Alpha-lipoic acid reduces nociception by reducing oxidative stress and neuroinflammation in a model of complex regional pain syndrome type I in mice.

Complex regional pain syndrome type I (CRPS-I) is a disabling pain condition without adequate treatment. Chronic post-ischemia pain injury (CPIP) is a model of CRPS-I that causes allodynia, spontaneous pain, inflammation, vascular injury, and oxidative stress formation. Antioxidants, such as alpha lipoic acid (ALA), have shown a therapeutic potential for CRPS-I pain control. Thus, we aim to evaluate if ALA repeated treatment modulates neuroinflammation in a model of CRPS-I in mice. We used male C57BL/6 mice to induce the CPIP model (O-ring torniquet for 2 h in the hindlimb). For the treatment with ALA or vehicle (Veh) mice were randomly separated in four groups and received 100 mg/kg orally once daily for 15 days (CPIP-ALA, CPIP-Veh, Control-ALA, and Control-Veh). We evaluated different behavioral tests including von Frey (mechanical stimulus), acetone (cold thermal stimulus), rotarod, open field, hind paw edema determination, and nest-building (spontaneous pain behavior). Also, hydrogen peroxide (H2O2) levels, NADPH oxidase and superoxide dismutase (SOD) activity in the sciatic nerve and spinal cord, and Iba1, Nrf2, and Gfap in spinal cord were evaluated at 16 days after CPIP or sham induction. Repeated ALA treatment reduced CPIP-induced mechanical and cold allodynia and restored nest-building capacity without causing locomotor or body weight alteration. ALA treatment reduced SOD and NADPH oxidase activity, and H2O2 production in the spinal cord and sciatic nerve. CPIP-induced neuroinflammation in the spinal cord was associated with astrocyte activation and elevated Nfr2, which were reduced by ALA. ALA repeated treatment prevents nociception by reducing oxidative stress and neuroinflammation in a model of CRPS-I in mice.

Prednisolone 20 mg vs 40 mg in complex regional pain syndrome type I: A randomized controlled trial.

BACKGROUND: High dose of corticosteroid has been found beneficial in complex regional pain syndrome type I (CRPS-I). We report the efficacy and safety of prednisolone 20 mg versus 40 mg in CRPS-I in an open label randomized controlled trial. METHODS: The patients with CRPS-I of the shoulder joint with a CRPS score of ≥8 were included. Their demographic details, comorbidities, and underlying etiology were noted. The severity of CRPS was assessed using a 0-14 CRPS scale, the pain using a 0-10 Visual Analogue Scale (VAS), and sleep quality using a 0-10. Daily Sleep Interference Scale (DSIS). Patients were randomized to prednisolone 40 mg/day (group I) or 20 mg/day (group II) for 14 days, then tapered to 10 mg in group I and to 5 mg in group II by 1 month. Thereafter both groups received prednisolone 5 mg/day for 2 months. The primary outcome was a >50% reduction in VAS score, and secondary outcomes were a reduction in CRPS score, DSIS score, and adverse events. RESULTS: Fifty patients were included, and their baseline characteristics were comparable. At one month, all the patients had >50% reduction in the VAS score. The effect size was 0.38 (95% CI 0.93-0.20; p = 0.20). On the Kaplan-Mayer analysis, the improvement in the VAS score (Hazard ratio-1.43, 95 % CI-0.80-2.56, p = 0.22) and the CRPS score (HR-0.79,95 % CI-0.45-1.39; p = 0.41) was insignificant between the two groups. The DSIS score improved in group II (HR-1.85,95 % Cl-1.04-3.31,p = 0.04). Group I patients needed frequent adjustment of antidiabetic drugs (14 vs 6; p = 0.04). CONCLUSION: The efficacy of prednisolone 20 mg is not inferior to 40 mg in CRPS-I, and is safe in diabetic patients. LIMITATIONS: This is an open label randomized controlled trial with small sample size without a placebo arm.

Harmful or safe? Exposure and pain provocation during physiotherapy of complex regional pain syndrome I: a narrative review.

