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Background: Because of the unclear pathophysiology and the lack of consensus on the gold standard treatment of complex regional pain syndrome (CRPS), management requires a multidisciplinary approach, with the use of various treatment modalities. Nonetheless, no studies have ever been conducted to uncover the potential of mecobalamin as a treatment for CRPS type 1. Hence, the aim of this clinical trial was to evaluate the effects of mecobalamin on the functional outcomes of patients with CRPS type 1 of the foot and ankle, the total amount of pregabalin ingested, and the duration of pregabalin use in each patient., Methods: Forty-seven patients diagnosed with acute CRPS type 1 of the foot and ankle were recruited. Patients were randomly allocated into a control group (23 patients) and a mecobalamin group (24 patients), both receiving similar pain control medications and rehabilitation programs. Three divided doses of mecobalamin 1.5 mg/d were provided to the mecobalamin group for the first 3 months, whereas a placebo was administered to the control group. Data were collected from the pretreatment period, and from 1, 3, 6, and 12 months following the treatment., Results: Both groups had similar demographics. The mean Foot and Ankle Ability Measure (FAAM) activities of daily living (ADL) and FAAM-sport scores in the mecobalamin group at 3 months were 74.5 ± 17.9 and 56.3 ± 22.9, whereas the mean FAAM-ADL and FAAM-sport scores in the placebo group at 3 months were 62.2.5 ± 15.2 and 43.4 ± 14.9, respectively ( P  < .05). The 36-Item Short Form Health Survey (SF-36) mental health subscale after 3 months were 83.3 ± 9.5 points and 75.8 ± 12.6 points in the mecobalamin and placebo group, respectively ( P  < .05). However, at other time points of assessment (1, 6, and 12 months), the improvement in symptoms was not distinguishable between the 2 groups. Both the amount and duration of total pregabalin required to achieve similar improvements in pain scores were significantly lower in the mecobalamin group than the control group., Conclusion: This small study revealed an improvement of the functional outcomes in patients with CRPS type 1 of the foot and ankle who received mecobalamin instead of a placebo at 3 months that was not sustained at 6 and 12 months. We identified an average 39% total reduction in the amount of total pregabalin used in the mecobalamin group in the first 12 months., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Disclosure forms for all authors are available online.

Background: Complex regional pain syndrome type II (CRPS-II) is a rare condition associated with peripheral nervous system lesions. Its localized distribution in the fingers is unique, and its treatment is unclear., Case Description: A 56-year-old male presented to the emergency department with a saw-cut index finger injury with associated tendon and nerve injuries. After surgery, he was admitted to physical therapy (PT) with persistent pain, joint stiffness, allodynia, and trophic changes compatible with CRPS-II localized in the index finger. The diagnosis was confirmed after applying the Budapest Criteria, and PT was progressive and individualized according to the patient's needs, including graded motor imagery, mobilizations, exercises, and education., Outcomes: After 12 weeks of PT, a clinically significant decrease in pain intensity and improvements in mobility and index finger and upper limb functionality was observed, reducing CRPS symptomatology., Discussion: This report provides information about a unique case of a localized form of CRPS-II. After reviewing the literature on clinical cases of both CRPS-II and localized forms of CRPS, we highlight that the clinical features of this patient and his positive therapeutic response support the importance of translating the scientific evidence on CRPS into clinical practice.

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.

Objectives: Complex regional pain syndrome (CRPS) is a painful disease that leads to chronic pain and disability. Bisphosphonates are largely used in the real-life for the treatment of CRPS, but data on long-term effectiveness and its predictors are lacking., Methods: We conducted a longitudinal observational study on patients with type I CRPS treated with IV neridronate (100 mg on 4 occasions). Clinical and demographic characteristics were collected at baseline, after 3 months (M3) and after 12 months (M12). Multivariable logistic regression was employed to determine the factors associated with long-term response to treatment., Results: 103 patients with type I CRPS treated with IV neridronate were included in the study. Mean VAS pain at baseline was 79.1 mm and decreased significantly at M3 (-45.9 mm, 95% CI 40.1 to 51.8) and M12 (-61.6 mm, 95% CI 55.3 to 67.9). Hyperalgesia and allodynia resolved in 84.3% and 88.1% of patients at M12. Loss of motion resolved in 53.5% of patients. The predictors of excellent response were gender (male better), predisposing event to CRPS (no event being better than any predisposing event), site of CRPS (lower limb being better), and early response at M3 on VAS pain (2.5 times the chance of being excellent responder every 10 mm decrease)., Conclusions: In this real-life study neridronate was associated with rapid and progressive improvement of symptoms of CRPS which was maintained up to 3 years of follow-up. The predictors of excellent response were early response, lower limb localisation, absence of predisposing events and male gender.

