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Objective: To investigate the effects of mirror therapy applied in addition to routine rehabilitation on clinical outcomes in post-traumatic complex regional pain syndrome type 1., Design: Single-blind randomized controlled trial., Subjects: Patients with trauma-induced complex regional pain syndrome type 1 of the hand receiving outpatient rehabilitation., Methods: Patients were randomized into mirror therapy and control groups. All patients received routine physical therapy and rehabilitation for 20 sessions (5 sessions/week, for 4 weeks). The mirror group received additional mirror therapy at each session. The primary outcome was pain intensity by numeric rating scale. Secondary outcomes were grip/pinch strength, hand/wrist circumference, dexterity, hand activities, and health-related quality of life. All assessments were performed before and immediately after the treatment, and 4 weeks later at follow-up., Results: Forty patients were enrolled, 20 in each group. Both groups revealed statistically significant improvements from therapy regarding pain, grip/pinch strength, wrist circumference, dexterity, and hand activities (p <  0.05). When groups were compared regarding the improvements in assessment parameters, no statistically significant difference was found between the 2 groups in any of the outcomes (p > 0.05)., Conclusion: Mirror therapy applied in addition to routine therapy in post-traumatic complex regional pain syndrome type 1 did not provide extra benefit to the improvement of pain, function, and other clinical outcomes.

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., (© 2019 Wiley Periodicals, Inc.)

Background: Complex regional pain syndrome (CRPS) can be a devastating complication following extremity injury, but risk factors are not well understood. The purpose of this study was to investigate the association between fibromyalgia and the development of CRPS after distal radius fracture. Methods: The PearlDiver Medicare database was queried using International Classification of Diseases, 9th Revision (ICD-9) and Current Procedural Terminology (CPT) codes for diagnoses and treatments of distal radius fractures. Patients were separated into fibromyalgia and control cohorts, and the prevalence of CRPS was measured at 3, 6, 9, and 12 months from the date of injury or procedure. Demographic factors, treatment modality, and comorbid conditions were analyzed by multivariable logistic regression to reduce confounding and identify additional risk factors. Results: Database queries yielded 853 186 patients diagnosed or treated for distal radius fracture, with 6% having previous diagnosis of fibromyalgia. The prevalence of CRPS following distal radius fracture was increased at 3, 6, 9, and 12 months in the fibromyalgia cohort compared with the control c, with a 1-year incidence of 0.51% compared with 0.20% (odds ratio [OR], 2.54, P < .001). Multivariable logistic regression supported the association, with estimated OR of 2.0 ( P < .001). In addition, female gender, surgical or manipulative treatment, and anxiety were positively associated with CRPS, and age >65, diabetes, and heart failure were negatively associated. Conclusions: While the basis of the association between fibromyalgia and CRPS is unknown, our data suggest that it could serve as a useful predictor of CRPS risk, promoting increased vigilance for CRPS symptoms and earlier recognition and treatment, thereby improving patient outcomes.

This study aimed to evaluate the incidence rates of and risk factors for complex regional pain syndrome type 1 (CRPS-1) after surgery for distal radius fractures (DRFs). Using data from January 2007 to December 2014, we analysed the data from the Korean Health Insurance Review and Assessment (HIRA) service. After extracting the data of patients aged ≥18 years whose diagnostic and operation codes for DRFs were entered into the HIRA database, we analysed the incidence rates of and risk factors for CRPS-1. From 2007 to 2014, 172,194 DRFs were treated surgically. Within 1 year postoperatively, 1,103 CRPS-1 cases were diagnosed, with an incidence of 0.64%. On univariate and multivariate analyses, the risk factors that significantly correlated with the incidence of CRPS-1 included female sex, rheumatoid arthritis, open reduction, open fracture, and accompanying ulnar fracture, whereas old age, psychiatric disease, and external fixation were not statistically significant. The incidence of CRPS-1 after surgery for DRF was very low (0.64%) in South Korea. Careful monitoring is necessary for patients with complex fractures and rheumatoid arthritis who are at increased risk of developing CRPS-1.

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.

Neuropathic pain in a chronic post-ischaemic pain (CPIP) model mimics the symptoms of complex regional pain syndrome type I (CRPS I). The administration of bee venom (BV) has been utilized in Eastern medicine to treat chronic inflammatory diseases accompanying pain. However, the analgesic effect of BV in a CPIP model remains unknown. The application of a tight-fitting O-ring around the left ankle for a period of 3 h generated CPIP in C57/Bl6 male adult mice. BV (1 mg/kg ; 1, 2, and 3 times) was administered into the SC layer of the hind paw, and the antiallodynic effects were investigated using the von Frey test and by measuring the expression of neurokinin type 1 (NK-1) receptors in dorsal root ganglia (DRG). The administration of BV dose-dependently reduced the pain withdrawal threshold to mechanical stimuli compared with the pre-administration value and with that of the control group. After the development of the CPIP model, the expression of NK-1 receptors in DRG increased and then decreased following the administration of BV. SC administration of BV results in the attenuation of allodynia in a mouse model of CPIP. The antiallodynic effect was objectively proven through a reduction in the increased expression of NK-1 receptors in DRG.

