Shifting brain circuits in pain chronicity.

The evaluation of brain changes to a specific pain condition in pediatric and adult patients allows for insights into potential mechanisms of pain chronicity and possibly long-term brain changes. Here we focused on the primary somatosensory system (SS) involved in pain processing, namely the ventroposterolateral thalamus (VPL) and the primary somatosensory cortex (SI). We evaluated, using MRI, three specific processes: (a) somatotopy of changes in the SS for different pain origins (viz., foot vs. arm); (b) differences in acute (ankle sprain versus complex regional pain syndrome-CRPS); and (c) differences of the effects of CRPS on SS in pediatric versus adult patients. In all cases, age- and sex-matched individuals were used as controls. Our results suggest a shift in concurrent gray matter density (GMD) and resting functional connectivity strengths (rFC) across pediatric and adult CRPS with (a) differential patterns of GMD (VPL) and rFC (SI) on SS in pediatric vs. adult patterns that are consistent with upper and lower limb somatotopical organization; and (b) widespread GMD alterations in pediatric CRPS from sensory, emotional and descending modulatory processes to more confined sensory-emotional changes in adult CRPS and rFC patterns from sensory-sensory alterations in pediatric populations to a sensory-emotional change in adult populations. These results support the idea that pediatric and adult CRPS are differentially represented and may reflect underlying differences in pain chronification across age groups that may contribute to the well-known differences between child and adult pain vulnerability and resilience.

Bilaterally Reduced Intraepidermal Nerve Fiber Density in Unilateral CRPS-I.

Objective: Findings regarding small nerve fiber damage in complex regional pain syndrome type I (CRPS-I) are not uniform, and studies have not included a matched healthy control group. The aim was to assess intraepidermal nerve fiber density (IENFD) in relation to thermal sensitivity of the same skin areas in CRPS-I patients and a gender- and age-matched healthy control group. Methods: IENFD was investigated in skin biopsies from the CRPS-affected and contralateral limbs of eight CRPS-I patients and from an equivalent site in eight gender- and age-matched healthy controls (HCs). Thermal thresholds (cold/warm detection, cold- and heat-pain detection) were assessed on the affected limb, the matching contralateral limb, and on the equivalent limbs of HCs, and participants rated the intensity of cold/heat and pain to static thermal stimuli (5 °C and 40 °C). Results: IENFD was significantly lower in both the affected and contralateral limbs of CRPS-I patients than HCs, but IENFD did not differ between the affected and contralateral limbs of patients. The heat pain threshold was lower in the affected CRPS-I limb than in HCs, but all other thermal thresholds were similar in both groups. CRPS-I patients rated the cold stimulus as colder and more painful in the affected limb, and the warm stimulus as hotter, bilaterally, than the HCs. Conclusions: CRPS-I may be associated with bilateral small fiber damage, and perhaps small fiber neuropathy and bilateral disturbances in thermo-sensory perception. These disturbances could stem from a systemic response to injury or might increase the risk of developing CRPS-I after physical trauma.

Peripheral nerve pathology in patients with severely affected complex regional pain syndrome type I.

Complex regional pain syndrome type I (CRPS-I) is a chronic pain syndrome with no clinical evidence of nerve injury; however, recently, changes in muscle tissue have been found in case of CRPS-I. Our aim was to search for histological changes in peripheral nerves of amputated limbs from patients with therapy-resistant CRPS-I that could justify muscle tissue changes. Fifteen patients with CRPS-I (duration >1 year) were included. Multiple nerve samples were taken from upper (n=4) and lower (n=11) amputated limbs. Histological changes (signs of nerve fiber loss and regeneration), fiber diameters, fiber diameter distribution, and fiber density were studied through microscopy and morphometry. Samples from three healthy sural nerves were used as control data as well as data from the literature. All patients (93% of tissue samples) showed histological signs of nerve fiber loss and fiber regeneration, varying in severity. No specific preference was found for any nerve or the location within the nerve. Sural nerves showed loss of especially larger nerve fibers (>12 µm) in comparison with control data. Sympathectomy did not influence this finding. The morphometric results of the other nerves are more difficult to interpret because of the absence of good-quality control data from the literature. However, the percentages of nerve fibers greater than 12 µm seem to lie within the normal range. Besides the known pathology of thin nerve fibers innervating the skin or blood vessels in CRPS-I, this study also shows pathological changes more proximal in the nerves, especially in the sural nerve.

Microcirculatory changes identified by photoacoustic microscopy in patients with complex regional pain syndrome type I after stellate ganglion blocks.