Background and Objective: Complex regional pain syndrome (CRPS) is a multifaceted disorder resulting in an abnormal pain response to tissue injury. Among key CRPS features are neurogenic inflammation, maladaptive plasticity, and vasomotor dysfunction, which can result in severe pain and disability. Spinal cord stimulation (SCS) is an efficacious treatment for several chronic pain conditions and may improve pain and life quality in CRPS patients with CRPS. However, little information exists regarding perioperative outcomes of patients with CRPS undergoing surgical implantation of an SCS device., Methods: Patients were included if they underwent an SCS procedure at our institution between 2008 and 2016 for chronic pain. Cases were excluded if the procedure involved stimulator removal or if it was an outpatient procedure. Multivariate regression assessed the effect of CRPS and other clinical variables on perioperative outcomes., Results: Eighty-one inpatient SCS implantation cases for chronic pain were included, with 9 patients (11.1%) having a CRPS diagnosis. The CRPS cohort received higher mean quantities of intraoperative opioids and had a lower proportion of patients reporting meaningful pain reduction (16.7%) in the 24-hour postoperative setting compared with patients without CRPS (35.9%), although this was not statistically significant. Multivariate regression modeling suggested that CRPS was a significant predictor of increased odds of extended time to the postanesthesia care unit discharge (P = 0.0406) and higher direct costs of hospitalization (P = 0.0326)., Conclusions: Our data suggest that CRPS may pose several unique risks in the perioperative period after inpatient SCS implantation. These findings support the need for future prospective investigations examining risks and outcomes for SCS procedures in this population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Complex regional pain syndrome (CRPS) is a painful condition of a limb characterized by a constellation of symptoms. Little is known about the clinical features of pediatric CRPS, with fewer than a dozen studies published to date. The aim of this study was to explore the clinical course of pediatric CRPS, with emphasis on clinical features and disease outcomes. A secondary aim was to discern differences in clinical features of pediatric CRPS with and without related movement disorders, and between children who had a favorable and unfavorable outcome., Materials and Methods: We carried out a retrospective chart review of children with CRPS who presented to a pediatric Chronic Pain Clinic in Canada over a 5-year period (2012 to 2016)., Results: The study identified 59 children with CRPS (mean age: 12.7±2.5; 74.6% female; 72.9% lower extremity). In total, 87% (n=48) of children experienced complete resolution or significant improvement of CRPS, with a relapse rate of 15%. Overall, 25% (n=15) had a CRPS-related movement disorder. There were no differences in the clinical features of pediatric CRPS with or without related movement disorders. Children who experienced a favorable outcome had a significantly shorter symptom duration at the initial visit in comparison with children who experienced an unfavorable outcome., Discussion: In this cohort, pediatric CRPS was most common in girls around the age of 12, usually in the lower extremity, and most experienced a favorable outcome. Further research is needed to better understand the prognosis and relapse rate of pediatric CRPS.

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.)

Complex regional pain syndrome I (CRPS-I) is a chronic painful pathology still undertreated. CTK 01512-2 is a recombinant version of the spider peptide Phα1β, and it functions as a voltage-gated calcium channel blocker and a transient receptor potential ankyrin 1 (TRPA1) antagonist with antinociceptive effect in different pain models. Here, we investigate the mechanisms involved in the acute and chronic nociceptive phases of a model of CPRS-I in mice and assess the antinociceptive effect of CTK 01512-2 using this model. Adult male and female mice C57BL/6 (20-30 g) were used to determine mechanical (von Frey test) or cold (acetone test) allodynia induction. Inflammatory parameters (serum and tibial nerve lactate levels, hind paw temperature and edema, or tissue cell infiltration) were evaluated after chronic post-ischemia pain (CPIP, a model of CPRS-I) induction. Anti-inflammatory and anti-neuropathic drugs or CTK 01512-2 were tested. First, we detected that CPIP-induced mechanical and cold allodynia in male and female mice in a similar way. In the acute phase (1 day after CPIP), an increase in inflammatory parameters were observed, as well as the anti-allodynic effect of anti-inflammatory compounds. In the chronic phase (17 days after CPIP), mice exhibited mechanical and cold allodynia, and anti-neuropathic drugs induced antinociception, while no inflammatory alterations were found. CTK 01512-2 reversed the CPIP allodynic effect in both nociceptive phases. Thus, this CPRS-I model can be used to understand the mechanisms involved in CPRS-I induced pain and inflammation. Besides, we observed that CTK 01512-2 has a valuable antinociceptive effect in this pain model., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Objective: To evaluate whether combining fluidotherapy to conventional rehabilitation program provides additional improvements on pain severity, upper extremity functions, and edema volume in patients with poststroke complex regional pain syndrome (CRPS)., Design: Randomized controlled trial., Setting: Training and research hospital., Participants: Thirty hemiplegic patients with subacute stage CRPS type-1 of the upper extremity., Interventions: The patients randomly divided into 2 groups. Both groups received a 3 week conventional rehabilitation program (5 days/week, 2-4 hours/day). Experimental group received 15 sessions additional fluidotherapy application to the affected upper extremity (40 °C, 20 minutes in continuous mode, 5 sessions/week)., Main Outcome Measures: We evaluated the distal upper arm edema with a volumeter. Other used clinical assessment scales were Brunnstrom recovery stages of the arm and hand for motor recovery, motor items of the functional independence measure for functional status, visual analog scale for pain severity, and the painDETECT questionnaire for presence and the severity of neuropathic pain., Results: The mean age of the participants was 64.3 ± 11.66 (28-84). At the post-treatment evaluation, significant improvements were revealed regarding to the edema volume, pain visual analog scale, painDETECT and functional independence measure scores, and the Brunnstrom stages of upper extremity and hand in both groups (P < .05). But among the parameters mentioned above, only the decrease in edema volume and the painDETECT scores were greater in fluidotherapy group than the control group (P < .05)., Conclusions: Addition of the fluidotherapy to the conventional rehabilitation program provides better improvements on neuropathic pain and edema volume in subacute stage poststroke CRPS., (Copyright © 2019. Published by Elsevier Inc.)