Objectives: Spinal cord stimulation (SCS) is used for various indications such as Failed Back Surgey Syndrome, peripheral causalgia, neuropathic pain, complex regional pain syndrome, reflex sympathetic dystrophy, peripheral vascular disease, ischemic heart disease and cancer pain., Methods: This is a retrospective study. 62 patients applied SCS were included in retrospective study from february 2011-january 2015 in Akdeniz University medicine faculty algology department. We asked about patients' VAS values before and after procedure, analgesic medicine usings, sleep disorders, pleasure after procedure, daily activity improvement and time of going back to work., Results: We found that decrease on the patients' pain severity and improvement on quality of sleep and daily activities., Conclusion: As a result; our study and the other studies show that SCS is reliable and effective procedure on chronic pain management.

According to the International Association for the Study of Pain (IASP) and American Medical Association (AMA), the diagnostic criteria for complex regional pain syndrome (CRPS) require the presence of skin temperature asymmetry. In CRPS, it is generally accepted that the temperature of skin of affected limbs changes from warm to cold; however, in our clinical practice, we have experienced many cases with different thermographic characteristics. Therefore, we conducted a retrospective multicenter study that examined the distribution of skin temperature in patients with CRPS and skin temperature asymmetry versus symptom duration.Patients diagnosed with type 1 or 2 CRPS were recruited. After confirming CRPS according to the IASP diagnostic criteria, infrared thermographic images were evaluated for skin temperature differences (ΔT) between the affected and unaffected limbs.A total of 296 patients with CRPS were included in this study. The median duration of symptoms was 6 months and the mean ± standard deviation of ΔT was -0.72 ± 1.65°C. A skin temperature difference between bilateral limbs (|ΔT|) of 1°C or less was seen in 131 patients (44.3%); thus, these 131 patients did not meet the IASP criteria for CRPS. Further, cool skin temperature was not observed in 88 patients (29.7%), meaning that these patients did not meet the AMA criteria for CRPS. There was no correlation between the symptom duration and ΔT (Spearman's rho = -0.075, P = 0.196) and there was no significant difference in the average ΔT among the 4 symptom duration groups (0-3 months, 4-6 months, 7-12 months, >12 months, P = 0.08).In conclusion, a considerable proportion of the patients that participated in this study did not meet the thermal criteria set forth by the IASP and AMA. Further, there was no correlation between symptom duration and skin temperature difference., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Objectives: This study aims to compare the effectiveness of a bisphosphonate (pamidronate) and a steroid (prednisolone) in complex regional pain syndrome (CRPS) type I during four weeks of follow-up in hemiplegic stroke patients., Methods: Twenty-one hemiplegic stroke patients with CRPS type I were enrolled in the study. Patients were randomly assigned to receive either intravenous pamidronate (n = 11; total cumulative dose of 180 mg) or oral prednisolone (n = 10). Subjective pain and hand oedema (circumference of the middle finger, CMF, and the wrist, CW) were measured at baseline and at one, two and four weeks after the end of treatment., Results: Both groups showed significant improvement in subjective pain VAS scores at 1-week follow-up and this effect was maintained until 4-week follow-up. Time-by-group interactions were not significant at 4-week follow-up. The reduction of the CMF observed at 1-week follow-up in both groups was maintained until 4-week follow-up in the steroid group, but until 2-week follow-up in the pamidronate group. A significant change in CW was observed at 4-week follow-up in the pamidronate group. There were no significant adverse effects in either treatment group during the follow-up period., Conclusions: Intravenous pamidronate therapy was safe, well tolerated and appeared as effective as a steroid for pain control for post-stroke CRPS. However, this result should be interpreted with caution, since it included a relatively small number of patients. Further larger controlled studies followed over a longer period are needed to validate these findings and to determine clinical treatment standards.

Unlabelled: Complex regional pain syndrome (CRPS) is a potentially debilitating chronic pain syndrome with a poorly understood but likely neuroimmune/multifactorial pathophysiology associated with axonal injury. Based on the potential contribution of proinflammatory cytokines to CRPS pathogenesis and prior research with thalidomide, we investigated lenalidomide, a thalidomide derivative, for CRPS treatment. We conducted a phase II, randomized, double-blind, placebo-controlled study to evaluate the efficacy of oral lenalidomide 10 mg once daily in consenting patients with unilateral or bilateral CRPS type 1. The study comprised 12 weeks of treatment followed by a long-term extension. The primary efficacy outcome was reduced pain in the index limb, defined as ≥30% improvement from baseline using an 11-point numeric rating scale. One hundred eighty-four subjects enrolled. The primary endpoint was not met because equal proportions of treated (16.1%) and control (16.1%) subjects achieved the outcome; however, lenalidomide was well tolerated, with no evidence of neuropathy or major adverse effects. This study is the largest controlled, blinded clinical trial in subjects with chronic CRPS using the Budapest research criteria. It demonstrates the feasibility of conducting high-quality clinical trials in CRPS type 1 and provides considerations for designing future trials., Perspective: This article reports an adequately powered, controlled clinical trial in subjects with CRPS. Treatment and placebo were equally effective, but the study demonstrated that lenalidomide treatment is feasible in this population. The study provides examples to consider in designing future CRPS trials., (Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: Patients with complex regional pain syndrome type I (CRPS I) show a cortical reorganization with contralateral shrinkage of cortical maps in S1. The relevance of pain and disuse for the development and the maintenance of this shrinkage is unclear., Objective: Aim of the study was to assess whether short-term pain relief induces changes in the cortical representation of the affected hand in patients with CRPS type I., Study Design: Case series analysis of prospectively collected data., Methods: We enrolled a case series of 5 consecutive patients with CRPS type I (disease duration 3 - 36 months) of the non-dominant upper-limb and previously diagnosed sympathetically maintained pain (SMP) by reduction of the pain intensity of more than > 30% after prior diagnostic sympathetic block. We performed fMRI for analysis of the cortical representation of the affected hand immediately before as well as one hour after isolated sympathetic block of the stellate ganglion on the affected side., Statistics: Wilcoxon-Test, paired t-test, P < 0.05., Results: Pain decrease after isolated sympathetic block (pain intensity on the numerical rating scale (0 - 10) before block: 6.8 ± 1.9, afterwards: 3.8 ± 1.3) was accompanied by an increase in the blood oxygenation level dependent (BOLD) response of cortical representational maps only of the affected hand which had been reduced before the block, despite the fact that clinical and neurophysiological assessment revealed no changes in the sensorimotor function., Limitations: The interpretation of the present results is partly limited due to the small number of included patients and the missing control group with placebo injection., Conclusions: The association between recovery of the cortical representation and pain relief supports the hypothesis that pain could be a relevant factor for changes of somatosensory cortical maps in CRPS, and that these are rapidly reversible.