BACKGROUND: Complex regional pain syndrome (CRPS) is a clinical diagnosis and an umbrella term for a heterogeneous group of states associated with pain disproportionate to any inciting event, together with a number of signs and symptoms that are manifested mainly in the limbs. There are often concerns among clinicians and patients about the potential harms caused by pain provocation during physiotherapy of CRPS, even though clinical guidelines de-emphasize pain-contingency. OBJECTIVE: The objective of this narrative review is to summarize current evidence regarding potential harms due to pain provocation during so-called exposure-based therapies in individuals with CRPS. METHODS: Six studies evaluating exposure-based approach were included (n= 6). RESULTS: Although only one included study focused primarily on safety and in the rest of the included studies the reporting of harms was insufficient and therefore our certainty in evidence is very low, taken together with outcome measures, available data does not point to any long-term deterioration in symptoms or function, or any major harms associated with pain provocation during physiotherapy of CRPS. CONCLUSION: There is a great need for higher-quality studies to determine which therapeutic approach is the most appropriate for whom and to evaluate the risks and benefits of different approaches in more detail.

Combining Stellate ganglion block and intravenous regional anesthesia to treat complex regional pain syndrome: A 19-years' experience in a tertiary center.

OBJECTIVES: To study reduction in pain score after treatment with intravenous regional anesthesia (IVRA) and Stellate ganglion block (SGB) combination on complex regional pain syndrome (CPRS) patients and to quantify patients' satisfaction with treatment and occurrence of complications. METHODS: This is a record-based retrospective review carried out in 2020, targeting patients treated in the University of Jordan Hospital, Amman, Jordan, over the years 2002-2020. RESULTS: Among 99 patients, a significant drop in pain scores occurred in 88% of the patients' sample. Gender, age, type of CRPS, and duration of symptoms didn't affect statistical results. An average of 8.6 sessions needed to achieve 50% drop in pain score, and 2-3 sessions for first clinical improvement. Patients with previous application of plaster of Paris had increased success rates. CONCLUSION: We find it practical, inexpensive, safe, and straightforward to combine SGB with IVRA for CRPS patients.

Effectiveness of prednisolone in complex regional pain syndrome treatment: A systematic narrative review.

BACKGROUND: Many patients with complex regional pain syndrome (CRPS) experience refractory pain with severe restrictions in the activities of daily living. Oral prednisolone is commonly used to treat these patients. PURPOSE: To review previous studies assessing the effects of prednisolone in CRPS patients. METHODS AND MATERIALS: Articles published from January 1, 1980 to July 23, 2021 in the PubMed database were searched using the following key phrases: (prednisolone OR corticosteroid OR steroid) AND (complex regional pain syndrome OR reflex sympathetic dystrophy OR shoulder-hand syndrome OR causalgia). Specifically, we included those articles in which oral prednisolone or corticosteroids were used to control the CRPS symptoms. RESULTS: In total, 11 articles were included, comprising 3 randomized trials, 5 single-arm prospective observational studies, and 3 retrospective studies. Nearly all previous studies reported that oral prednisolone can effectively control the CRPS symptoms. Moreover, though 30-100 mg/day of oral prednisolone was initially administered in these studies, 30 mg/day was also found to be effective in controlling the symptoms. Although prednisolone was usually administered for 1-3 months, short-term treatment for 1-2 weeks was also reportedly effective. Furthermore, only 0%-30% of the patients in these studies had minor side effects after prednisolone treatment. CONCLUSIONS: Our review showed that prednisolone may be effective in alleviating the CRPS symptoms. To determine higher levels of evidence, a full systematic review with more highly qualified studies, such as randomized controlled trials, should be conducted in the future.

Involvement of nuclear factor κB and descending pain pathways in the anti-hyperalgesic effect of ß-citronellol, a food ingredient, complexed in ß-cyclodextrin in a model of complex regional pain syndrome - Type 1.

Complex regional pain syndrome type 1 (CRPS-1) is a painful syndrome without effective treatment. In order to explore possible new treatments, we used an animal model of CRPS-1 to examine the effects of ß-Citronellol (ßCT), a monoterpene found in a variety of plants that has been shown to have analgesic effects. We aimed to assess its effects alone, and complexed with ß-cyclodextrin (ßCD), which has been previously used to enhance the effects of a number of medicines. The ßCT-ßCD was characterized physiochemically using high performance liquid chromatography (HPLC) and differential scanning calorimetry (DSC) and shown to have 80% efficiency. In the animal model, Swiss mice were treated with ßCT, ßCT-ßCD, vehicle, pregabalin or sham and evaluated for hyperalgesia and motor coordination. Inflammatory mediators were measured by Western blot or ELISA and the descending pain pathway by immunofluorescence. ßCT was shown to have an anti-hyperalgesic effect (without affecting motor coordination) that reduced inflammatory mediators and activated the descending pain pathway, and these effects were increased with complexation in ßCD. Our results showed ßCT-ßCD to be a promising treatment for CRPS-1.

