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To explore serum levels of some bone turnover markers and the involvement of the Wnt signaling in CRPS-1. Query ID="Q1" Text="Please check and confirm whether the edit made to the article title is in order." We conducted an observational study on patients with early CRPS-1 recruited before any treatment. Clinical measures were assessed together with biochemical evaluation. Values of sclerostin, DKK1, CTX-I, and P1NP were compared with sex-age-matched healthy controls (HCs). We enrolled 34 patients diagnosed with CRPS-1 (mean age 59.3 ± 10.6 years, Male/Female 10/24), median disease duration = 2 weeks (IQR 1-5); median VAS score = 76 (IQR 68-80). Foot localization was slightly more frequent than hand localization (18/16). No statistically significant difference was found between CRPS-1 patients and HCs for CTX-I (0.3 ± 0.1 ng/ml vs 0.3 ± 0.1, p = 0.140), while mean serum values of P1NP were significantly higher in CRPS-1 patients compared to HCs (70.0 ± 38.8 ng/ml vs 50.1 ± 13.6, p = 0.005). Mean levels of sclerostin and DKK1 were lower in CRPS-1 patients vs HCs (sclerostin 28.4 ± 10.8 pmol/l vs 34.1 ± 11.6, p = 0.004; DKK1 12.9 ± 10.8 pmol/l vs 24.1 ± 11.9, p = 0.001). No statistically significant difference was found for all biochemical assessments in a subgroup of fracture-induced CRPS-1. No statistically significant differences were observed according to disease localization, disease duration, presence of hyperalgesia, allodynia, sudomotor alterations, and mild or moderate/severe swelling. No significant correlation emerged between sclerostin, DKK1 levels, baseline VAS score, or McGill Pain Questionnaire score. Bone involvement in early CRPS-1 does not seem to rely on increased osteoclast activity. Conversely, a serum marker of bone formation resulted increased. Both Sclerostin and DKK1 showed decreased values, probably suggesting a widespread osteocyte loss of function.Trial registration number: Eudract Number: 2014-001156-28.
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Biomarcadores , Remodelación Ósea , Vía de Señalización Wnt , Humanos , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Anciano , Remodelación Ósea/fisiología , Vía de Señalización Wnt/fisiología , Síndromes de Dolor Regional Complejo/sangre , Síndromes de Dolor Regional Complejo/metabolismo , Péptidos y Proteínas de Señalización Intercelular/sangre , Proteínas Adaptadoras Transductoras de Señales/sangreRESUMEN
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.
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Conservadores de la Densidad Ósea/uso terapéutico , Huesos/efectos de los fármacos , Difosfonatos/uso terapéutico , Distrofia Simpática Refleja/tratamiento farmacológico , Conservadores de la Densidad Ósea/efectos adversos , Huesos/metabolismo , Huesos/fisiopatología , Citocinas/metabolismo , Difosfonatos/efectos adversos , Humanos , Mediadores de Inflamación/metabolismo , Dimensión del Dolor , Distrofia Simpática Refleja/diagnóstico , Distrofia Simpática Refleja/metabolismo , Distrofia Simpática Refleja/fisiopatología , Transducción de Señal/efectos de los fármacos , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: Complex regional pain syndrome (CRPS) refers to a chronic pain condition that is characterized by progressively worsening spontaneous regional pain without dermatomal distribution. The symptomatology includes pain out of proportion in time and severity to the inciting event. The purpose of this review is to present the most current information concerning epidemiology, diagnosis, pathophysiology, and therapy for CRPS. RECENT FINDINGS: In recent years, discovery of pathophysiologic mechanisms of CRPS has led to significant strides in the understanding of the disease process. Continued elucidation of the underlying pathophysiological mechanisms will allow for the development of more targeted and effective evidence-based therapy protocols. Further large clinical trials are needed to investigate mechanisms and treatment of the disorder.