Complex regional pain syndrome (CRPS) is a chronic pain syndrome that causes intractable pain, disability, and poor quality of life for patients. The etiology and pathophysiology of CRPS are still poorly understood. Due to a lack of proper diagnostic tools, the prognosis of CRPS is primarily based on clinical observation. The objective of this work is to evaluate a new imaging modality, photoacoustic microscopy (PAM), for assisting diagnoses and monitoring the progress and treatment outcome of CRPS. Blood vasculature and oxygen saturation (sO2) were imaged by PAM from eight adult patients with CRPS-1. Patients' hands and cuticles were imaged both before and after stellate ganglion block (SGB) for comparison. For all patients, both vascular structure and sO2 could be assessed by PAM. In addition, more vessels and stronger signals were observed after SGB. The results show that PAM can help diagnose and monitor CRPS.

Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

Evaluation of the structural quality of bone in a case of progressive osteoporosis complicating a Complex Regional Pain Syndrome (CRPS) of the upper limb.

Densitometry is considered to be the gold standard in bone quality assessment. However, since its introduction, the medical community has been aware that mineral density is only one of the factors that influence the bone risk of fracture, which also depends on the bone's trabecular arrangement and, in particular, on the trabecular architecture's load bearing capabilities. At the University of Trieste, in recent years, a test has been developed that simulates the application of compressive loads on trabecular architecture's reconstructions extracted from digital radiographs. In this work, the test is described, and the results obtained by applying the appraisal in a particular case of severe osteoporosis of the hand, complicating a Complex Regional Pain Syndrome (CRPS) type II, are presented. The test was able to quantify the pathological alterations of bone micro-architecture by means of a Structural Index (SI), which was absolutely significant and relevant to the clinical situation. Important research and clinical opportunities of application of the test include accurate evaluation of osteoporotic bone diseases, careful clinical follow-up and monitoring of responses to therapeutic approaches, and, prospectively, reliable quantification of biological damage (forensic field).

Morphological macrovascular alterations in complex regional pain syndrome type I demonstrated by increased intima-media thickness.

BACKGROUND: Although intima-media thickness (IMT) was increased in several inflammatory diseases, studies investigating whether the inflammatory processes lead to macrovascular alteration with increased IMT in complex regional pain syndrome (CRPS) lack. METHODS: Using ultrasound (high-resolution B-mode), we compared bilaterally the IMT of the common carotid artery (CCA-IMT), the radial artery (RA-IMT), the brachial artery (BRA-IMT) and the quotient QRA/CCA, in CRPS type I (n=17), peripheral nerve injury (PNI, n=17) and pain-free controls (PFC, n=22, matched to CRPS by gender, age and traditional cardiovascular risk factors). STATISTICS: Spearman's correlation, paired t-test, ANOVA (p<0.05). RESULTS: Compared to PFC, RA-IMT were significantly increased in both patient groups bilaterally (mean±standard deviation, CRPS affected side vs. PFC dominant side: 0.32±0.08 mm vs. 0.19±0.08 mm, p<0.001; PNI affected side vs. PFC dominant side: 0.27±0.09 mm vs. 0.19±0.08 mm, p< 0.05; CRPS non-affected side vs. PFC non-dominant side: 0.30±0.10 mm vs. 0.19±0.09 mm, p<0.001; PNI non-affected side vs. PFC non-dominant side: 0.25±0.10 mm vs. 0.19±0.09 mm, p<0.05) and QRA/CCA (CRPS affected-side vs. PFC dominant side: 0.49±0.12 vs. 0.30±0.11, p<0.001; PNI affected side vs. PFC dominant side: 0.41±0.10 vs. 0.30±0.11, p<0.05; CRPS non-affected side vs. PFC non-dominant side: 0.43±0.19 vs. 0.30±0.13, p<0.001; PNI non-affected side vs. PFC non-dominant side: 0.39±0.14 vs. 0.30±0.13, p<0.05), and BRA-IMT - only on the affected side in CRPS (CRPS: 0.42±0.06 mm vs. PFC: 0.35±0.08 mm; p<0.05). In CRPS, QRA/CCA was significantly higher on the affected side compared to PNI (p<0.05). However, only CRPS displayed within-group side-to-side differences with a significantly increased RA-IMT and QRA/CCA on the affected side (p<0.05). The CCA-IMT was comparable between all groups and sides. CONCLUSIONS: The increased IMT of peripheral arteries in CRPS suggests ongoing inflammatory process. Until now, only endothelial dysfunction has been reported. The presented morphological macrovascular alterations might explain the treatment resistance of some CRPS patients.

Skin biopsy in complex regional pain syndrome: case series and literature review.