Local osteopenia and altered bone metabolism are major complications of complex regional pain syndrome (CRPS), but quantitative assessment is difficult unless using X-ray or dual-energy X-ray absorptiometry. Ultrasound-based measurement of bone density (UBD) is a possible alternative but has never been used to detect unilateral disease such as CRPS. Therefore, the main outcome measure of this prospective study was the diagnostic utility of UBD in patients with lower-limb CRPS. Second, we compared the extent of unilateral and contralateral calcaneal bone density to that of other conditions with unilateral pain, general osteoporosis, and healthy subjects. Calcaneal osteodensitometry was bilaterally examined using ultrasound-based methodology. Bone mineral density values were converted to Z-scores based on age- and sex-dependent reference values. All patients completed a functional and an osteoporosis risk questionnaire. In patients with CRPS (n = 18), the bone mineral density values and Z-scores were significantly lower in both the affected (mean ± SD: 0.40 ± 0.08 and -1.1 ± 0.8, respectively) and nonaffected (0.46 ± 0.09 and -0.6 ± 0.9, respectively) limbs than in patients (n = 40) with other unilateral pain syndromes (affected: 0.51 ± 0.1 and -0.2 ± 1.1, respectively; nonaffected: 0.54 ± 0.11 and 0 ± 0.9, respectively) and healthy subjects (right side: 0.6 ± 0.1 and 0.1 ± 0.9, respectively). Conversely, in patients with known systemic osteoporosis, the Z-scores were lower bilaterally with smaller side-to-side differences than in those with CRPS (P < 0.05). Compared with subjects suffering from long-term CRPS (≥2.4 years), patients with shorter disease duration exhibited significantly lower Z-scores (P < 0.05). In conclusion, UBD revealed that CRPS is associated with both local and systemic alterations of bone metabolism.

Background: Reflex sympathetic dystrophy (RSD) is the common complication among stroke and cerebral injury patients, which is lack of safe and effective treatment. Electroacupuncture (EA) may potentially be a reliably therapy, but the evidence is insufficiency., Methods: Cochrane Library, MEDLINE, Embase, Chinese National Knowledge Infrastructure, Wan Fang Data, the Chinese Biology Medicine disc, etc., were searched, until July 20, 2018. We included random control trials that contrast EA with conventional rehabilitation therapy for the treatment of RSD. Main outcomes were visual analog scale score and Fugl-Meyer upper limb motor function scoring scale, other outcomes such as Barthel index, and hand swelling score were also collected. Data in included studies were extracted into an excel and pooled by Stata/MP 14.1., Results: We incorporated 13 studies involving 1040 RSD patients and outcomes were from 2 to 6 weeks' follow-up. The analgesic effect between 2 groups had statistically significant difference (weighted mean difference [WMD] = -1.122, 95% confidence interval [CI] [-1.682 to -.562], P = .000], a statistical difference existed in improving dysfunction between 2 groups: (WMD = 6.039, 95% CI [2.231-.916], P = .000). EA groups had a better effect on improving activities of daily life abilities (WMD = 12.170, 95% CI [6.657-17.682], P < .00011] and better detumescence effect (WMD = -.800, 95% CI [-1.972 to -.212], P = .000] contrast to conventional rehabilitation therapy., Conclusions: This meta-analysis supports that EA has a positive effect on alleviating pain, improving limb dysfunction, and promoting activities of daily living. On account of moderate-quality random control trials and high heterogeneity, further high-quality studies are imperative to optimize the EA treatment program., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Hypersensitivity and altered sweating are often present in neuropathy patients. Nerve lesions are known to produce sudomotor dysfunctions but also patients suffering from complex regional pain syndrome, CRPS1-a condition without a nerve lesion-present with sweating disorders., Methods: Using proton nuclear magnetic resonance of sweat water, we quantified sweat output of mice suffering from a nerve lesion or a bone fracture without nerve lesion and correlated their sweating with behavioural paw hypersensitivity accessed in von Frey testings, water applications and weight-bearing measured with an incapacitance metre., Results: Lesioned animals sweat less and are hypersensitive compared to healthy controls, as expected. Fractured animals on the injured side sweat less acutely after the injury but more in the chronic phase. They are hypersensitive acutely as well as chronically after the fracture. These findings resemble human bone trauma patients in the acute phase and CRPS patients in the chronic phase., Conclusions: Sweating disorders are present both in neuropathic animals and in those with a bone fracture without nerve lesions, and autonomic dysfunctions might be considered as an important component in the aetiology of neuropathies., Significance: Sweat output changes in mice after bone trauma, potentially indicative of posttraumatic processes leading to CRPS in humans., (© 2018 European Pain Federation - EFIC®.)

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.

Complex Regional Pain Syndrome type 1 (CRPS-1) is a disabling painful disease whose hallmark is pain disproportionate to inciting event. CRPS is also characterized by symptoms and signs, such as vasomotor, sudomotor, trophic and motor changes. Therapeutic approach of CRPS-1 still remains a challenge for clinicians treating a disease with potential heavy consequences on patient prognosis. In the past years, the treatment with bisphosphonates (BPs) has gained some success as confirmed by the results of a number of meta-analyses. The aim of this paper is to point out the pivotal role of bone in CRPS pathogenesis. The efficacy of BPs is likely to be related to bone tissue involvement in the early pathophysiological steps of the disease, as demonstrated by evidences highlighting the central role of bone in the initial phases. Bone can become a source of inflammatory cytokines when triggered by a direct injury. Moreover, peptidergic fibers that innervate both mineralized bone and bone marrow can play a role in triggering or maintaining the microvascular disturbance at bone level. Indeed, bone involvement is consistent with the mineralization disturbance as well as the results of instrumental investigations (e.g., MRI, bone scan). In this regard, an intriguing issue relies on the excellent therapeutic response to BPs treatment of other diseases (e.g., Transient Osteoporosis of the Hip and Regional Migratory Osteoporosis) that share with CRPS-1 some clinical and instrumental features.

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.