Pediatric complex regional pain syndrome (P-CRPS) offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks) but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state) with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning). Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects). These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects.

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.

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.

Unlabelled: There are indications of motor circuit changes in patients with complex regional pain syndrome (CRPS). Nevertheless, although several studies have analyzed motor behavior in CRPS, a relation with pain could not be detected. This might be explained by the use of cross-sectional designs in these studies, in which pain is considered as a trait- rather than a state-dependent variable. We therefore studied the time-dependent relation between pain and motor function in affected arms of 29 CRPS patients during their participation in a placebo-controlled ketamine study. Movement parameters (velocity, frequency, amplitude, and number of arrests) were assessed during a finger tapping task. Linear mixed model analysis of the effects of pain (numerical rating scale score), treatment (ketamine/placebo), and week (1, 3, 6, and 12 weeks after treatment) on the movement parameters revealed that pain intensity was significantly (inversely) related to motor function, irrespective of whether patients had received ketamine or placebo. Movement parameters changed 3-12% per point numerical rating scale change. Because patients were unaware of possible effects of ketamine on motor function, these findings suggest that motor function changes were mediated by, or occurred simultaneously with, changes in pain intensity. By improving motor function, pain relief may offer a window of opportunity for rehabilitation programs in CRPS., Perspective: This article provides evidence for a direct relation between pain and motor function in CRPS, which indicates that pain relief may be an important factor in the treatment of motor disturbances in this condition. These findings may help to advance our understanding of the pathways underlying motor disturbances in CRPS., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)

In 2005, a patient in my practice developed complex regional pain syndrome type 1 (CRPS 1) after bunion surgery. The condition was properly diagnosed within 4 weeks with a diagnostic technique that I routinely use to diagnose chronic musculoskeletal pain, and it was successfully treated. The tests, which are based on primitive and postural reflexes in infants, were adapted to reflect normal and abnormal motor behaviors in adults after provocation of reflexes of the autonomic nervous system (afferent C fibers in peripheral nerves). Approximately 60 days after my patient's operation, the tests indicated a positive reflex at the posterior tibial nerve in the operated foot. Surgery to remove an accessory ossicle from the talus adjacent to this nerve resolved the CRPS 1 within 2 weeks. Since CRPS 1 is a dysfunctional state of the autonomic regulatory control of pain, it was postulated that a test based on autonomic nerve function could isolate the source of CRPS 1. The Practical Application of Neurodiagnostic Evaluation process was shown to be diagnostic for the cause of acute CRPS 1 and to allow its reversal. Further evaluation of the test for diagnosis and treatment of CRPS is needed.

Unlabelled: Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle, or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either α(2)-adrenergic (α(2)A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent antiallodynic effects in rats with chronic postischemia pain, and the antiallodynic dose-response curves of PDE and PA inhibitors were shifted 2.5- to 10-fold leftward when combined with nonanalgesic doses of α(2)A receptor agonists or NO donors. Topical combinations also produced significant antiallodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy, and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 hours after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of α(2)A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain., Perspective: This article presents the synergistic antiallodynic effects of combinations of α(2)A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest that effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected areas., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: Ketamine is used as an analgesic for treatment of acute and chronic pain. While ketamine has a stimulatory effect on the cardiovascular system, little is known about the concentration-effect relationship. We examined the effect of S(+)-ketamine on cardiac output in healthy volunteers and chronic pain patients using a pharmacokinetic-pharmacodynamic modeling approach., Methods: In 10 chronic pain patients (diagnosed with complex regional pain syndrome type 1 [CRPS1] with a mean age 43.2 ± 13 years, disease duration 8.4 years, range 1.1 to 21.7 years) and 12 healthy volunteers (21.3 ± 1.6 years), 7 increasing IV doses of S(+)-ketamine were given over 5 minutes at 20-minute intervals starting with 1.5 mg with 1.5-mg increments. Cardiac output (CO) was calculated from the arterial pressure curve obtained from an arterial catheter in the radial artery. Ketamine and norketamine plasma concentrations were measured. A novel pharmacokinetic-pharmacodynamic model was constructed to quantify the direct stimulatory effect of ketamine on CO and the following adaptation/inhibition., Results: Significant differences in pharmacokinetic estimates were observed between study groups with 15% and 40% larger S(+)-ketamine S(+)-norketamine concentrations in healthy volunteers compared to CRPS1 patients. S(+)-ketamine had a dose-dependent stimulatory effect on CO in patients and volunteers. After infusion an inhibitory effect on CO was observed. Pharmacodynamic model parameters did not differ between CRPS1 patients and healthy volunteers. The concentration of S(+)-ketamine causing a 1 L/min increase in CO was 243 ± 54 ng/mL with an onset/offset half-life of 1.3 ± 0.21 minutes. The inhibitory component was slow (time constant of 67.2 ± 17.0 minutes)., Conclusions: S(+)-ketamine pharmacokinetics but not pharmacodynamics differed between study populations, related to differences in disease state (CRPS1 or not) or age. The dose-dependent effect of S(+)-ketamine on CO was well described by the biphasic dynamic model. The effect of S(+)-ketamine on CO was similar between study groups with respect to its stimulatory and inhibitory components, despite group differences in age and health.