BACKGROUND: Accumulating experimental and clinical evidence supports the hypothesis that complex regional pain syndrome type I (CRPS-I) may be a small fiber neuropathy. OBJECTIVES: To evaluate the use of commercially available standard biopsy methods to detect intradermal axon pathology in CRPS-I, and to ascertain if these structural changes can explain quantitative sensory testing (QST) findings in CRPS-I. STUDY DESIGN: Retrospective review of charts and laboratory data. SETTING: Outpatient clinic METHODS: Skin biopsies from 43 patients with CRPS-I were stained with PGP 9.5, and epidermal nerve fiber density, sweat gland nerve fiber density and morphological abnormalities were evaluated. Thirty-five patients had quantitative sensory testing. RESULTS: Alterations in skin innervation were seen in approximately 20% of CRPS-I patients with commercial processing. There were no patient characteristics, including duration of disease, that predicted a decreased epidermal nerve fiber density (ENFD). There was no consistent relationship between QST changes and ENFD measured by standard commercial skin biopsy evaluation procedures. LIMITATIONS: Commercial processing of tissue does not utilize stereologic quantitative analysis of nerve fiber density. Biopsy material is utilized from a proximal and distal source only, and differences in denervation of a partial nerve territory may be missed. The functional attributes of small fibers cannot be assessed. CONCLUSIONS: The negative results indicate that CRPS-I may be associated with changes in the ultramicroscopic small fiber structure that cannot be visualized with commercially available techniques. Alternatively, functional rather than structural alterations of small fibers or pathological changes at a more proximal site such as the spinal cord or brain may be responsible for the syndrome.

Modified graded motor imagery for complex regional pain syndrome type 1 of the upper extremity in the acute phase: a patient series.

Complex regional pain syndrome (CRPS) is a pathologic condition in which the painful experience is disproportionate in time and intensity in comparison with the inciting event. At present, the pathophysiology of CRPS is not well understood. Several studies have indicated that cortical reorganization plays a role in the persistence of the symptoms. A new promising approach, graded motor imagery (GMI), seems to be effective, but there are limited data for the CRPS-1 upper extremity population. The aim of this study was to demonstrate the effectiveness of a modified GMI (mGMI) protocol based on the work of Moseley to reduce pain and enhance functional capacities for a population with nonchronic CRPS-1 of the upper extremity. The following outcome measures were used to assess the clinical effectiveness: pain (short form of the McGill Pain Questionnaire), grip force (Martin vigorimeter), perception of upper extremity function (Disabilities of the Arm, Shoulder and Hand Questionnaire), and patient's global impression of change. All outcomes at T4 were compared with the baseline data (T0) using the Mann-Whitney test and the χ test (nonparametric tests). Seven patients were recruited for the study. At the end of the mGMI (T4), we obtained significant results for the decrease in the pain experienced in the last 7 days (visual analog scale; P=0.046), improvement in the affected extremity grip force (P=0.042), and the patient's global impression of change (P=0.015). However, the data of the perception of upper extremity function (Disabilities of the Arm, Shoulder and Hand Questionnaire) were not clinically or statistically significant. Our results indicate that this mGMI protocol seems to be a promising therapeutic modality to reduce pain. However, more investigations are needed to determine whether mGMI has a significant impact on upper extremity function.

The epidemiology of cervical spondylotic myelopathy.

OBJECTIVES: This is an observational study looking at the epidemiology of cervical spondylotic myelopathy of patients presenting to our hospital. MATERIALS AND METHODS: The notes and MRI scans of 41 patients presenting to the Leicester General Hospital with a clinical diagnosis of cervical myelopathy between January 2004 and December 2008 were reviewed retrospectively. RESULTS: Cervical myelopathy was found to be more common in male patients to the ratio of approximately 2.7:1, with an average age at diagnosis of 63.8 years. Multi-level disease was seen in the majority of patients, with C5/6 being the most commonly affected level. CONCLUSIONS: Cervical myelopathy predominantly affects men in their 7th decade of life. It is often a multi-level disease with C5/6 being the most commonly affected. It has little in common with cervical radiculopathy and is more analogous to lumber spinal stenosis.

Impaired oxygen utilization in skeletal muscle of CRPS I patients.