Background: Complex regional pain syndrome (CRPS) is associated with deficits in limb recognition. The purpose of our study was to determine whether mental load during this task affected performance, sympathetic nervous system activity or pain in CRPS patients., Methods: We investigated twenty CRPS-I patients with pain in the upper extremity and twenty age- and sex-matched healthy controls. Each participant completed a limb recognition task. To experimentally manipulate mental load, the presentation time for each picture varied from 2 s (greatest mental load), 4, 6 to 10 s (least mental load). Before and after each run, pain intensity was assessed. Skin conductance was recorded continuously., Results: Patients with CRPS did not differ from controls in terms of limb recognition and skin conductance reactivity. However, patients with CRPS reported an increase in pain during the task, particularly during high mental load and during the latter stages of the task. Interestingly, state anxiety and depressive symptoms were also associated with increases in pain intensity during high mental load., Conclusions: These findings indicate that high mental load intensifies pain in CRPS. The increase of pain in association with anxiety and depression indicates a detrimental effect of negative affective states in situations of high stress and mental load in CRPS., Significance: The effects of mental load need to be considered when patients with CRPS-I are investigated for diagnostic or therapeutic reasons., (© 2018 European Pain Federation - EFIC®.)

Faced with a patient who presents with unexplained disproportionate pain, a surgeon may be tempted to diagnose a low pain threshold, malingering, poor coping, anxiety, or other emotional condition. However, a variety of conditions must be ruled out before the orthopedist can prescribe watchful waiting. Computed tomography and magnetic resonance imaging can detect occult fractures, acute spinal conditions or vascular occlusions, but early on are inadequate to diagnose a compartment syndrome, necrotizing fasciitis, or reflex sympathetic dystrophy (RSD). These diagnoses underpin a pain-out-of-proportion situation whereby the patient presents with disproportionate pain following a sometimes minor trauma with normal imaging studies and otherwise nonspecific presentations. Though these conditions are well described in the literature, investigations of malpractice data reveal a non-negligible prevalence of missed diagnoses for each of these entities. Determining that a patient exhibits otherwise unexplained pain-out-of-proportion situation is the first step in making a timely diagnosis.

A 36-year-old woman sustained a Grade 2 ankle sprain at work. Two days after the injury, the ankle and foot became red and she complained of "intense burning pain." First diagnosed with complex reflex sympathetic dystrophy, the employee was prescribed medications that provided some pain relief; a subsequent temporary nerve block provided additional relief. However, the symptoms returned and she was treated unsuccessfully with surgical sympathectomy. The employee was referred to a neurologist and diagnosed with primary erythromelalgia, a rare pain disorder that can be mistaken as complex reflex sympathetic dystrophy.

Background: The timing of diagnosis of complex regional pain syndrome (CRPS) 1 remains a challenge due to the large heterogeneity of clinical presentations. We describe the distribution and differences in outcomes and clinical manifestations between time points and patient groups with and without CRPS 1 following an initiating event., Methods: Prospective cohort study with a consecutive registration of patients presenting with painful swelling of the affected extremity after an initiating event and follow-up visits after 3, 6 and 12 months., Results: Forty-two patients were enrolled (37 females, mean age 55.1 years). At baseline, 35 participants (83%, females n = 30) fulfilled the diagnostic criteria for CRPS 1. At 3 months, 19 out of the initial 35 CRPS 1 patients (54%) did not meet the diagnostic criteria anymore. Besides our inclusion criteria of a painful swelling, early manifestations indicating a CRPS 1 primarily include an impaired quality of life (SF-35, EQ5-D), more pain (NRS, MPQ) and restricted range of motion., Conclusions: CRPS 1 develops within 8 weeks following a noxious event. Although many CRPS 1 patients reach partial remission within the first 3 months, signs and symptoms do not improve significantly at 1 year. In order to identify prognostic risk factors large prospective cohort studies are needed., Significance: This prospective cohort study follows patients with complaints most suspected for complex regional pain syndrome (CRPS) 1. CRPS 1 develops within 8 weeks following a noxious event. Although many CRPS 1 patients reach partial remission within the 3 months, symptoms do not improve significantly at 1 year., (© 2017 European Pain Federation - EFIC®.)

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.

Type 1 complex regional painful syndrome (CRPS-1) has a complex physiopathology. The aim of this study was to evaluate the effectiveness of physical therapy under hypnotherapy to treat this condition. Twenty patients with CRPS-1 at the wrist and hand were evaluated retrospectively: 13 women and 7 men with an average age of 56 years (34-75). Thirteen patients were in the inflammatory phase and 7 in the dystrophic phase. The main endpoints were pain (VAS, analgesic use), stiffness (wrist and finger range of motion), and strength (pinch and grasp). Secondary endpoints were functional scores (QuickDASH, PWRE), patient satisfaction, return to work, and side effects. Results were satisfactory in all cases after 5.4 sessions on average. VAS decreased by 4 points, PWRE-pain by 4.1 points, and analgesic use was limited to paracetamol upon request. Finger and wrist range of motion increased and the QuickDASH decreased by 34 points, PRWE-function by 3.8 points, pinch strength increased 4 points, and grasp strength by 10 points. Return to work was possible in 80% of the cases. All patients were satisfied or very satisfied with the treatment. Physical therapy under hypnosis appears to be an effective treatment for CRPS-1 at the wrist and hand no matter the etiology., (Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) has a peculiar involvement pattern; clinically it is known as split hand syndrome and electrophysiologically shows abnormalities in the abductor pollicis brevis (APB)/abductor digiti minimi (ADM) ratio. The aim of this study was to find a significant electrophysiological parameter in upper limb onset ALS patients with normal APB/ADM ratio when compared to cervical spondylotic amyotrophy (CSA) and healthy controls. We retrospectively reviewed the electrophysiological results of 47 upper limb onset ALS and 42 CSA cases; 20 healthy individuals were included as controls. We included ALS and CSA patients with normal ADM/APB ratio (≥0.6, and ≤1.7), and the parameters of electrophysiological study were compared. The electrophysiological parameters of statistical significance among ALS, CSA and normal controls were: amplitude of median and ulnar nerves, the terminal latency of median nerve, F-wave latency of median and ulnar nerves, terminal latency ratio of ulnar/median nerves, and F-wave latency ratio of ulnar/median nerves (p < 0.05). Among these parameters, the terminal latency ratio of ulnar/median nerve and terminal latency of median nerve in ALS were significantly different with both of CSA and normal control (p < 0.006). The abnormality in the terminal latency of the median nerve can be partly explained by the distal motor axonal dysfunction due to sodium and potassium channel abnormalities. The hypothesis of distal axonopathy is known to play an important role in the pathogenesis of ALS causing a significant prolongation of the terminal latency in the median nerve and the ulnar/median nerve ratio.