The diagnosis of sympathetically maintained pain (SMP) is typically established by assessment of pain relief during local anesthetic blockade of the sympathetic ganglia that innervate the painful body part. To determine if systemic α-adrenergic blockade with phentolamine can be used to diagnose SMP, we compared the effects on pain of local anesthetic sympathetic ganglion blocks (LASB) and phentolamine blocks (PhB) in 20 patients with chronic pain and hyperalgesia that were suspected to be sympathetically maintained. The blocks were done inrandom order on separate days. Patients rated the intensity of ongoing and stimulus-evoked pain every 5 min before, during, and after the LASB and PhB. Patients and the investigator assessing pain levels were blinded to the time of intravenous administration of phentolamine (total dose 25-35 mg). The pain relief achieved by LASB and PhB correlated closely (r = 0.84), and there was no significant difference in the maximum pain relief achieved with the two blocks (t = 0.19, P > 0.8). Nine patients experienced a greater than 50% relief of pain and hyperalgesia from both LASB and PhB and were considered to have a clinically significant component of SMP. We conclude that α-adrenergic blockade with intravenous phentolamine is a sensitive alternative test to identify patients with SMP.

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.

Background: Pain Exposure Physical Therapy is a new treatment option for patients with Complex Regional Pain Syndrome type 1. It has been evaluated in retrospective as well as in prospective studies and proven to be safe and possibly effective. This indicates that Pain Exposure Physical Therapy is now ready for clinical evaluation. The results of an earlier performed pilot study with an n = 1 design, in which 20 patients with Complex Regional Pain Syndrome type 1 were treated with Pain Exposure Physical Therapy, were used for the design and power calculation of the present study.After completion and evaluation of this phase III study, a multi-centre implementation study will be conducted.The aim of this study is to determine whether Pain Exposure Physical Therapy can improve functional outcomes in patients with Complex Regional Pain Syndrome type 1., Methods/design: This study is designed as a single-blinded, randomized clinical trial. 62 patients will be randomized with a follow-up of 9 months to demonstrate the expected treatment effect. Complex Regional Pain Syndrome type 1 is diagnosed in accordance with the Bruehl/International Association for the Study of Pain criteria. Conventional therapy in accordance with the Dutch guideline will be compared with Pain Exposure Physical Therapy. Primary outcome measure is the Impairment level SumScore, restricted version., Discussion: This is the first randomized controlled study with single blinding that has ever been planned in patients with Complex Regional Pain Syndrome type 1 and does not focus on a single aspect of the pain syndrome but compares treatment strategies based on completely different pathophysiological and cognitive theories.

Unlabelled: Interventional pain management techniques play an important role in the multidisciplinary approach to management of complex regional pain syndrome (CRPS). In this preliminary study we compared the efficacy of continuous stellate ganglion (CSG) block with that of continuous infraclavicular brachial plexus (CIBP) block in management of CRPS type I of upper extremity., Methods: Thirty-three patients with CRPS type I of upper extremity were randomly assigned to either CSG or CIBP group. Patients were treated for 1 week with continuous infusion of 0.125% bupivacaine at 2and 5mL/h, respectively. Catheter was removed at 1 week and patients were followed up for 4 weeks. The outcome was evaluated in terms of neuropathic pain scale score (NPSS), edema scores (Grades 0-2), and range of motion (ROM) of all upper extremity joints (Grades 0-2)., Results: CIBP group showed statistically significant improvement in NPSS compared with CSG group during the first 12 hours after the procedures (P value <0.05). After 12 hours, the NPSS was comparable between the groups. At 4 weeks, both groups showed clinically significant improvement in edema score and ROM of all upper extremity joints when compared with the baseline., Conclusion: This preliminary study suggests that CIBP block and CSG block may be feasible and effective interventional techniques for the management of CRPS type I of upper extremities. Hence, we recommend a larger well-randomized, well-controlled, clinical trial to confirm our findings and determine if any significant difference exists between the groups in terms of long-term pain relief and functional restoration., (Wiley Periodicals, Inc.)