BACKGROUND: The purpose of this study was to evaluate oxygen extraction and utilization in end stage chronic complex regional pain syndrome type I (CRPS I) patients undergoing amputation and to relate these to muscle histology of the amputated limb. MATERIALS AND METHODS: In 25 patients with severe CRPS I requiring amputation of the affected limb venous blood samples and in 11 patients skeletal muscle specimens were analyzed. RESULTS: The mean venous oxygen saturation (S(v)O(2)) value (94.3% ± 4.0%) of the affected limb was significantly higher than S(v)O(2) values found in healthy subjects (77.5% ± 9.8%) pointing to a severely decreased oxygen diffusion or utilization within the affected limb. Histologic analysis showed a significant decrease of type I fibers and a significant increase of type IIB fibers. Ultrastructural investigations of soleus skeletal muscle capillaries revealed thickened endothelial cells and thickened basement membranes. Muscle capillary densities were decreased in comparison with literature data. High venous oxygen saturation levels were partially explained by impaired diffusion of oxygen due to thickened basement membrane and decreased capillary density. CONCLUSION: This study shows that venous oxygen saturation is significantly increased in chronic end stage CRPS I patients corresponding with impaired oxygen diffusion. The abnormal skeletal muscle findings points to severe disuse but only partially explain the impaired diffusion of oxygen; mitochondrial dysfunction seems a likely explanation in addition.

[The surgeon's viewpoint concerning Complex Regional Pain Syndrome 1]. / Le vécu de l'algoneurodystrophie ou syndrome douloureux régional complexe de type 1 par le chirurgien.

The complex regional pain syndrome type 1 from the surgeon's point of view: description of the symptoms, imaging (nuclear medicine, MRI) and of the associated psychological context. Importance of the need for a multi-disciplinary organization from the diagnostic to the therapeutic care.

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. A progressive-loading exercise program and management of pain-avoidance behavior without the use of specific medication ("pain exposure" physical therapy) is safe and effective for patients with complex regional pain syndrome.

The role of DTI in early detection of cervical spondylotic myelopathy: a preliminary study with 3-T MRI.

INTRODUCTION: The radiological diagnosis of cervical spondylotic myelopathy (CSM) has to be made as soon as possible, since surgery performed in earlier stages during the course of CSM was reported to be more successful when compared with later stages. We hypothesized that diffusion tensor imaging (DTI) may detect CSM in earlier stages, before the appearance of signal increase in T2-weighted sequences. METHODS: A total of 16 patients with neurological signs and symptoms of CSM but without hyperintensity in spinal cord on T2-weighted sequences enrolled in the study. The magnetic resonance (MR) examinations were performed on a 3-T MR imaging system. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were generated on axial plane. The ADC and FA measurements in each individual were made at the level of most severe cervical canal stenosis and at a nonstenotic level. Student's t test was used to compare FA and ADC values of the spinal cord in stenotic and nonstenotic segments. We also investigated if there was a correlation between DTI parametrics and duration of clinical symptoms by using Pearson correlation analysis. RESULTS: All patients showed changes in DTI parametrics at stenotic segments. While FA values of the spinal cord at the stenotic level showed a statistically significant reduction, there was a statistically significant increase in the measured ADC values (p < 0.001). There was no statistical correlation between the duration of symptoms and DTI parametrics. CONCLUSION: Our preliminary findings indicate that DTI may show abnormalities in the spinal cord before the development of T2 hyperintensity on conventional sequences in patients with CSM.

Changes with time in skin temperature of the shoulders in healthy controls and a patient with shoulder-hand syndrome.

BACKGROUND: Abnormal skin temperature in the shoulder is caused by various diseases. A thermography is unable to capture temperature changes over time. In contrast, a Thermocron is an effective measuring device to monitor temperature changes over time. PURPOSES: The purposes of this study employing a Thermocron were to measure shoulder skin temperature over time in healthy subjects and to detect shoulder skin temperature abnormalities in a patient with shoulder-hand syndrome. SUBJECTS AND METHODS: Subjects comprised 10 healthy volunteers (20 shoulders; 4 men and 6 women, mean age 54 years). For measurements, a Thermocron was attached on both shoulders. Measurements were made from 21.00 to 07.00 the following morning at 15-minute intervals. RESULTS: Gradual difference in right and left shoulder skin temperature was observed with the timing of measurements but no significant difference was apparent, i.e. dominant side 34.9 ± 0.8°C, non-dominant side 34.9 ± 0.9°C (P = 0.28). Presentation of a case with shoulder-hand syndrome. A 54-year-old woman with the diagnosis of rotator cuff tear underwent surgical treatment of rotator cuff repair, but the pain of the operated shoulder persisted due to phase 1 shoulder-hand syndrome. In postoperative week 3, skin temperature measurement using Thermocrons demonstrated a significant decrease in temperature on the operated side (affected side 34.3 ± 0.4°C, healthy side 35.2 ± 0.3°C; P < 0.05). CONCLUSION: The changing of the skin temperature during night-time was successfully recorded both in the healthy subjects and a case with shoulder-hand syndrome using a Thermocron.

