, CRPS patients and pain patients were indistinguishable. The results of the neuropsychological test battery did not demonstrate systematic variances, which would be indicative of a classical neurological neglect in CRPS patients, even though there were 3 CRPS patients who differed ≥ 2 SD from the mean of our healthy control group, with poorer results in ≥ 3 different tests. We assume that the "neglect-like syndrome" in most CRPS patients is different from typical neglect.     

Muscle hyperalgesia is widespread in patients with complex regional pain syndrome

Patients with complex regional pain syndrome (CRPS) frequently show prominent sensory abnormalities in their affected limb, which may extend proximally and even to unaffected body regions. This study examines whether sensory dysfunction is observed in unaffected body parts of CRPS patients, and investigates whether the extent of dysfunction is similar for the various sensory modalities. Quantitative sensory testing was performed in the unaffected extremities and cheeks of 48 patients with CRPS of the arm (31 with dystonia), and the results were compared with values obtained among healthy controls. The most prominent abnormality was the pressure pain threshold, which showed a consistent pattern of higher sensitivity in unaffected contralateral arms and unaffected legs, as well as the cheek, and demonstrated the largest effect sizes. The cheeks of CRPS patients showed thermal hypoesthesia and hyperalgesia as well as a loss of vibration detection. Except for a lower vibration threshold in the contralateral leg of CRPS patients with dystonia, no differences in sensory modalities were found between CRPS patients with and without dystonia. These results point to a general disturbance in central pain processing in patients with CRPS, which may be attributed to impaired endogenous pain control. Since pressure pain is the most deviant sensory abnormality in both unaffected and affected body regions of CRPS patients, this test may serve as an important outcome parameter in future studies and may be used as a tool to monitor the course of the disease.     

Autoimmunity contributes to nociceptive sensitization in a mouse model of complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a painful, disabling, chronic condition whose etiology remains poorly understood. The recent suggestion that immunological mechanisms may underlie CRPS provides an entirely novel framework in which to study the condition and consider new approaches to treatment. Using a murine fracture/cast model of CRPS, we studied the effects of B-cell depletion using anti-CD20 antibodies or by performing experiments in genetically B-cell-deficient (μMT) mice. We observed that mice treated with anti-CD20 developed attenuated vascular and nociceptive CRPS-like changes after tibial fracture and 3 weeks of cast immobilization. In mice with established CRPS-like changes, the depletion of CD-20+ cells slowly reversed nociceptive sensitization. Correspondingly, μMT mice, deficient in producing immunoglobulin M (IgM), failed to fully develop CRPS-like changes after fracture and casting. Depletion of CD20+ cells had no detectable effects on nociceptive sensitization in a model of postoperative incisional pain, however. Immunohistochemical experiments showed that CD20+ cells accumulate near the healing fracture but few such cells collect in skin or sciatic nerves. On the other hand, IgM-containing immune complexes were deposited in skin and sciatic nerve after fracture in wild-type, but not in μMT fracture/cast, mice. Additional experiments demonstrated that complement system activation and deposition of membrane attack complexes were partially blocked by anti-CD20+ treatment. Collectively, our results suggest that CD20-positive B cells produce antibodies that ultimately support the CRPS-like changes in the murine fracture/cast model. Therapies directed at reducing B-cell activity may be of use in treating patients with CRPS.     

Autoantibodies in complex regional pain syndrome bind to a differentiation-dependent neuronal surface autoantigen

Complex regional pain syndrome, which is characterised by pain and trophic disturbances, develops frequently after peripheral limb trauma. There is an increasing evidence of an involvement of the immune system in CRPS, and recently we showed that CRPS patients have autoantibodies against nervous system structures [6]. Therefore we tested the sera of CRPS patients, neuropathy patients and healthy volunteers for surface-binding autoantibodies to primary cultures of autonomic neurons and differentiated neuroblastoma cell lines using flow cytometry. Thirteen of 30 CRPS patients, but none of 30 healthy controls and only one of the 20 neuropathy sera had specific surface binding to autonomic neurons (p < 0.001). The majority of the sera reacted with both sympathetic and myenteric plexus neurons. Interestingly, 6/30 CRPS sera showed binding to undifferentiated SH-SY5Y neuroblastoma cells. However, differentiation of SH-SY5Y into a cholinergic phenotype induced a surface antigen, which is recognised by 60% of CRPS sera (18/30), but not by controls (p < 0.001). Our data show that about 30–40% of CRPS patients have surface-binding autoantibodies against an inducible autonomic nervous system autoantigen. These data support an autoimmune hypothesis in CRPS patients. Further studies must elucidate origin and function of these autoantibodies in CRPS.     