Complex regional pain syndrome (CRPS) (previously reflex sympathetic dystrophy) is a chronic pain condition usually resulting as a consequence of trauma or surgery. Though described occasionally after vascular surgery, it is distinctly rare after percutaneous cardiovascular procedures. We report a case of CRPS following trans- femoral catheterization-related groin pseudoaneurysm. To our knowledge, this is the first such report following transfemoral catheterization. A 36-year-old female underwent an electrophysiological study and AV node re-entry tachycardia ablation using the left femoral vein approach. One month later she presented complaining of numbness and tingling in her left foot with swelling and mild groin discomfort. A lower extremity duplex scan showed a left common femoral artery pseudoaneurysm that was partially thrombosed and subsequently resolved spontaneously. The patient had intractable symptoms of pain, temperature changes, color changes, and trophic changes of the left foot. Conventional angiography was done to rule out occlusive arterial disease but just showed very sluggish flow. Further evaluation with transcutaneous oxymetry and 3-phase bone scan was consistent with microvascular dysfunction and poor cutaneous blood flow suggestive of cold-type CRPS. In this case report, we also review the clinical features and the vascular changes associated with CRPS and discuss the pathophysiology of the syndrome from a cardiovascular specialist's perspective. Interventionalists should be aware that CRPS is a possible, albeit rare, condition that may follow many vascular procedures that they perform on a daily basis.

Type I complex regional pain syndrome is a neurophatic pain syndrome whose physiopathology is not yet fully understood. It mainly affects limb extremities and often occurs after local trauma. There is no consensus on the treatment, but early intervention seems important, particularly in the context of Physical Medicine and Rehabilitation. The authors review physiopathologic mechanisms and point to importance of an early diagnosis, since failure to recognize this clinical picture and the consequent delay in treatment may cause serious functional impairments.

Complex regional pain syndrome (CRPS) is a highly painful, limb-confined condition, which arises usually after trauma. It is associated with a particularly poor quality of life, and large health-care and societal costs. The causes of CRPS remain unknown. The condition's distinct combination of abnormalities includes limb-confined inflammation and tissue hypoxia, sympathetic dysregulation, small fibre damage, serum autoantibodies, central sensitization and cortical reorganization. These features place CRPS at a crossroads of interests of several disciplines including rheumatology, pain medicine and neurology. Significant scientific and clinical advances over the past 10 years hold promise both for an improved understanding of the causes of CRPS, and for more effective treatments. This review summarizes current concepts of our understanding of CRPS in adults. Based on the results from systematic reviews, treatment approaches are discussed within the context of these concepts. The treatment of CRPS is multidisciplinary and aims to educate about the condition, sustain or restore limb function, reduce pain and provide psychological intervention. Results from recent randomized controlled trials suggest that it is possible that some patients whose condition was considered refractory in the past can now be effectively treated, but confirmatory trials are required. The review concludes with a discussion of the need for additional research.

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.

Complex regional pain syndrome-type I (CRPS-I; reflex sympathetic dystrophy) is a chronic pain condition that usually follows a deep-tissue injury such as fracture or sprain. The cause of the pain is unknown. We have developed an animal model (chronic post-ischemia pain) that creates CRPS-I-like symptomatology. The model is produced by occluding the blood flow to one hind paw for 3 hours under general anesthesia. Following reperfusion, the treated hind paw exhibits an initial phase of hyperemia and edema. This is followed by mechano-hyperalgesia, mechano-allodynia, and cold-allodynia that lasted for at least 1 month. Light microscopic analyses and electron microscopic analyses of the nerves at the site of the tourniquet show that the majority of these animals have no sign of injury to myelinated or unmyelinated axons. However, electron microscopy shows that the ischemia-reperfusion injury produces a microvascular injury, slow-flow/no-reflow, in the capillaries of the hind paw muscle and digital nerves. We propose that the slow-flow/no-reflow phenomenon initiates and maintains deep-tissue ischemia and inflammation, leading to the activation of muscle nociceptors, and the ectopic activation of sensory afferent axons due to endoneurial ischemia and inflammation. These data, and a large body of clinical evidence, suggest that in at least a subset of CRPS-I patients, the fundamental cause of the abnormal pain sensations is ischemia and inflammation due to microvascular pathology in deep tissues, leading to a combination of inflammatory and neuropathic pain processes. Moreover, we suggest a unifying idea that relates the pathogenesis of CRPS-I to that of CRPS-II. Lastly, our hypothesis suggests that the role of the sympathetic nervous system in CRPS-I is a factor that is not fundamentally causative, but may have an important contributory role in early-stage disease.

Background: Patients suffering from Complex Regional Pain Syndrome commonly complain of substantial limitations in their activities of daily living. The Radboud Skills Questionnaire measures alterations in the level of disability of patients with Complex Regional Pain Syndrome, but this instrument is currently not available in German. The goals of our study were to translate the Dutch Radboud Skills Questionnaire into German and to assess its external criterion validity with the German version of the Disabilities of the Arm, Shoulder and Hand Questionnaire., Methods: We translated the Radboud Skills Questionnaire according to published guidelines. Demographic data and validity were assessed in 57 consecutive patients with Complex Regional Pain Syndrome 1 of the upper extremity. Information on age, duration of symptoms, type of Complex Regional Pain Syndrome 1 and type of initiating event was obtained. We assessed the external criterion validity by comparing the German Radboud Skills Questionnaire and the German Disabilities of the Arm, Shoulder and Hand Questionnaire and calculated the prediction intervals., Results: Score values ranged from 55.4 +/- 22.0 for the Disabilities of the Arm, Shoulder and Hand Questionnaire score and 140.1 +/- 39.2 for the Radboud Skills Questionnaire. We found a high correlation between the Radboud Skills Questionnaire and the Disabilities of the Arm, Shoulder and Hand Questionnaire (R2 = 0.83)., Conclusion: This validation of the Radboud Skills Questionnaire demonstrates that this German version is a simple and accurate instrument to assess and quantify disabilities of patients suffering from Complex Regional Pain Syndrome 1 of the upper extremity for clinical and research purposes.