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Síndromes de Dolor Regional Complejo/terapia , Manejo del Dolor/métodos , Dimensión del Dolor/métodos , Síndromes de Dolor Regional Complejo/diagnóstico , Síndromes de Dolor Regional Complejo/epidemiología , Medicina Basada en la Evidencia , Humanos , Incidencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Complex regional pain syndrome (CRPS) occurs due to different pathophysiological mechanisms. Presently there is no description of definitive treatment that can resolve the especially recalcitrant motor issues of disability in CRPS type 1 (CRPS-1). CASE REPORT: We have herein described the successful management of motor disability with a multimodal approach in a patient with CRPS-1 that occurred as a result of a fracture sustained in the lower end of the radius. Sensory/sudomotor/vasomotor symptoms were relieved completely by medications and stellate ganglion block in 2 weeks. Ultrasound-guided dry needling secured near-complete improvement of shoulder and hand movements in 45 days. Ultrasound guided intra-articular (radio-ulnar and radio-humeral joint) injections with steroid reduced residual pain and improved forearm movements by 50% initially. The patient continued to receive regular sessions of dry needling, physiotherapy, and cognitive behavioral therapy. By the end of 1 year, the functions of the limb improved remarkably, as did the functional outcome scores. CONCLUSION: In this patient with CRPS-1, intra-articular injections with steroid reduced nociception in the affected local structures and sensitization in the nervous system; dry needling resolved the myofascial issues; sustained physiotherapy maintained the motor recovery; and behavioral therapy techniques addressed the cognitive and life stress issues. It was concluded that the presenting symptoms in this case were a consequence of interactions between humoral, nervous, and myofascial systems.
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Terapia Combinada/métodos , Síndromes de Dolor Regional Complejo/terapia , Hombro , Terapia por Acupuntura/métodos , Adulto , Femenino , Humanos , Inyecciones Intraarticulares , Síndromes del Dolor Miofascial/etiología , Síndromes del Dolor Miofascial/terapia , Bloqueo Nervioso/métodos , Modalidades de Fisioterapia , Pronación , Radio (Anatomía)/lesiones , Distrofia Simpática Refleja/etiología , Distrofia Simpática Refleja/terapia , Hombro/diagnóstico por imagen , Hombro/fisiopatología , Ultrasonografía Intervencional/métodosRESUMEN
BACKGROUND: Reflex sympathetic dystrophy (RSD) syndrome is a multifactorial disorder with clinical features of neurogenic inflammation that causes hypersensitivity to pain or severe allodynia as well as blood flow problems, swelling, skin discoloration and maladaptive neuroplasticity due to vasomotor disorders. Patients with major trauma are prone to homeostasis leading to inflammatory response syndrome and multiple organ distress syndrome. Several studies have investigated the etiology of this condition, but the cause remains unknown. The role of associated factors such as the limb immobilization technique and genetics has been reported in the development of this complication, but, so far, there is no information regarding the effect of trauma severity on the risk of RSD occurrence. OBJECTIVES: Given the importance of diagnosing and treating this condition, we aimed to study the effect of trauma severity on the prevalence of RSD. PATIENTS AND METHODS: In this cross-sectional study, we examined patients with distal tibial fracture who visited Rasht Poursina hospital from 2010 to 2013. Exclusion criteria included associated fractures, underlying musculoskeletal diseases and mental and cognitive problems. To assess the severity of the initial injury in patients, the Hannover Fracture Scale 98 (HFS98) scoring checklist was used. The diagnosis of RSD was made on the basis of the IASP criterion. Demographic data, HFS98 scores, and information regarding RSD prevalence were analyzed using SPSS version 20. The Mann Whitney U nonparametric test was used for variables that were not normally distributed; the chi-square test was used to compare the qualitative variables. RESULTS: Among the 488 patients, 292 (59.83%) were male. The mean age of the study population was 44 ± 9.82 years. During the 6-month follow-up, RSD occurred in 45 patients, of whom 28 (62.22%) were female and 17 (37.77%) were male; there was thus a significant difference in the prevalence of RSD in terms of gender (P = 0.00; chi square test). The mean HFS98 score in patients without and with RSD was 3.081 ± 4.083 and 4.080 ± 4.622, respectively, and the difference was not statistically significant (P = 0.363; Mann Whitney U test). Analyses of the eight items of HFS98 shows that local circulation in patients with RSD is significantly better than that in patients without RDS (0.683 ± 0.822 vs. 0.528 ± 0.629, respectively). Statistical analysis showed that the odds ratio for RSD for patients with HFS95 score > 0 was 1.079 (confidence interval [CI]: 0.898 - 1.333). Moreover, the odds ratio for RSD was 1.100 (CI: 795 - 1.531) in patients with an injury severity score higher than the calculated mean score in patients without RSD (> 4.083). CONCLUSIONS: The results suggest no significant relationship between the severity of injury and risk of RSD occurrence, although the mean injury severity score was higher in patients with RSD than in those without RSD in this study population. The lower score of local circulation in patients with RSD than in those without RSD is a statistically significant finding and can be attributed to changes in the antioxidant levels at the injury site, which is one of the main mechanisms for the onset of RSD. Wound contamination was also justifiably higher in patients with RSD, although the difference was not statistically significant. In summary, the severity of injury alone cannot be a determining factor for predicting the probability of RSD.