Safety of "pain exposure" physical therapy in patients with complex regional pain syndrome type 1

“Pain exposure” physical therapy (PEPT) is a new treatment for patients with complex regional pain syndrome type 1 (CRPS-1) that consists of a progressive-loading exercise program and management of pain-avoidance behavior without the use of specific CRPS-1 medication or analgesics. The aim of this study was to investigate primarily whether PEPT could be applied safely in patients with CRPS-1. Twenty patients with CRPS-1 were consecutively enrolled in the study after giving informed consent. The diagnosis of CRPS-1 was defined using the Bruehl and Harden/IASP diagnostic criteria. CRPS-1 was diagnosed between 3 and 18 months after the inciting event (trauma). According to a multiple single-case design (baseline [A1], treatment [B], follow-up [A2]), multiple baseline and follow-up measurements were performed to evaluate changes in CRPS signs and symptoms and to assess functional parameters. When comparing the baseline with the follow-up phase, patients improved significantly with respect to pain on the visual analogue scale (57%), pain intensity (48%), muscle strength (52%), arm/shoulder/hand disability (36%), 10-meter walking speed (29%), pain disability index (60%), kinesiophobia (18%), and the domains of perceived health change in the SF-36 survey (269%). Three patients initially showed increased vegetative signs but improved in all other CRPS parameters and showed good functional recovery at follow-up. We conclude that PEPT is a safe and effective treatment for patients with CRPS-1.     

Demographic and medical parameters in the development of complex regional pain syndrome type 1 (CRPS1): prospective study on 596 patients with a fracture

Limited data are available on the incidence of complex regional pain syndrome type 1 (CRPS1) and on demographic and medical risk factors for the development of CRPS1. The objective of this study was to investigate the incidence of CRPS1 in patients with a fracture using 3 sets of diagnostic criteria and to evaluate the association between demographic/medical factors and the development of CRPS1 diagnosed with the Harden and Bruehl criteria. A prospective multicenter cohort study of 596 patients (ages 18 years and older) with a single fracture of the wrist, scaphoid, ankle, or metatarsal V, recruited patients from the emergency rooms of 3 Dutch hospitals. Of the 596 participants, 42 (7.0%) were diagnosed with CRPS1 according to the Harden and Bruehl criteria, 289 (48.5%) according to the International Association for the Study of Pain criteria, and 127 (21.3%) according to the criteria of Veldman. An analysis of the medical and demographic differences revealed that patients in whom CRPS1 later developed more often had intra-articular fractures, fracture dislocations, rheumatoid arthritis, or musculoskeletal comorbidities. An ankle fracture, dislocation, and an intra-articular fracture contributed significantly to the prediction of the development of CRPS1. No CRPS1 patients were symptom free at 12 months (T3). At baseline, patients with CRPS1 had significantly more pain than patients without CRPS1 (P<.001). The incidence of the diagnosis of CRPS1 after a single fracture depends to a large extent on the diagnostic criteria used. After a fracture, 7% of the patients developed CRPS1 and none of the patients were free of symptoms at 1-year follow-up.     

Comparison of muscle and joint pressure-pain thresholds in patients with complex regional pain syndrome and upper limb pain of other origin

Pain localized in the deep tissues occurs frequently in complex regional pain syndrome (CRPS). In addition, hyperalgesia to blunt pressure over muscles is common in CRPS, but it often appears in limb pain of other origin as well. Considering that 3-phase bone scintigraphy (TPBS) reveals periarticular enhanced bone metabolism in CRPS, joint-associated hyperalgesia to blunt pressure might be a more specific finding than hyperalgesia over muscles. In 34 patients with upper limb pain (18 CRPS, 16 non-CRPS; diagnosed in accordance to the Budapest criteria) and in 18 healthy controls, pressure-pain thresholds (PPT) were assessed bilaterally over the thenar (PPT_Thenar), the metacarpophalangeal (PPT_MCP), and the proximal interphalangeal (PPT_PIP) joints using a pressure algometer (Somedic, Sweden). Beforehand, all patients had received TPBS for diagnostic purposes independently of the study. Region-of-interest (ROI) ratios (mineralization phase) for the MCP and PIP, excluding fracture sites, were correlated with the PPT. In CRPS, all ROI ratios were significantly increased and all PPT of the affected hand were decreased compared to non-CRPS (PPT_Thenar: 243 ± 150 kPa vs 358 ± 197 kPa, PPT_MCP: 80 ± 67 kPa vs 159 ± 93 kPa, PPT_PIP: 80 ± 56 kPa vs 184 ± 110 kPa; P < .01) and controls (PPT_Thenar: 478 ± 106 kPa, PPT_MCP: 254 ± 50 kPa, PPT_PIP: 275 ± 76 kPa; P < .01). A PPT_Thenar below 293 kPa revealed 77% sensitivity but only 63% specificity, whereas a PPT_PIP below 102 kPa had 82% sensitivity and 94% specificity to identify CRPS. Only in CRPS were PPT_MCP and PPT_PIP correlated significantly inversely with the ROI ratio (MCP: r = −0.439, PIP: r = −0.447). PPT_PIP shows higher specificity for CRPS type I than PPT_Thenar without loss of sensitivity. Therefore, measurement of joint PPT could be a noninvasive diagnostic tool reflecting increased bone metabolism assessed by TPBS as a sign of bone pathophysiology.     