Clinical Study of Qingpeng Ointment Treating Shoulder-hand Syndrome After Cerebral Hemorrhage During the Rehabilitation Period.

BACKGROUND: Shoulder-hand syndrome (SHS) refers to a syndrome causing sudden edema, shoulder pain and limited hand function. Qingpeng ointment, a kind of Tibetan medicine, can reduce swelling, relieve pain, tonify stagnation and clear the meridians, which is consistent with the pathological mechanism of SHS after stroke. Therefore, if clinical trials can be used to explore the effectiveness of Qingpeng ointment for the treatment of poststroke SHS and promote its application in clinical medicine, it may prove the specific significance for the treatment of poststroke SHS poststroke SHS. OBJECTIVE: The aim of the study was to investigate the clinical efficacy and safety of Qingpeng ointment in the treatment of poststroke SHS and to provide an objective basis for a better therapeutic treatment for poststroke SHS. METHODS: A prospective, randomized, controlled study was conducted. This study recruited 120 patients with poststroke SHS who met the inclusion criteria. They were randomized into the treatment group and the control group, with 60 patients allocated to each group. The treatment group received routine medical treatment and rehabilitative care after using the Qingpeng ointment, while the patients in the control group received only routine treatment without the ointment. All patients received clinical assessment with the Visual Analogue Scale (VAS), measurement of the range of motion (ROM) of the upper-limb joints, the Fugl-Meyer Assessment of Upper Extremity (FMA-U) and the Modified Barthel Index Score (MBI) before and after the whole treatment. RESULTS: After 4 weeks of treatment, the VAS scores of both the groups decreased significantly (P ＜0.05), and the difference between the two groups was statistically significant (P < 0.05). No statistical significance was observed for the difference between the treatment group and control group in terms of the FMA-U and MBI scores and the forward bend, backward, outstretch, external rotation and pronation angles after treatment. The increases in the values of VAS, FMA-M and MBI in the treatment group were greater than those in the control group, and the difference was statistically significant (P < 0.05). The increases in the values of the forward bend, outreach and external rotation angles in the treatment group were greater than those in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: The treatment group showed better results than the control group in terms of the relief of pain symptoms, the improvement of motor function and the improvement of the activities of daily living for patients with shoulder-hand syndrome after cerebral hemorrhage. Qingpeng ointment was found to be effective and safe for treating poststroke SHS.

Ketamine and Cognitive Behavioral Therapy for Rapid Opioid Tapering With Sustained Opioid Abstinence: A Case Report and 1-Year Follow-up.

BACKGROUND: Ketamine, a potent analgesic and N-methyl-D-aspartate-(NMDA)-receptor antagonist, improves analgesic outcomes in patients with complex regional pain syndrome (CRPS). The NMDA receptor has also been implicated in opioid withdrawal. The use of ketamine to assist with a rapid opioid taper in the setting of CRPS has not been previously described. CASE: We present a case in which a 5-day continuous ketamine infusion was utilized in a robust multimodal analgesia regimen in combination with cognitive behavioral therapy (CBT) to successfully taper a patient with complex regional pain syndrome (CRPS) who was taking 330 mg of daily morphine equivalents completely off of opioids, minimize withdrawal symptoms, and produce sustained results. DISCUSSION: CRPS may involve catecholamine hypersensitivity and central sensitization and can be notoriously challenging to treat by itself even outside of the context of an opioid taper. The patient we describe here received one additional 5-day infusion at 6 months and remained opioid-free while experiencing a major improvement in function and lifestyle that he still maintains. This was possible through a combination of aggressive inpatient management with ketamine as the centerpiece, followed by consistent outpatient CBT to maintain results without the need for a return to opioids. This combination has previously not been described in the setting of a rapid opioid taper and this patient's underlying CRPS made it all the more remarkable.