Background: The Dutch Walking Stairs, Walking Ability and Rising and Sitting Questionnaires are three validated instruments to measure physical activity and limitations in daily living in patients with lower extremity disorders living at home of which no German equivalents are available. Our scope was to translate the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires into German and to verify its concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale., Methods: We translated the Walking Stairs, Walking Ability and Rising and Sitting Questionnaires according to published guidelines. Demographic data and validity were assessed in 52 consecutive patients with Complex Regional Pain Syndrome 1 of the lower extremity. Information on age, duration of symptoms, type of Complex Regional Pain Syndrome 1 and type of initiating event were obtained. We assessed the concurrent validity in the two domains pain and activities in daily living by comparing them with the corresponding measures on the Visual Analogue Scale., Results: We found that variability in the German Walking Stairs, Walking Ability and Rising and Sitting Questionnaires was largely explained by measures of pain and activities in daily living on the Visual Analogue Scale., Conclusion: Our study shows that the domains pain and activities in daily living are properly represented in the German versions of the Walking Stairs, Walking Ability and Raising and Sitting Questionnaires. We would like to propagate their use in clinical practice and research alike.

Background: Complex regional pain syndrome type 1 (CRPSt1) of the upper limb is a painful and debilitating condition, frequent after stroke, and interferes with the rehabilitative process and outcome. However, treatments used for CRPSt1 of the upper limb are limited., Objective: . This randomized controlled study was conducted to compare the effectiveness on pain and upper limb function of mirror therapy on CRPSt1 of upper limb in patients with acute stroke., Methods: . Of 208 patients with first episode of unilateral stroke admitted to the authors' rehabilitation center, 48 patients with CRPSt1 of the affected upper limb were enrolled in a randomized controlled study, with a 6-month follow-up, and assigned to either a mirror therapy group or placebo control group. The primary end points were a reduction in the visual analogue scale score of pain at rest, on movement, and brush-induced tactile allodynia. The secondary end points were improvement in motor function as assessed by the Wolf Motor Function Test and Motor Activity Log., Results: . The mean scores of both the primary and secondary end points significantly improved in the mirror group (P < .001). No statistically significant improvement was observed in any of the control group values (P > .001). Moreover, statistically significant differences after treatment (P < .001) and at the 6-month follow-up were found between the 2 groups., Conclusions: . The results indicate that mirror therapy effectively reduces pain and enhances upper limb motor function in stroke patients with upper limb CRPSt1.

Pain-related impairment assessment by the fifth edition of the American Medical Association Guides had many ambiguous points, and therefore, it was not applicable directly in Korea. Several disputable pain disorders were excluded from the list of impairment evaluation, and complex regional pain syndrome was chosen as the first object of impairment evaluation. Scales such as Korean version of modified Barthel index for assessing the activity of daily livings and Beck Depression Inventory for assessing depression were added, and pain severity, pain treatment, pain behavior, etc. were scored. In order to objectify as much as possible and to remove the room for misuse, we develop a new rating system based on the concept of total score.

Introduction: Complex regional pain syndrome type I (CRPS I) is a neuropathic pain disorder of unclear etiology. It commonly follows a trivial injury and is characterized by spontaneous pain manifesting regionally that is disproportionate to the inciting event. Associated signs and symptoms include allodynia, hyperalgesia, edema, sudomotor, vasomotor abnormalities, and trophic changes. Although multiple modalities exist to treat CRPS I, significant disability, diminution in quality of life, and reduction in overall health often accompany the syndrome., Case: A case of a 57-year-old man with CRPS I who was treated with spinal cord stimulation (SCS) after failing conservative therapy is presented. One month following treatment, he experienced complete symptom resolution such that stimulation was subsequently discontinued without recurrence over the 1-year follow-up period., Conclusions: To date there is currently no reliably validated "cure" for CRPS. There has only been one recent report where SCS resulted in the complete eradication of the signs and symptoms associated with CRPS. This series involved adolescent girls aged 11-14 years of age, who tend to have a more benign and self-limited treatment course than that seen in adults. This raises the question as to whether a "neural switch" exists, and if so, where it is located. We postulate that the inter-neuronal connections between the central and peripheral nervous systems implicated by the current pathophysiological model is the most plausible site of this "neural switch," and that reorganization of this interface can account for the ability of SCS to effect a complete "cure" in CRPS.

Background: In patients with complex regional pain syndrome type 1 (CRPS1), some improvement can be achieved by the administration of ketanserin, a 5-HT(2A) receptor antagonist. We measured plasma levels of serotonin (5-HT) during CRPS1 and correlated these levels with disease characteristics., Methods: Plasma 5-HT was measured in 35 patients who had CRPS1 for 3 yr and compared with 35 age-matched healthy controls., Results: The plasma 5-HT levels were 411 +/- 263 nmol/L and 29 +/- 18 nmol/L, respectively (P < 0.001). No correlations with disease characteristics were observed., Conclusions: The markedly elevated levels of plasma 5-HT in CRPS1 patients suggest a role for 5-HT during the course of this disease. However, because of the lack of correlations with distinct disease characteristics, 5-HT is probably one of a number of mediators in CRPS1.