Familial occurrence of complex regional pain syndrome

Genetic factors are suggested to play a role in complex regional pain syndrome (CRPS), but familial occurrence has not been extensively studied. In the present study we evaluated familial occurrence in Dutch patients with CRPS. Families were recruited through the Dutch Association of CRPS patients and through referral by clinicians. The number of affected members per family, the phenotypic expression and inheritance were assessed. Demographic and clinical characteristics of familial CRPS (fCRPS) patients were compared with those of sporadic CRPS (sCRPS) patients from a Dutch population‐based study and with a group of sCRPS patients that was proportionally matched for referral center of the fCRPS probandi to control for referral bias. Thirty‐one CRPS families with two or more affected relatives were identified, including two families with five, four with four, eight with three and 17 with two affected relatives. In comparison with sCRPS patients, fCRPS patients had a younger age at onset and more often had multiple affected extremities and dystonia. We conclude that CRPS may occur in a familial form, but did not find a clear inheritance pattern. Patients with fCRPS develop the disease at a younger age and have a more severe phenotype than sporadic cases, suggesting a genetic predisposition to develop CRPS.     

Intrathecal glycine for pain and dystonia in complex regional pain syndrome

Since glycinergic neurotransmission plays an important inhibitory role in the processing of sensory and motor information, intrathecal glycine (ITG) administration may be a potential therapy for both pain and movement disorders in patients with complex regional pain syndrome (CRPS). Aims of the current study, which is the first report on ITG in humans, were to evaluate its safety and efficacy. ITG treatment during 4 weeks was studied in CRPS patients with dystonia in the period before they received intrathecal baclofen treatment. Twenty patients were assessed and after exclusion of one patient, the remaining 19 patients were randomized in a double-blind placebo-controlled crossover study. Safety was assessed by clinical evaluation, blood examinations and electrocardiograms. Efficacy measures involved pain (numeric rating scale, McGill pain questionnaire), movement disorders (Burke–Fahn–Marsden dystonia rating scale, unified myoclonus rating scale, tremor research group rating scale), activity (Radboud skills questionnaire, walking ability questionnaire), and a clinical global impression (CGI) and patient’s global impression score (PGI). Treatment-emergent adverse events were generally mild to moderate and not different from placebo treatment. During ITG treatment growth hormone levels were slightly increased. Although there was a trend to worsening on the CGI and PGI during ITG treatment, there were no significant differences between ITG and placebo treatment in any of the outcomes. ITG given over 4 weeks was ineffective for pain or dystonia in CRPS. Although no serious adverse events occurred, further studies are required to rule out potential neurotoxicity of ITG.     

Proximal myofascial pain in patients with distal complex regional pain syndrome of the upper limb

BackgroundPatients suffering from complex regional pain syndrome (CRPS) endure myofascial-related pain in at least 50% of cases.AimsTo evaluate the association of upper limb CRPS with myofascial pain in muscles that might influence arm or hand pain, and to evaluate whether the paraspinal skin and subcutaneous layers’ tenderness and allodynia are associated with CRPS.MethodsA case-control study comprising 20 patients presenting with upper limb CRPS, and 20 healthy controls matched for sex and age, were evaluated in the thoracic paraspinal area and myofascial trigger points (MTrPs) (infraspinatus, rhomboids, subclavius, serratus posterior superior and pectoralis minor) via a skin rolling test.ResultsThe prevalence of MTrPs in the affected extremity of the subjects was significantly higher than in the right limb of the controls: 45% exhibited active and latent MTrPs in the infraspinatus muscle (χ² = 11.613, p = 0.001); 60% in active and latent MTrPs in the subclavius muscle (χ² = 17.143, p < 0.001); and in the pectoralis minor muscle (χ2 = 13.786, p < 0.001). In addition, 55% of the cases exhibited active and latent MTrPs in the serratus posterior superior muscle (χ² = 15.172, p < 0.001). Significant differences between the groups in skin texture and pain levels (p = 0.01, p < 0.001, respectively) demonstrated that CRPS patients felt more pain, and their skin and subcutaneous layers were much tighter than in the healthy controls.ConclusionThere is a high prevalence of MTrPs in the shoulder and upper thoracic area muscles in subjects who suffer from CRPS. We recommend adding an MTrPs evaluation to the standardized examination of these patients.     