Efectos del tratamiento multimodal en pacientes con síndrome de dolor regional complejo tipo 1 con, al menos, seis meses de evolución: un estudio descriptivo / Effects of multimodal treatment in patients with complex regional pain syndrome type 1 with, at least, 6 months of evolution: a descriptive study

Objetivos: El objetivo principal del presente trabajo es describir los cambios en el dolor posterior a esquema de tratamiento multimodal en pacientes con síndrome de dolor regional complejo tipo 1 (SDRC 1), con más de seis meses de evolución, que ingresan a control en Servicio de Medicina Física y Rehabilitación del Hospital Clínico San Borja Arriarán. Material y método: Series de casos de pacientes con sospecha o diagnóstico de SDRC 1 que ingresan para manejo a la Unidad de Dolor Crónico no Oncológico (UCDNO), a los se les realizaron evaluaciones de dolor a través de la Escala Visual Analógica (EVA) y del Cuestionario para la Graduación del Dolor Crónico, funcionalidad de la extremidad superior (EESS) con Quick DASH y la Escala Funcional de la Extremidad Inferior (Lower Extremity Functional Scale [LEFS]) para extremidades inferiores (EEII), al momento del ingreso y en seguimiento a los dos meses de manejo multimodal por equipo interdisciplinario. Resultados: La muestra se compuso de 14 pacientes: 6 tuvieron compromiso de EESS y 8 de EEII, en mayor porcentaje fue de mujeres, con un tiempo promedio para el diagnóstico de 14,6 meses y tiempo promedio de evolución al momento del ingreso de 19,8 meses. Posterior al tratamiento la EVA mostró una disminución estadística y clínicamente significativa (2,2 cm con una DS de 2,1 [p = 0,0018]). La variable Quick DASH mostró una reducción de 20,5 puntos con una DS de 20,2 (p = 0,0558) y la variable LEFS un incremento de 13,9 puntos con una DS de 20,8 (p = 0,1008), ambas diferencias no son estadísticamente significativas pero ambas con diferencias clínicas mínimamente importantes relevantes. Se demostró correlación moderada pero que no es estadísticamente significativa entre el tiempo de evolución y la intensidad del dolor que presentan los pacientes al momento de la primera evaluación. Conclusiones: Las intervenciones multimodales guiadas por Fisiatra en un equipo interdisciplinario en el manejo del SDRC permitieron demostrar, después de un periodo de seguimiento, cambios clínicamente significativos en disminución del dolor y mejoría en funcionalidad, con disminución también en aspectos de discapacidad asociada

Objectives: The main objective of this work is to describe the changes in pain after a multimodal treatment scheme in patients with Complex Regional Pain Syndrome type 1 (CRPS 1), with more than 6 months of evolution, who enter treatment at the Physical Medicine and Rehabilitation Service of the San Borja Arriarán Clinical Hospital. Material and method: Series of cases of patients with suspicion or diagnosis of CRPS 1 who were admitted for management to the Non-Oncological Chronic Pain Unit, who underwent pain assessments through the Visual Analogue Scale (VAS) and the Chronic Pain Grade Questionnaire, functionality of the upper extremity (UE) with Quick DASH and the Lower Extremity Functional Scale Functional Scale for lower extremities (LE), at the time of admission and in follow-up after two months of multimodal management by an interdisciplinary team. Results: The sample consisted of 14 patients, 6 had a compromise of UE and 8 of LE, in a greater percentage of women, with an average time for the diagnosis of 14.6 months and average time of evolution at the time of admission of 19.8 months. After the treatment, the VAS showed a statistically and clinically significant decrease (2.2 cm with a DS of 2.1 [p = 0.0018]). The variable Quick DASH showed a reduction of 20.5 points with a DS of 20.2 (p = 0.0558) and the variable LEFS an increase of 13.9 points with a DS of 20.8 (p = 0.1008), both differences are not statistically significant but both with Minimal Clinically Important Difference relevant. Moderate correlation was demonstrated but it is not statistically significant between the time of evolution and the intensity of the pain presented by the patients prior to the start of the multimodal treatment. Conclusions: The multimodal interventions guided by Physiatrist in an interdisciplinary team in the management of the CRPS allowed to demonstrate, after a period of follow-up, clinically significant changes in pain reduction and improvement in functionality, with a decrease also in aspects of associated disability

Bisphosphonates in the treatment of complex regional pain syndrome: is bone the main player at early stage of the disease?

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.

Extrapyramidal signs occurring after sympathetic block for complex regional pain syndrome responding to diphenhydramine: Two case reports.