Background: Complex regional pain syndrome type 1 can be difficult to treat. The purpose of this study was to compare the safety and efficacy of two therapeutic options: percutaneous radiofrequency thermal lumbar sympathectomy and lumbar sympathetic neurolysis., Methods: We randomized 20 patients to receive percutaneous radiofrequency lumbar sympathectomy or lumbar sympathetic neurolysis with phenol 7% in lower limb complex regional pain syndrome type 1. The study end points were pain relief and side effects., Results: Within each group, there were statistically significant reductions from baseline in various pain scores after the procedure. However, there was no statistically significant difference in mean pain scores between the groups., Conclusions: Based on this pilot study, radiofrequency lumbar sympathectomy may be comparable to phenol lumbar sympathectomy. A larger trial is required to confirm these findings.

Objective: In this study, we assessed the validity of skin surface temperature recordings, based on various calculation methods applied to the thermographic data, to diagnose acute complex regional pain syndrome type 1 (CRPS1) fracture patients., Methods: Thermographic recordings of the palmar/plantar side and dorsal side of both hands or feet were made on CRPS1 patients and in control fracture patients with/without and without complaints similar to CRPS1 (total in the three subgroups = 120) just after removal of plaster. Various calculation methods applied to the thermographic data were compared using receiver operating characteristics analysis to obtain indicators of diagnostic value., Results: There were no significant differences in demographic data and characteristics among the three subgroups. The most pronounced differences among the subgroups were vasomotor signs in the CRPS1 patients. The involved side in CRPS1 patients was often warmer compared with the noninvolved extremity. The difference in temperature between the involved site and the noninvolved extremity in CRPS1 patients significantly differed from the difference in temperature between the contralateral extremities of the two control groups. The largest temperature difference between extremities was found in CRPS1 patients. The difference in temperature recordings comparing the palmar/plantar and dorsal recording was not significant in any group. The sensitivity and specificity varied considerably between the various calculation methods used to calculate temperature difference between extremities. The highest level of sensitivity was 71% and the highest specificity was 64%; the highest positive predictive value reached a value of 35% and the highest negative predictive 84%, with a moderate 0.60 > or = area under the curve < or = 0.65., Conclusion: The validity of skin surface temperature recordings under resting conditions to discriminate between acute CRPS1 fracture patients and control fracture patients with/without complaints is limited, and only useful as a supplementary diagnostic tool.

Background: In complex regional pain syndrome type 1 (CRPS1) pro-inflammatory mediators and vascular changes play an important role in the sustained development and outcome of the disease. The aim of this study was to determine the involvement of vasoactive substances endothelin-1 (ET-1) and nitric oxide (NO) during early chronic CRPS1., Methods: Included were 29 patients with CRPS 1 who were diagnosed during the acute stage of their disease and observed during follow-up visits. Disease activity and impairment were determined and artificial suction blisters were made on the CRPS1 and the contralateral extremities for measurements of IL-6, TNF-alpha, ET-1 and nitrate/nitrite (NOx)., Results: The levels of IL-6, TNF-alpha and ET-1 in blister fluid in the CRPS1 extremity versus the contralateral extremity were significantly increased and correlated with each other, whereas NOx levels were decreased., Conclusion: The NOx/ET-1 ratio appears to be disturbed in the intermediate stage of CRPS, resulting in vasoconstriction and consequently in a diminished tissue blood distribution.

Objective: To explore the mechanism of post-stroke reflex sympathetic dystrophy (RSD) patients electromyographic abnormality and confirm its clinical value., Methods: Fifty patients with first-onset stroke, aged 33 - 78, including 30 with RSD and 20 without RSD, underwent needle electromyography (EMG) to test the nerve conduction velocity (NCV) and sensory nerve conduction velocity (SCV) of bilateral median nerves, and the number and position of spontaneous EMG activity of bilateral short abductor muscles of thumb and abductor muscles little finger., Results: The median nerve compound muscle action potential (CMAP) amplitude of the affected upper extremities of the RSD group was 8.6 mV +/- 2.9 mV, significantly lower than that of the non-RSD group (13.2 mV +/- 4.6 mV, P < 0.01). The incidence of spontaneous electrical potential of the RSD group was 100%; significantly higher than hat of the non-RSD group (65%, P < 0.001). The quantity of spontaneous EMG activity on the short abductor muscles of thumb and abductor muscles little finger was increased in the RSD group (P < 0.01). The motor nerve conduction velocity and electrophysiological presentation of sensory nerve of these 2 groups were all normal and without significant differences between them., Conclusion: Partial axonal degeneration occurs on the distal motor never fibers of the affected upper extremity of the RSD patients, which may be related to subsequent peripheral nerve injury after central nerve system impairment.