The association between psychological factors and the development of complex regional pain syndrome type 1 (CRPS1) — A prospective multicenter study

The objective of this study was to investigate the association between psychological factors and complex regional pain syndrome type 1 (CRPS1). A prospective multicenter cohort study was performed involving the emergency room of three hospitals, and patients age 18 years or older, with a single fracture, were included in the study. At baseline (T0), participants completed a questionnaire covering demographic, psychological (Symptom Checklist‐90), and medical variables. At plaster removal (T1) and at T2, the participants completed a questionnaire addressing symptoms of CRPS1. Psychological factors that were analysed were agoraphobia, depression, somatization, insufficiency, (interpersonal) sensitivity, insomnia, and life events. In total, 596 consecutive patients were included in the study, and 7.0% were diagnosed with CRPS1. None of the psychological factors predicted the development of CRPS1. The scores on the Symptom Checklist‐90 subscales fell into the range of the general population and were, in most cases, average or below average when compared with those of pain patients or psychiatric patients. No empirical evidence supports a diagnosis of CRPS1 patients as psychologically different, and the current results indicate that there is no association between psychological factors and CRPS1.     

Spinal cord stimulation in adolescents with complex regional pain syndrome type I (CRPS‐I)

Complex regional pain syndrome type I (CRPS‐I) is not uncommon in children, particularly in adolescent girls. Most often, the condition involves a foot and is characterized by spontaneous pain, tactile allodynia and dysautonomic signs. There is usually a history of a minor, local trauma but sometimes no reasonable cause can be identified, and there are no signs of persistent tissue injury giving rise to ongoing nociception. Common analgesics are generally of no benefit, and the standard treatment includes sociopsychological support, physiotherapy, tricyclic antidepressants and antiepileptic drugs, sympathetic blocks (SB), and cognitive‐behavioural therapy. For a minority of patients who prove to be resistant to such therapies, spinal cord stimulation (SCS) may be tried. The present study comprises seven girls, 11–14 years of age, presenting with severe, incapacitating and therapy‐resistant CRPS‐I, who were subjected to SCS. In two of them, percutaneous electrode implantation had to be performed in general anaesthesia. Trial stimulation was performed in all, but one. In two cases, it was not possible to produce paraesthesias that entirely covered the pain area. A pain relieving effect of SCS was usually not reported until after 1–2 weeks of trial stimulation. After another 2–6 weeks, pain alleviation was complete in five of the seven patients, one to eight years after the intervention. In one case, a local infection necessitated the removal of the electrode; nevertheless a few days of trial stimulation produced substantial pain relief that still persists. In four patients, the SCS use was gradually diminished and eventually the device could be removed. The favourable outcome in all seven cases with no or minor remaining symptoms and without severe recurrences illustrates that SCS may also be an efficient treatment in paediatric cases with exceptionally therapy resistant forms of CRPS I.     

Impaired self-perception of the hand in complex regional pain syndrome (CRPS)

To investigate neglect, extinction, and body-perception in patients suffering from complex regional pain syndrome (CRPS). So-called ‘neglect-like’ symptoms have been reported in CRPS, however no studies have yet analyzed this phenomenon which might substantiate the theory of the central nervous system involvement in the pathophysiology of CRPS. A total of 114 patients with CRPS of the upper limb underwent bedside neurological examination. ‘Neglect-like’ symptoms were determined by asking all patients what kind of feeling they had toward the affected hand (feeling of foreignness). Hemispatial neglect was tested with the line bisection task in 29 patients and sensory extinction to simultaneous stimulation in 40 patients. The ability to identify fingers after tactile stimulation was tested in 73 patients. Independently of the affected side and disease duration, 54.4% of the patients reported that their hand felt ‘foreign’ or ‘strange’. The ability to identify fingers was impaired in 48% on the affected hand and in 6.5% on the unaffected hand (X²=33.52, df=1, p<0.0001). These findings were related to pain intensity, illness duration and the extent of sensory deficits. No typical abnormalities indicating neglect were found in the line bisection test. Sensory extinction was normal in all patients. A large proportion of CRPS patients have disturbances of the self-perception of the hand, indicating an alteration of higher central nervous system processing. There are no indicators that classic neglect or extinction contribute to these findings. Physical therapy of such patients should take this observation into consideration.     