Background: The question of hormonal dysregulation in patients with CRPS I in whole was investigated very scantily. There are only a few studies concerning catecholamines, oestrogens and endorphins independently. Other hormones were studied in patients with different other chronic pain conditions. Considering the accumulation of sufficient knowledge about the role of disadaptation processes in CRPS I pathogenesis and the role of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-ovarian systems in the process of adaptation it was logical and consistent to define the role of hormonal dysregulation of these systems in patients with CRPS I., Objectives: Our objective was to determine the role of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-ovarian systems in pathogenesis of complex regional pain syndrome type I (CRPS I) in women., Methods: We investigated the pituitary gonadotropic function and the function of sex glands in women with CRPS I and healthy volunteers by measuring the plasma levels of estradiol (E 2 ), follicle-stimulating hormone, luteinizing hormone, prolactin, adrenocorticotropic hormone, and cortisol, and urinary excretion of 17-ketosteroids, 17-oxycocorticosteroids, epinephrine and norepinephrine., Results: Women with CRPS I were characterized by the decreased content of oestrogens in the blood plasma and increased pituitary gonadotrophic function. The disturbed ratio of anabolic and catabolic steroids in women with CRPS I was detected due to lower adrenal cortex function., Conclusions: In patients with CRPS I endocrine status is characterized by hormonal imbalances of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems. The changes in reproductive and adaptation homeostasis characterize CRPS I as a form of the disease of disadaptation., Significance: This study determined the role of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-ovarian systems in pathogenesis of CRPS I., (© 2016 European Pain Federation - EFIC®.)

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.

Complex regional pain syndrome type 1 (CRPS-I) remains one of the most clinically challenging neuropathic pain syndromes and its mechanism has not been fully characterized. Cannabinoid receptor 2 (CB2) has emerged as a promising target for treating different neuropathic pain syndromes. In neuropathic pain models, activated microglia expressing CB2 receptors are seen in the spinal cord. Chemokine fractalkine receptor (CX3CR1) plays a substantial role in microglial activation and neuroinflammation. We hypothesized that a CB2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by regulating CB2 and CX3CR1 signaling. We used chronic post-ischemia pain (CPIP) as a model of CRPS-I. Rats in the CPIP group exhibited significant hyperemia and edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and licking). Intraperitoneal administration of MDA7 (a selective CB2 agonist) attenuated mechanical allodynia induced by CPIP. MDA7 treatment was found to interfere with early events in the CRPS-I neuroinflammatory response by suppressing peripheral edema, spinal microglial activation and expression of CX3CR1 and CB2 receptors on the microglia in the spinal cord. MDA7 also mitigated the loss of intraepidermal nerve fibers induced by CPIP. Neuroprotective effects of MDA7 were blocked by a CB2 antagonist, AM630. Our findings suggest that MDA7, a novel CB2 agonist, may offer an innovative therapeutic approach for treating neuropathic symptoms and neuroinflammatory responses induced by CRPS-I in the setting of ischemia and reperfusion injury., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

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.

Complex regional pain syndrome (CRPS) is characterized by continuous pain, disproportional to the initial trauma. It usually spreads to the distal parts of the affected limb. Besides continuing pain, a mix of sensory, sudo- and vasomotor disturbances, motor dysfunction, and trophic changes is responsible for physical complaints. Vasomotor disturbance is characterized by changes in skin temperature and color. In CRPS patients with a cold extremity, a decrease in blood flow can cause decreased tissue saturation and tissue acidosis, resulting in ischemic pain. The pathophysiology of vasomotor disturbances is not completely understood. Temperature asymmetry is generally assumed as a result of disturbance in the sympathetic nervous system. Vasodilating drugs and sympathetic blockade have been cornerstones of therapy in cold CRPS for years. However, only a limited part of these patients improve on this kind of therapies. Research has shown a pivotal role for inflammation in the pathophysiology of CRPS. Inflammation can result in endothelial dysfunction. Endothelial function plays an important role in the local regulation of vascular tone. Endothelial dysfunction could be another mechanism responsible for the vasomotor disturbances in cold CRPS. An important goal in the treatment of cold-type CRPS is the restoration of a normal blood flow. Consequently it is important to distinguish the underlying pathophysiological mechanisms of vasomotor disturbances. A disturbance of the sympathetic nervous system may require another type of treatment than inflammation-induced endothelial dysfunction. Diagnostic tools to distinguish these underlying pathophysiological mechanisms of vasomotor disturbances would enable a mechanism-based treatment and improve clinical outcome., (© 2015 World Institute of Pain.)