Role of peripheral endothelin receptors in an animal model of complex regional pain syndrome type 1 (CRPS-I).

Chronic post-ischemic pain (CPIP) is an animal model of CRPS-I developed using a 3-h ischemia-reperfusion injury of the rodent hind paw. The contribution of local endothelin to nociception has been evaluated in CPIP mice by measuring sustained nociceptive behaviors (SNBs) following intraplantar injection of endothelin-1 or -2 (ET-1, ET-2). The effects of local BQ-123 (ETA-R antagonist), BQ-788 (ETB-R antagonist), IRL-1620 (ETB-R agonist) and naloxone (opioid antagonist) were assessed on ET-induced SNBs and/or mechanical and cold allodynia in CPIP mice. ETA-R and ETB-R expression was assessed using immunohistochemistry and Western blot analysis. Compared to shams, CPIP mice exhibited hypersensitivity to local ET-1 and ET-2. BQ-123 reduced ET-1- and ET-2-induced SNBs in both sham and CPIP animals, but not mechanical or cold allodynia. BQ-788 enhanced ET-1- and ET-2-induced SNBs in both sham and CPIP mice, and cold allodynia in CPIP mice. IRL-1620 displayed a non-opioid anti-nociceptive effect on ET-1- and ET-2-induced SNBs and mechanical allodynia in CPIP mice. The distribution of ETA-R and ETB-R was similar in plantar skin of sham and CPIP mice, but both receptors were over-expressed in plantar muscles of CPIP mice. This study shows that ETA-R and ETB-R have differing roles in nociception for sham and CPIP mice. CPIP mice exhibit more local endothelin-induced SNBs, develop a novel local ETB-R agonist-induced (non-opioid) analgesia, and exhibit over-expression of both receptors in plantar muscles, but not skin. The effectiveness of local ETB-R agonists as anti-allodynic treatments in CPIP mice holds promise for novel therapies in CRPS-I patients.

NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation.

A combination therapy of morphine with an NMDA-receptor antagonist might be more effective than morphine without a NMDA-receptor antagonist for the relief of neuropathic pain in patients with complex regional pain syndrome (CRPS). In order to test the efficacy of this combination therapy we performed a double-blind randomized placebo-controlled study on patients suffering from CRPS of the upper extremity. We used functional magnetic resonance imaging during movement of the affected and unaffected upper hand before and after a treatment regimen of 49 days that contrasted morphine and an NMDA-receptor antagonist with morphine and placebo. We postulated superior pain relief for the combination therapy and concomitant changes in brain areas associated with nociceptive processing. Only the combination therapy reduced pain at rest and during movement, and disability. After treatment, activation in the contralateral primary somatosensory (cS1) and anterior cingulate cortex was significantly reduced when the affected hand was moved. Pain relief during therapy was related to decreased activation in cS1 and secondary somatosensory cortex (S2). Our data suggest that the combination of morphine with an NMDA-receptor antagonist significantly affects the cerebral processing of nociceptive information in CRPS. The correlation of pain relief and decrease in cortical activity in cS1 and S2 is in accordance with the expected impact of the NMDA-receptor antagonist on cerebral pain processing with emphasis on sensory-discriminative aspects of pain.

Different activation of opercular and posterior cingulate cortex (PCC) in patients with complex regional pain syndrome (CRPS I) compared with healthy controls during perception of electrically induced pain: a functional MRI study.

OBJECTIVES: Although the etiology of complex regional pain syndrome type 1 (CRPS 1) is still debated, many arguments favor central maladaptive changes in pain processing as an important causative factor. METHODS: To look for the suspected alterations, 10 patients with CRPS affecting the left hand were explored with functional magnetic resonance imaging during graded electrical painful stimulation of both hands subsequently and compared with healthy participants. RESULTS: Activation of the anterior insula, posterior cingulate cortex (PCC), and caudate nucleus was seen in patients during painful stimulation. Compared with controls, CRPS patients had stronger activation of the PCC during painful stimulation of the symptomatic hand. The comparison of insular/opercular activation between controls and patients with CRPS I during painful stimulation showed stronger (posterior) opercular activation in controls than in patients. DISCUSSION: Stronger PCC activation during painful stimulation may be interpreted as a correlate of motor inhibition during painful stimuli different from controls. Also, the decreased opercular activation in CRPS patients shows less sensory-discriminative processing of painful stimuli.These results show that changed cerebral pain processing in CRPS patients is less sensory-discriminative but more motor inhibition during painful stimuli. These changes are not limited to the diseased side but show generalized alterations of cerebral pain processing in chronic pain patients.