Epidermal adrenergic signaling contributes to inflammation and pain sensitization in a rat model of complex regional pain syndrome

In many patients, the sympathetic nervous system supports pain and other features of complex regional pain syndrome (CRPS). Accumulating evidence suggests that interleukin (IL)-6 also plays a role in CRPS, and that catecholamines stimulate production of IL-6 in several tissues. We hypothesized that norepinephrine acting through specific adrenergic receptors expressed on keratinocytes stimulates the production of IL-6 and leads to nociceptive sensitization in a rat tibial fracture/cast model of CRPS. Our approach involved catecholamine depletion using 6-hydroxydopamine or, alternatively, guanethidine, to explore sympathetic contributions. Both agents substantially reduced nociceptive sensitization and selectively reduced the production of IL-6 in skin. Antagonism of IL-6 signaling using TB-2-081 also reduced sensitization in this model. Experiments using a rat keratinocyte cell line demonstrated relatively high levels of β2-adrenergic receptor (β2-AR) expression. Stimulation of this receptor greatly enhanced IL-6 expression when compared to the expression of IL-1β, tumor necrosis factor (TNF)-α, or nerve growth factor. Stimulation of the cells also promoted phosphorylation of the mitogen-activated protein kinases P38, extracellular signal-regulated kinase, and c-Jun amino-terminal kinase. Based on these in vitro results, we returned to animal testing and observed that the selective β2-AR antagonist butoxamine reduced nociceptive sensitization in the CRPS model, and that local injection of the selective β2-AR agonist terbutaline resulted in mechanical allodynia and the production of IL-6 in the cells of the skin. No increases in IL-1β, TNF-α, or nerve growth factor levels were seen, however. These data suggest that in CRPS, norepinephrine released from sympathetic nerve terminals stimulates β2-ARs expressed on epidermal keratinocytes, resulting in local IL-6 production, and ultimately, pain sensitization.     

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.     

Cerebral activation during motor imagery in complex regional pain syndrome type 1 with dystonia

The pathogenesis of dystonia in Complex Regional Pain Syndrome type 1 (CRPS-1) is unclear. In primary dystonia, functional magnetic resonance imaging (fMRI) has revealed changes in cerebral networks during execution of movement. The aim of this study was to determine cerebral network function in CRPS-1 patients with dystonic postures. Cerebral processing related to both execution and imagining of hand movements in patients and controls was assessed with fMRI. Eight CRPS-1 patients with dystonic postures of the right upper extremity and 17 age-matched healthy controls were studied. Compared with controls, imaginary movement of the affected hand in patients showed reduced activation ipsilaterally in the premotor and adjacent prefrontal cortex, and in a cluster comprising frontal operculum, the anterior part of the insular cortex and the superior temporal gyrus. Contralaterally, reduced activation was seen in the inferior parietal and adjacent primary sensory cortex. There were no differences between patients and controls when they executed movements, nor when they imagined moving their unaffected hand. The altered cerebral activation pattern in patients with CRPS-1 linked dystonia most likely reflects an interface between pain-associated circuitry and higher order motor control, which points at a specific mechanistic pathophysiology of this type of dystonia.     

Multimodal physical therapy management of a 48-year-old female with post-stroke complex regional pain syndrome

Abstract

This case report describes a 48-year-old female who presented with complaints of right shoulder pain, hyperesthesias and swelling of the hand along with added symptoms of pain centralization following a cerebrovascular accident. On clinical evaluation, the patient satisfied the Budapest diagnostic criteria for Complex Regional Pain Syndrome (CRPS) type-1. Physical therapy management (1st three sessions) was initially focused on pain neurophysiology education with an aim to reduce kinesiophobia and reconceptualise her pain perception. The patient had an immediate significant improvement in her pain and functional status. Following this, pain modulation in the form of transcutaneous electrical nerve stimulation, kinesio tape application, “pain exposure” physical therapy and exercise therapy was carried out for a period of 7 weeks. The patient had complete resolution of her symptoms which was maintained at a six-month follow-up.