Objective: To investigate the effects of mirror therapy on upper limb motor functions, spasticity, and pain intensity in patients with hemiplegia accompanied by complex regional pain syndrome type 1., Design: Randomized controlled trial., Setting: Training and research hospital., Participants: Adult patients with first-time stroke and simultaneous complex regional pain syndrome type 1 of the upper extremity at the dystrophic stage (N=30)., Interventions: Both groups received a patient-specific conventional stroke rehabilitation program for 4 weeks, 5 d/wk, for 2 to 4 h/d. The mirror therapy group received an additional mirror therapy program for 30 min/d., Main Outcome Measures: We evaluated the scores of the Brunnstrom recovery stages of the arm and hand for motor recovery, wrist and hand subsections of the Fugl-Meyer Assessment (FMA) and motor items of the FIM-motor for functional status, Modified Ashworth Scale (MAS) for spasticity, and visual analog scale (VAS) for pain severity., Results: After 4 weeks of rehabilitation, both groups had significant improvements in the FIM-motor and VAS scores compared with baseline scores. However, the scores improved more in the mirror therapy group than the control group (P<.001 and P=.03, respectively). Besides, the patients in the mirror therapy arm showed significant improvement in the Brunnstrom recovery stages and FMA scores (P<.05). No significant difference was found for MAS scores., Conclusions: In patients with stroke and simultaneous complex regional pain syndrome type 1, addition of mirror therapy to a conventional stroke rehabilitation program provides more improvement in motor functions of the upper limb and pain perception than conventional therapy without mirror therapy., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Factors influencing disability and work absence in complex regional pain syndrome type-1 (CRPS)-1 have not been thoroughly described in the literature. We sought to determine whether demographic variables, work-related factors, CRPS clinical severity ratings, pain scores, or psychological variables were associated with disability and sick leave in early CRPS-1., Methods: A total of 66 CRPS-1 patients were recruited within 12 weeks of CRPS onset. Patients completed measures of pain, depression, anxiety, stress, pain catastrophizing, and pain-related fear. A physical examination was conducted to assess signs and symptoms of CRPS and to calculate a CRPS severity score. Demographic details, clinical details, treatments, work type, and work status were recorded., Results: In multivariate analyses, the following factors were associated with greater disability: higher pain scores, more restricted ankle or wrist extension, and higher levels of depression. Among the 49 who were either working or studying before developing CRPS, 28 had stopped work or study at the time of assessment. Multivariate analyses showed that sick leave was more likely among those whose CRPS was triggered by more severe injuries, whose work was more physically demanding, among those with higher disability scores, and there was also a significant effect of depression on sick leave, which was mediated by disability., Discussion: Although the study was cross-sectional and so cannot differentiate cause from effect, results suggest that even in the early stages of CRPS, a cycle of pain, disability, depression, and work absence can emerge. Treatments aimed to prevent this cycle may help prevent adverse long-term outcomes.

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.

Purpose: Cutaneous sympathetic pathophysiology in complex regional pain syndrome type 1 (CRPS-1) is not yet completely understood. To evaluate cutaneous sympathetic dysfunction in CRPS-1, we evaluated sympathetic sweat response (SSwR) and skin vasomotor reflex (SkVR) in CRPS-1 patients., Methods: We studied 10 CRPS-1 patients (age 41 ± 13 years; 5 females and 5 males; disease duration 20 ± 22 months) and 10 healthy subjects (age 44 ± 13 years; 3 females and 7 males). SkVRs and SSwRs to several sympathetic activating procedures were recorded on the palms of the CRPS-1 patients (affected side) and controls (right side)., Results: There were no significant differences in the baselines of sweat output and skin blood flow between the CRPS-1 and control groups. SSwR and SkVR amplitudes were significantly lower in the CRPS-1 group than in the control group. There was no significant correlation between disease duration and SSwR or SkVR amplitudes among the patients., Conclusions: The reduced SSwRs and SkVRs in the affected limb of our CRPS-1 patients may reflect underlying damage to the sympathetic postganglionic fibres.

Complex regional pain syndrome (CRPS) type I is characterized by somatosensory and motor deficits, and abnormalities have been reported for primary somatosensory (S1) and motor cortex (M1) excitability. For the latter, reduced short-latency intracortical inhibition (SICI) has been demonstrated in the somatotopic representation of the affected side. Recently, an intervention of applying anesthetic cream to the forearm has been shown to modulate both somatosensory deficits (eg, spatial tactile resolution [STR]) and SICI measured in hand muscles. We examined the efficacy of this intervention in patients with CRPS I. Cutaneous anesthesia of the forearm of the affected side was used to increase SICI of hand muscles and decrease impaired STR of the affected limb. In a double-blinded placebo-controlled study, we enrolled 12 patients with unilateral CRPS I of the hand in the chronic state. Before and after intervention, we measured motor evoked potentials of the first dorsal interosseus to obtain SICI and STR of both hand sides. Patients showed decreased STR on the tip of the thumb of their affected side, which improved after anesthetic cream but not after placebo application. Hand motor function of the affected side improved after anesthetic cream but not after placebo. Pain intensity was not modulated after intervention. At both hemispheres, SICI was decreased compared with reference values but selectively increased at the intervention side only after analgesic cream and not after placebo. Temporary deafferentation of an area neighbouring the CRPS-affected region can modulate neuropathological characteristics of CRPS and might be a promising strategy for therapeutic interventions.