RATIONALE: To present an unusual extrapyramidal motor response occurring after a sympathetic block in CRPS and its successful treatment with diphenhydramine. PATIENT CONCERNS: Severe pain related to Complex Regional Pain Syndrome type 1 interfering with activities of daily living. DIAGNOSES: Complex Regional Pain Syndrome type 1. INTERVENTIONS: We report a video case reports of two patients with a diagnosis of CRPS type-I. Both patients exhibited similar presentation of unusual extrapyramidal motor response of the affected limb following lumbar sympathetic block. Both patients were treated with intravenous diphenhydramine to abort the extrapyramidal motor response. OUTCOMES: Both patients similarly responded to treatment with intravenous diphenhydramine with abrupt resolution of the motor response. LESSONS: Sympathetic blockade may interfere with the adaptive autonomic reflex circuits of the motor balance homeostasis in patients with complex regional pain syndrome. Disinhibition of extrapyramidal system may lead to immediate expression of extrapyramidal signs following the sympathetic block. Diphenhydramine, with its anti-histaminic and anticholinergic properties, may be effective in aborting such extrapyramidal signs, and should be considered as a treatment option in similar cases.

Complex regional pain syndrome type 1 in the medico-legal setting: High rates of somatoform disorders, opiate use and diagnostic uncertainty.

Objective The aim of this study was to review demographic and clinical characteristics of patients with complex regional pain syndrome type 1 (CRPS) seen in a UK medico-legal setting - particularly the relationship between CRPS and somatoform disorders. Methods Fifty consecutive cases of CRPS (interviewed 2005-2016) undergoing psychiatric assessment were reviewed. A systematic assessment of mental states was conducted via interview and examination of medical/psychiatric records. Thirty patients also completed the Brief Illness Perception Questionnaire (BIPQ). Results Sixty per cent of patients ( n = 30) were female, and the mean age was 43 years. Twenty-two per cent ( n = 11) were employed, and 60% ( n = 30) received disability benefits. Symptoms were reported in the upper limb (62%; n = 31), lower limb (30%; n = 15), both (6%; n = 3) or elsewhere (2%; n = 1). Eighty-four per cent ( n = 42) satisfied DSM-5 criteria for current somatoform disorder. A history of more than two pain-related functional somatic syndromes (e.g. non-cardiac chest pain) was found in 42% ( n = 21) and functional neurological symptoms (e.g. 'claw-hand') in 42% ( n = 21). BIPQ scores resembled those associated with somatoform disorders and disorders mediated by psychological factors (e.g. irritable bowel syndrome). In 38% ( n = 19), the CRPS diagnosis was disputed among experts. A history of depression was noted in 60% ( n = 30), panic attacks in 20% ( n = 10) and alcohol/substance misuse in 18% ( n = 9). Opiates were prescribed to 64% ( n = 32). Conclusions Patients diagnosed with CRPS involved in litigation have high rates of prior psychopathology (mainly somatoform disorders) and pain-related disability for which opiate use is common. They risk an adverse reaction to limb pain 'shaped' by maladaptive illness beliefs. The CRPS diagnosis lacks reliability in medico-legal settings and may cause iatrogenic harm.

Bisphosphonates for treatment of Complex Regional Pain Syndrome type 1: A systematic literature review and meta-analysis of randomized controlled trials versus placebo.

OBJECTIVES: Complex Regional Pain Syndrome Type 1 is a severely disabling pain syndrome with no definite established treatment. We have performed a systematic literature review and meta-analysis of all randomized controlled trials to assess the benefit of bisphosphonates on pain and function in patients with Complex Regional Pain Syndrome Type 1. METHODS: A systematic literature search was performed in the Medline, Embase and Cochrane databases. Two authors selected independently blinded randomized trials comparing bisphosphonates to placebo on short-term (J30 to J40) and medium term pain (M2-M3), safety and function in patients with CRPS 1. The methodological quality of the studies was analyzed. Data were aggregated using the method of the inverse of the variance. RESULTS: 258 articles were identified. Four trials of moderate to good quality comprising 181 patients (90 in the bisphosphonate group and 91 in the placebo group) were included in this meta-analysis. Short-term pain Visual Analog Scale was significantly lower in the bisphosphonate group versus the placebo group (SMD=-2.6, 95%CI [-1.8, -3.4], P<0.001), as well as the medium term Visual Analog Scale pain (SMD=-2.5, 95%CI [-1.4, -3.6], P<0.001). There were more adverse events in the bisphosphonate group (35.5%) than in the placebo group (16.4%) with a relative risk of 2.1 (95%CI [1.3, 3.5], P=0.004) and a number needed to harm of 4.6, (95%CI [2.4, 168.0]) but no serious side effects. CONCLUSIONS: Our results suggest that bisphosphonates reduce pain in patients with Complex Regional Pain Syndrome type 1. Other studies are needed to determine their effectiveness.