Background: Complex Regional Pain Syndrome type 1 (CRPS1) is a clinical diagnosis based on criteria describing symptoms of the disease. The main aim of the present study was to compare the sensitivity and specificity of calculation methods used to assess thermographic images (infrared imaging) obtained during temperature provocation. The secondary objective was to obtain information about the involvement of the sympathetic system in CRPS1., Methods: We studied 12 patients in whom CRPS1 was diagnosed according to the criteria of Bruehl. High and low whole body cooling and warming induced and reduced sympathetic vasoconstrictor activity. The degree of vasoconstrictor activity in both hands was monitored using a videothermograph. The sensitivity and specificity of the calculation methods used to assess the thermographic images were calculated., Results: The temperature difference between the hands in the CRPS patients increases significantly when the sympathetic system is provoked. At both the maximum and minimum vasoconstriction no significant differences were found in fingertip temperatures between both hands., Conclusion: The majority of CRPS1 patients do not show maximal obtainable temperature differences between the involved and contralateral extremity at room temperature (static measurement). During cold and warm temperature challenges this temperature difference increases significantly. As a result a higher sensitivity and specificity could be achieved in the diagnosis of CRPS1. These findings suggest that the sympathetic efferent system is involved in CRPS1.

Complex regional pain syndrome (CRPS) types I and II are neuropathic pain disorders that develop as an exaggerated response to a traumatic lesion or nerve damage, that generally affects the extremities, or as the consequence of a distant process such as a stroke, spinal lesion or myocardial infarction. It rarely appears without an apparent cause. CRPS of upper limbs after stroke is frequently today called shoulder-hand syndrome (SHS). The onset and severity of SHS appears to be related with the aetiology of the stroke, the severity and recovery of motor deficit, spasticity and sensory disturbances. Another important aetiological factor is glenohumeral subluxation. The physiopathology of the disease is still not known. In CRPS, there is an exaggerated inflammatory response and some chemical mediators have been identified and are present in the inflammatory soup around the primary afferent fibres that, through different processes, can induce hyper-excitability of the afferent fibres (peripheral sensitization). It is hypothesized that a localized neurogenic inflammation is at the basis of oedema, vasodilation and hyperhidrosis that are present in the initial phases of CRPS. The repeated discharge of the C fibres causes an increased medullary excitability (central sensitization). Another important factor is the reorganisation of the central nervous system, and in particular this appears to affect the primary somatosensory cortex. The central role of the sympathetic nerve is presently in doubt. However, it is thought that a sub-group of CRPS patients exists in whom a predominant factor is the hyper-activity of the sympathetic nervous system, and that it responds positively to sympathetic block. Diagnosis is clinical and there are no specific tests, nor pathognomic symptoms to identify this disease with certainty. Diagnosis of CRPS after stroke appears more complex than in other pathological situations: the paretic upper arm frequently appears painful, oedematose, with altered heat and tactile sensations and slightly dystrophic skin within a non-use syndrome. Some investigations can aid differential diagnosis with other diseases. Treatment may be non-pharmacological, pharmacological, with psychotherapy, regional anaesthesia, neuromodulation and sympathectomy. In any case there is little evidence that supports the efficacy of the interventions normally used to treat or prevent CRPS-SHS. The key to effective treatment undoubtedly lies in a an expert multidisciplinary team that is co-ordinated and motivated and that treats the disorder with individualised therapy.

Unlabelled: We describe a 12-year-old patient with severe, protracted complex regional pain syndrome type I. His pain did not respond to gabapentin, amitriptyline, physical therapy, opioids, or nonsteroidal drugs. Sympathetic or regional block was not attempted because of persistent bacteremia and severe local sepsis. His pain responded dramatically to the addition of oxcarbazepine, with rapid improvement in his symptoms and functional status. We suggest that oxcarbazepine might be a useful adjunct in the treatment of gabapentin-resistant complex regional pain syndrome type I in children and should be considered., Perspective: Oxcarbazepine's antinociceptive effect is mediated via sodium channel inhibition in neuropathic models and by inhibition of substance P and prostaglandins in anti-inflammatory models. The efficacy of oxcarbazepine in this patient might be attributable to these mechanisms or possibly to synergism with either gabapentin or the anti-inflammatory effects produced by amitriptyline.

Objective: To evaluate the effects of the antiresorptive agent alendronate at a daily oral dose of 40 mg in patients with posttraumatic complex regional pain syndrome type I (CRPS I) of the lower extremity., Methods: Forty patients were enrolled in this 8-week randomized, double-blind, placebo-controlled study of alendronate therapy for CRPS I, a condition associated with regional osteoclastic overactivity. An optional 8-week open extension of alendronate therapy (weeks 12-20) was available after a 4-week period without therapy. Clinical assessments included joint mobility, edema of the lower extremity, tolerance to pressure in the lower extremity, and levels of spontaneous pain. Urinary levels of type I collagen N-telopeptide (NTX) were assessed by enzyme-linked immunosorbent assay. Patients were examined at weeks 4, 8, 12, 16, 20, and 24. Statistical analysis included two-way factorial analysis of variance., Results: In contrast to placebo-treated patients (n = 20), all of the alendronate-treated patients (n = 19) exhibited a marked and sustained improvement in levels of spontaneous pain, pressure tolerance, and joint mobility, as well as a significant reduction in urinary levels of NTX at weeks 4 and 8. The improvement was maintained at week 12. Twelve patients from each treatment group volunteered for the 8-week open trial, and all of them had a positive response to alendronate., Conclusion: Our findings support the use of oral alendronate in posttraumatic CRPS I. By reducing local acceleration of bone remodeling, alendronate might relieve pain by effects on nociceptive primary afferents in bone, pain-associated changes in the spinal cord, and possibly also through a central mechanism.