Previous studies have shown that the outcomes of complex regional pain syndrome (CRPS) vary significantly between patients, but few studies have identified prognostic indicators. The aim of this study was to determine whether psychological factors are associated with recovery from recently onset CRPS amongst patients followed prospectively for 1 year. Sixty-six patients with CRPS (type 1) were recruited within 12 weeks of symptom onset and assessed immediately and at 6 and 12 months, during which time they received treatment as usual. At each assessment, the following were measured: signs and symptoms of CRPS, pain, disability, depression, anxiety, stress, pain-related fear, pain catastrophising, laterality task performance, body perception disturbance, and perceived ownership of the limb. Mixed-effects models for repeated measures were conducted to identify baseline variables associated with CRPS severity, pain, and disability over the 12 months. Results showed that scores for all 3 outcome variables improved over the study period. Males and those with lower levels of baseline pain and disability experienced the lowest CRPS severity scores over 12 months. Those with lower baseline anxiety and disability had the lowest pain intensity over the study period, and those with lower baseline pain and pain-related fear experienced the least disability over the 12 months. This suggests that anxiety, pain-related fear, and disability are associated with poorer outcomes in CRPS and could be considered as target variables for early treatment. The findings support the theory that CRPS represents an aberrant protective response to perceived threat of tissue injury.

We have recently demonstrated a role of the vascular endothelium in peripheral pain mechanism by disrupting endothelial cell function using intravascular administration of octoxynol-9, a non-selective membrane active agent. As an independent test of the role of endothelial cells in pain mechanisms, we evaluated the effect of homocysteine, an agent that damages endothelial cell function. Mechanical stimulus-induced enhancement of endothelin-1 hyperalgesia in the gastrocnemius muscle of the rat was first prevented then enhanced by intravenous administration of homocysteine, but was only inhibited by its precursor, methionine. Both homocysteine and methionine significantly attenuated mechanical hyperalgesia in two models of ergonomic muscle pain, induced by exposure to vibration, and by eccentric exercise, and cutaneous mechanical hyperalgesia in an ischemia-reperfusion injury model of Complex Regional Pain Syndrome type I, all previously shown responsive to octoxynol-9. This study provides independent support for a role of the endothelial cell in pain syndromes thought to have a vascular basis, and suggests that substances that are endothelial cell toxins can enhance vascular pain., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

Complex regional pain syndrome (CRPS) is a very complicated chronic pain disorder that has been classified into two types (I and II). Endothelin (ET) receptors are involved in pain conditions at the spinal level. We investigated the role of spinal ET receptors in CRPS. Chronic post-ischemia pain (CPIP) was induced in male Sprague-Dawley rats as a model for CRPS-I by placing a tourniquet (O-ring) at the ankle joint for 3h, and removing it to allow reperfusion. Ligation of L5 and L6 spinal nerves to induce neuropathic pain was performed as a model for CRPS-II. After O-ring application and spinal nerve ligation, the paw withdrawal threshold was significantly decreased at injured sites. Intrathecal administration of the selective ET-B receptor antagonist BQ 788 dose-dependently increased the withdrawal threshold in both CRPS-I and CRPS-II. In contrast, ET-A receptor antagonist BQ 123 did not affect the withdrawal threshold in either CRPS type. The ET-1 levels of plasma and spinal cord increased in both CRPS types. Intrathecal BQ 788 decreased the spinal ET-1 level. These results suggest that ET-1 is involved in the development of mechanical allodynia in CRPS. Furthermore, the ET-B receptor appears to be involved in spinal cord-related CRPS., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The etiology of shoulder-hand syndrome is as yet unknown. We hypothesized that it may be due to damaged unmyelinated fibers in front of the subscapular muscle. We examined the existence of edema and hypersensitivity to pain in the hands of stroke patients during the subacute stage and their relationships to cutaneous temperatures of the index fingertips in 75 hemiplegic patients (23 without edema, 32 with only edema, and 20 with edema plus allodynia). Patients were placed into two groups (comfortable and warm) depending on room temperature (22.2-25.6°C and 25.7-30°C, respectively). Of the patients with hand edema plus allodynia, 75% had a large lesion in the capsula, cortical white matter, and putamen. It was previously reported that the cutaneous temperature of the arm on the paralysis side of patients with lesions of the capsula or putamen was lower than that on the non-paralysis side. In the edema plus allodynia group, the temperature of the index fingertip on the affected side was higher than that of their contralateral fingers; the differences were smaller under warm conditions possibly due to blockade of the sympathetic nerves in the peripheral nerve. By contrast, in patients in the edema group, there were no differences in cutaneous temperatures of their two index fingers. Thus, it appears that patients with mild cases of shoulder-hand syndrome have conduction blocks in the posterior cord of the brachial plexus, while those with severe cases have both conduction blocks and neurogenic inflammation in both the lateral and posterior cords.

Purpose: Wrist fracture is considered a typical initiating trauma for complex regional pain syndrome type I (CRPS I). However, few studies have comprehensively evaluated factors associated with the occurrence of CRPS I after the surgical treatment of a distal radius fracture (DRF). This study evaluates the factors influencing the occurrence of CRPS I after the surgical treatment of a DRF., Methods: A total of 477 patients with a DRF who had been treated surgically were enrolled in this prospective observational study. Patients were followed for 6 months after surgery, and CRPS I was diagnosed using the Budapest diagnostic criteria for research. The factors assessed for the development of CPRS I were age, gender, the body mass index, the type of fracture, the energy of trauma, the number of trial reductions, the type of surgery, and the duration of immobilization. A multivariate logistic regression analysis was conducted to identify independent predictors of the occurrence of CRPS I., Results: Among the 477 patients, 42 (8.8 %) satisfied the Budapest criteria for CRPS I within 6 months of surgery. Female patients developed CRPS I more frequently, and the patients who developed CRPS I were older and more likely to sustain a high energy injury or have a comminuted fracture. According to the multivariate analysis, female patients and those with a high energy trauma or severe fracture type were significantly more likely to develop CRPS I (p = 0.02, 0.01, and 0.01, respectively)., Conclusions: High energy injuries, severe fractures, and the female gender contribute to the development of CRPS I after the surgical treatment of DRF. The results have important implications for physicians who wish to identify patients at high risk for CRPS I after operative fixation for DRF and instigate treatment accordingly.