Síndrome doloroso regional complejo tipo 1. Análisis de 108 pacientes / Complex regional pain syndrome type 1: analysis of 108 patients

Introducción. El síndrome doloroso regional complejo (SDRC) tipo 1 se caracteriza por la presencia de dolor, edema, impotencia funcional, limitación de la movilidad, cambios tróficos, inestabilidad vasomotora y desmineralización ósea. Material y métodos. Se realizó un estudio observacional, descriptivo, retrospectivo y prospectivo de 108 pacientes de más de 18 años de edad, con sospecha clínica de SDRC, que cumplieran criterios de Doury. Se registraron datos demográficos, características clínicas, comorbilidades, antecedentes predisponentes y factores desencadenantes como traumatismo o fractura. Se evaluaron datos de laboratorio, radiografía simple comparativa, gammagrafía ósea en 3 fases con tecnecio 99 y densitometría ósea, al igual que tratamiento farmacológico, rehabilitación y evolución. Resultados. Se incluyó a 108 pacientes, el 89% de sexo femenino, con una edad promedio de 54,8±12,4 años. El tiempo de evolución desde el comienzo de los síntomas en el momento de la consulta fue de 3,1 meses. Dentro de los factores desencadenantes, prevaleció el traumatismo con el 91,7%. La ansiedad se asoció como el factor psicológico más frecuente (42,6%). El dolor estuvo presente en el 100% de los pacientes y la limitación de la movilidad en 99,07% de los mismos. La localización más frecuente fue mano en el 75% (81/108 pacientes), seguido de síndrome hombro mano (10,9%). Se realizó radiografía comparativa en todos los casos, observando alteraciones en el 93,5%. A 32 pacientes se les realizó gammagrafía ósea en 3 fases que fueron patológicos en el 100% de los casos. Se solicitó densitometría ósea en 54 pacientes (50%). De los tratamientos indicados, todos los pacientes recibieron antiinflamatorios no esteroideos y el más frecuente fue el diclofenaco (60%). Ciento seis pacientes (98,2%) utilizaron terapia con calcio, el 97,2% vitamina D3. El 100% recibió bifosfonatos y los más utilizados fueron el alendronato y el ibandronato (el 67,6 y el 27,8%, respectivamente). Treinta y seis pacientes (33,3%) utilizaron glucocorticoides. Todos los pacientes evaluados recibieron terapia ocupacional como tratamiento rehabilitador. El tiempo de curación presentó una media de 6,31 meses (4-24). La evolución fue favorable en el 88,9% de la presente serie. Conclusión. El trabajo muestra las características clínicas, terapéuticas y evolutivas de SDRC tipo 1 observadas en 108 pacientes. Se reconoce como un síndrome heterogéneo, que no siempre presenta la sintomatología conocida y se recomienda plantear diagnóstico diferencial con otras patologías infecciosas e inflamatorias. Es importante destacar que la derivación precoz, permite un tratamiento oportuno (AU)

Introduction. Complex regional pain syndrome (CRPS) type 1 is characterized by the presence of pain, edema, functional impotence, impaired mobility, trophic changes, vasomotor instability and bone demineralization. Material and methods. We carried out a retrospective and prospective, descriptive, observational study of 108 patients over 18 years of age with suspected CRPS who met Doury's criteria. We recorded demographic data, clinical characteristics, comorbidities, previous predisposing conditions and triggering factors, such as injury or fracture. We evaluated laboratory data, serial plain X-rays, 3-phase bone scintigraphy with technetium 99 and bone density scan, as well as drug treatment, rehabilitation and disease course. Results. In all, 89% of the 108 patients were women with an average age of 54.8±12.4 years. The time between the onset of the symptoms and the first visit to a physician was 3.1 months. The most common triggering factor was injury (91.7%). The most frequent psychological factor was anxiety (42.6%). All the patients reported pain and 99.07% had impaired mobility. The most frequently affected part of the body was the hand (75%; 81/108 patients) followed by the shoulder, in the shoulder-hand syndrome. All the patients had serial X-rays and changes were observed in 93.5%. Three-phase bone scintigraphy revealed evidence of disease in all 32 of the patients who underwent this study. Bone density scanning was performed in 54 patients (50%). All the patients were treated with nonsteroidal anti-inflammatory drugs, mainly diclofenac (60%). Calcium therapy was initiated in 106 patients (98.2%) and vitamin D3 therapy in 97.2%. All the patients received bisphosphonates, primarily alendronate and ibandronate (67.6% and 27.8%, respectively). Thirty-six patients (33.3%) received corticosteroids. All of the evaluated patients underwent rehabilitation involving occupational therapy. The average time to recovery was 6.31 months (range, 4-24). The outcome was favorable in 88.9% of the patients. Conclusion. This paper describes the clinical characteristics, therapeutic features and outcome of CRPS type 1 in 108 patients. This syndrome is known to be heterogeneous, and does not always present with the well-known symptoms. We recommend establishing a differential diagnosis including other infectious and inflammatory conditions, and point out the importance of early referral, which enables early treatment (AU)

Predictors of Responsiveness to Bisphosphonate Treatment in Patients with Complex Regional Pain Syndrome Type I: A Retrospective Chart Analysis.

Objective: The aim of this study was to assess whether the effectiveness of bisphosphonate infusion in patients with complex regional pain syndrome type I (CRPS-I) is influenced by variables related to patient and/or disease characteristics. Methods: This is a retrospective analysis of patients referred in the last five years to our rheumatologic tertiary care center, all fulfilling the Budapest CRPS-I diagnostic criteria and treated with three different bisphosphonate schedules (clodronate, pamidronate, and neridronate). For every subject, demographic and clinical variables were retrieved and retrospectively analyzed. We identified variables that independently influenced the therapeutic outcome of patients by a logistic regression analysis. For exploratory purposes, the effectiveness of the different bisphosphonate treatments employed was compared. Results: Among the 194 patients included in the analysis, the overall therapeutic response rate was 71.6%. Logistic regression analysis showed that the independent predictive variables for therapeutic effectiveness were disease duration (odds ratio [OR] = 0.83, 95% confidence interval [CI] = 0.72-0.96 for a one-month increment), fracture as a predisposing event (OR = 3.23, 95% CI = 1.29-8.03), and "warm" disease subtype (OR = 4.88, 95% CI = 1.57-15.20). These variables were found to influence the odds of responsiveness when analyzed together with age at onset, gender, and disease localization. No significant difference in therapeutic effectiveness was found by comparing the three different bisphosphonate schedules employed. Conclusion: Early disease, fracture as a predisposing event, and "warm" disease subtype are predictors of responsiveness to bisphosphonate treatment in patients with CRPS-I.

Local anaesthetic sympathetic blockade for complex regional pain syndrome.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews, 2005, Issue 4 (and last updated in the Cochrane Database of Systematic Reviews, 2013 issue 8), on local anaesthetic blockade (LASB) of the sympathetic chain to treat people with complex regional pain syndrome (CRPS). OBJECTIVES: To assess the efficacy of LASB for the treatment of pain in CRPS and to evaluate the incidence of adverse effects of the procedure. SEARCH METHODS: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 9), MEDLINE (Ovid), EMBASE (Ovid), LILACS (Birme), conference abstracts of the World Congresses of the International Association for the Study of Pain, and various clinical trial registers up to September 2015. We also searched bibliographies from retrieved articles for additional studies. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that evaluated the effect of sympathetic blockade with local anaesthetics in children or adults with CRPS compared to placebo, no treatment, or alternative treatments. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The outcomes of interest were reduction in pain intensity, the proportion who achieved moderate or substantial pain relief, the duration of pain relief, and the presence of adverse effects in each treatment arm. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table. MAIN RESULTS: We included an additional four studies (N = 154) in this update. For this update, we excluded studies that did not follow up patients for more than 48 hours. As a result, we excluded four studies from the previous review in this update. Overall we included 12 studies (N = 461), all of which we judged to be at high or unclear risk of bias. Overall, the quality of evidence was low to very low, downgraded due to limitations, inconsistency, imprecision, indirectness, or a combination of these.Two small studies compared LASB to placebo/sham (N = 32). They did not demonstrate significant short-term benefit for LASB for pain intensity (moderate quality evidence).One small study (N = 36) at high risk of bias compared thoracic sympathetic block with corticosteroid and local anaesthetic versus injection of the same agents into the subcutaneous space, reporting statistically significant and clinically important differences in pain intensity at one-year follow-up but not at short term follow-up (very low quality evidence).Of two studies that investigated LASB as an addition to rehabilitation treatment, the only study that reported pain outcomes demonstrated no additional benefit from LASB (very low quality evidence).Eight small randomised studies compared sympathetic blockade to various other active interventions. Most studies found no difference in pain outcomes between sympathetic block versus other active treatments (low to very low quality evidence).One small study compared ultrasound-guided LASB with non-guided LASB and found no clinically important difference in pain outcomes (very low quality evidence).Six studies reported adverse events, all with minor effects reported. AUTHORS' CONCLUSIONS: This update's results are similar to the previous versions of this systematic review, and the main conclusions are unchanged. There remains a scarcity of published evidence and a lack of high quality evidence to support or refute the use of local anaesthetic sympathetic blockade for CRPS. From the existing evidence, it is not possible to draw firm conclusions regarding the efficacy or safety of this intervention, but the limited data available do not suggest that LASB is effective for reducing pain in CRPS.