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: In posttraumatic dystrophy the resorption of cancellous bone remains an unsolved phenomenon., Objectives: The possible effects of arteriovenous (av) anastomoses, hypoxia and acidosis in posttraumatic dystrophy on cancellous bone structures should be elucidated., Material and Methods: In posttraumatic dystrophy of the hand after distal radius fracture, hand fractures and elective hand surgery [20] the results suggest that persistent av anastomoses could be the reason for this syndrome. Possible pathways for the occurrence of cancellous bone resorption are discussed in context with the literature., Results and Conclusion: Intraosseous av anastomoses with acidosis and hypoxia of the tissues are probably responsible for the excessive activity of osteoclasts in acute posttraumatic dystrophy. Even enhancements in the late static phase of the three phase bone scan (TPBS) are in agreement with this hypothesis. In cancellous bone these enhancements are induced by the bone seeking tracers. The nomenclature for these tracer molecules is in line with the recommendations of International Union of Pure and Applied Chemistry (IUPAC) as methylene bisphosphonate and hydroxymethylene bisphosphonate. From this, therapeutic recommendations for posttraumatic dystrophy can be derived. The term diphosphonates should be changed to bisphosphonates.

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.

Purpose: Deep tissue hypoxia has been hypothesized in the pathogenesis of complex regional pain syndrome type 1 (CRPS 1) for some patients. The purpose of this study was to determine if near-infrared spectroscopy (NIRS) could detect differences in deep tissue oxygen saturation (StO2) and microcirculatory function in the hands of patients with CRPS 1., Methods: Tissue oxygen saturation was evaluated at baseline and during an ischemia reperfusion challenge using vascular occlusion testing (VOT) in affected vs unaffected hands of patients with unilateral upper limb CRPS 1. A non-randomized experimental study design was used with baseline StO2 as the primary outcome measure. Secondary outcome measures were occlusion and reperfusion slopes from VOT. Values were compared with the unaffected, contralateral hand and with the dominant and non-dominant hands of sex and age-matched volunteers. Correlations between values derived from NIRS and measures of pain and function from the Brief Pain Inventory (BPI) and the Disability of the Arm, Shoulder and Hand (DASH) questionnaires were explored., Results: Independent of handedness, the baseline StO2 of the affected hands of ten CRPS 1 patients was significantly lower than that of their unaffected hands (-5.8%; 95% confidence interval [CI] -10.6 to -1.0; P = 0.02). The baseline StO2 of affected CRPS 1 hands was also significantly lower than the non-dominant hands of ten volunteers (-7.3%; 95% CI -12.4 to -2.3; P = 0.007). Differences in VOT occlusion and reperfusion slopes did not reveal changes that could be uniquely attributed to CRPS 1. No significant correlations were detected between values derived from VOT and values for pain and function obtained from BPI and DASH questionnaires for patients with CRPS 1., Conclusions: Hands of patients affected by CRPS 1 of the upper limb showed significantly lower StO2 compared with their unaffected contralateral hand as well as the hands of control subjects. This trial was registered at: ClinicalTrials.gov: NCT01586377.

Objective: To examine the incidence and predictors of complex regional pain syndrome type I (CRPS I) after fracture of the distal radius., Design: Prospective study., Setting: University hospital., Participants: A consecutive sample of patients (N=90) with fracture of the distal radius treated by closed reduction and casting., Interventions: Not applicable., Main Outcome Measures: Occurrence of CRPS I, occurrence of pain, wrist and hand range of motion, radiographic measures, Patient-Rated Wrist Evaluation, Hospital Anxiety and Depression Scale, and Medical Outcomes Study 36-Item Short-Form Health Survey at baseline and 1, 3, 6, and 9 months follow-up., Results: CRPS I occurred in 29 patients (32.2%) with a mean delay ± SD of 21.7±23.7 days from cast removal. Univariate analyses found significant differences between patients with CRPS I and patients without CRPS I at baseline for sex (P=.021), socioeconomic level (P=.023), type of trauma (P=.05), pain at rest and activity (P=.006 and P<.001, respectively), wrist dorsiflexion and pronation (P=.002 and P=.001, respectively), finger flexion (P=.047), thumb opposition (P=.002), function of the hand (P<.001), and physical quality of life (QOL) (P=.013). Logistic regression showed that risk for CRPS I was higher in cases of women (odds ratio [OR]=5.774; 95% confidence interval [CI], 1.391-23.966), medium and low energy trauma patients (OR=7.718; 95% CI, 1.136-52.44), patients with a Medical Outcomes Study 36-Item Short-Form Health Survey physical functioning score <40 (OR=4.931; 95% CI, 1.428-17.025), and patients with Patient-Rated Wrist Evaluation pain subscale score >16 (OR=12.192; 95% CI, 4.484-43.478)., Conclusions: CRPS I occurs frequently during the third and fourth week after cast removal, especially in women who report severe pain and impairment of physical QOL. Additional prospective studies are required to verify these findings in comminuted and operated fractures of the distal radius., (Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)