Management of patients with complex regional pain syndrome type I.

Complex regional pain syndrome type I (CRPS-I) includes different conditions characterized by regional pain and sensory, motor, sudomotor, vasomotor, and/or trophic findings, affecting a peripheral limb usually after a noxious event, such as a trauma or surgery. The pathophysiology is still poorly understood. Limited data are available on the incidence of CRPS-I, and the disease is underestimated and under-diagnosed. The disease shows a female preponderance approximately 3:1 with a peak age of incidence around the 5th and 6th decade. The available diagnostic criteria for CRPS-I rely on clinical criteria that are unfortunately focused on the signs and symptoms of the chronic and late disease, while little emphasis is given to the typical imaging (X-rays, bone scintigraphy, MRI) findings of the early phase. Over the last decades, several therapies have been proposed but the few studies available are often too small to be conclusive and rarely evolved to randomized controlled trials (RCTs). On the basis of the results of a few RCTs, only short courses of high bisphosphonate doses appear to provide substantial benefits. The best results are seen in patients in the early phase of the disease, often with the persistent remission or complete healing of the conditions. Since the only accredited mechanism of action of bisphosphonates is the suppression of osteoclastic bone resorption, it is likely the initial dramatic bone loss plays a role in the maintenance and evolution of CRPS-I. Short courses of high doses of bisphosphonates should be considered the treatment of choice for patients with CRPS-I.

Pamidronate effect compared with a steroid on complex regional pain syndrome type I: Pilot randomised trial.

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.

A randomized controlled trial of amitriptyline versus gabapentin for complex regional pain syndrome type I and neuropathic pain in children.

BACKGROUND: Treatment of neuropathic pain in children is challenging, and requires a multimodal approach of pharmacologic, physical, and psychological therapies; however there is little evidence to guide practice. Amitriptyline and gabapentin are first-line drugs for treating neuropathic pain in adults, yet no studies have examined their efficacy, or compared them directly, to determine which might be better for pain relief and sleep disturbance in children. METHODS: After informed consent was obtained, 34 patients aged 7-18 years diagnosed with complex regional pain syndrome type I (CRPS I) or a neuropathic pain condition were randomly allocated to receive either amitriptyline or gabapentin. Patients were followed for 6 weeks and assessed for pain intensity, sleep quality and adverse events. We blinded study personnel, including health-care providers, participants, parents, the research coordinator and the data analyst. Patients then completed quantitative sensory testing (QST) and a psychosocial pain assessment with the team psychologist, within 1-3 days of the start of the trial. RESULTS: At the end of the 6-week trial, patients on both drugs had important reductions in pain, having surpassed the minimally important difference (MID) of 1. The difference between the groups however was not statistically significant. For the secondary outcomes, we found no statistically significant difference between the two drugs in sleep score or adverse events suggesting that both drugs improve sleep score to a similar degree and are equally safe. CONCLUSIONS: Amitriptyline and gabapentin significantly decreased pain intensity scores and improved sleep. There were no significant differences between the two drugs in their effects on pain reduction or sleep disability. IMPLICATIONS: Although larger, multi-centred trials are needed to confirm our findings, including long-term follow-up, both drugs appear to be safe and effective in treating paediatric patients in the first-line treatment of CRPS I and neuropathic pain over 6-weeks.