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Complex regional pain syndrome type 1 (CRPS1) may be evoked by ischemia/reperfusion, eliciting acute and chronic pain that is difficult to treat. Despite this, the underlying mechanism of CRPS1 has not been fully elucidated. Therefore, the goal of this study is to evaluate the involvement of inflammation, oxidative stress, and the transient receptor potential ankyrin 1 (TRPA1) channel, a chemosensor of inflammation and oxidative substances, in an animal model of chronic post-ischemia pain (CPIP). Male Wistar rats were subjected to 3 h hind paw ischemia/reperfusion (CPIP model). Different parameters of nociception, inflammation, ischemia, and oxidative stress were evaluated at 1 (acute) and 14 (chronic) days after CPIP. The effect of a TRPA1 antagonist and the TRPA1 immunoreactivity were also observed after CPIP. In the CPIP acute phase, we observed mechanical and cold allodynia; increased levels of tumor necrosis factor-α (hind paw), ischemia-modified albumin (IMA) (serum), protein carbonyl (hind paw and spinal cord), lactate (serum), and 4-hydroxy-2-nonenal (4-HNE, hind paw and spinal cord); and higher myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAGase) activities (hind paw). In the CPIP chronic phase, we detected mechanical and cold allodynia and increased levels of IMA (serum), protein carbonyl (hind paw and spinal cord), and 4-HNE (hind paw and spinal cord). TRPA1 antagonism reduced mechanical and cold allodynia 1 and 14 days after CPIP, but no change in TRPA1 immunoreactivity was observed. Different mechanisms underlie acute (inflammation and oxidative stress) and chronic (oxidative stress) phases of CPIP. TRPA1 activation may be relevant for CRPS1/CPIP-induced acute and chronic pain.
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Dolor Agudo/metabolismo , Dolor Crónico/metabolismo , Miembro Posterior/irrigación sanguínea , Nocicepción , Distrofia Simpática Refleja/metabolismo , Canales Catiónicos TRPC/antagonistas & inhibidores , Acetilglucosaminidasa/metabolismo , Dolor Agudo/etiología , Aldehídos/metabolismo , Animales , Dolor Crónico/etiología , Frío , Hiperalgesia/etiología , Hiperalgesia/metabolismo , Ácido Láctico/sangre , Masculino , Estrés Oxidativo , Peroxidasa/metabolismo , Carbonilación Proteica , Ratas , Ratas Wistar , Distrofia Simpática Refleja/etiología , Daño por Reperfusión/complicaciones , Albúmina Sérica/metabolismo , Canal Catiónico TRPA1 , Canales Catiónicos TRPC/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVE: To assess the effects of intravenous administration of magnesium on complex regional pain syndrome type 1 (CRPS-1), a randomized double-blind placebo-controlled trial was performed. METHODS: Fifty-six patients with CRPS-1 (International Association for the Study of Pain Orlando criteria) received MgSO(4) 70 mg/kg or placebo (NaCl 0.9%) in 4 hours over 5 consecutive days. Pain (BOX-11 and McGill), the level of impairment (Impairment level Sum Score [ISS]), functional limitations (Radboud Skills Questionnaire, Walking Skills Questionnaire/questionnaire rising and sitting down), participation (Impact on Participation and Autonomy [IPA]), and quality of life (Short Form-36, EuroQol, IPA) were evaluated at baseline and at 1, 3, 6, and 12 weeks. RESULTS: No significant differences were found between MgSO(4) and placebo on the BOX-11 and ISS at different time points during the trial on intention-to-treat and per-protocol analysis. A significant improvement on the BOX-11 was found after the first week of the trial in both groups (mean 0.7; standard deviation 1.1). For the MgSO(4) group, a clinically relevant and statistically significant improvement on the ISS at 1 week (median 5, interquartile range [IQR] -1 to 8) and a significant improvement on the McGill up to 6 weeks (median 2 words, IQR 0-4.5) were found compared with baseline, which were not found in the placebo group. Significant improvement in perceived job participation was found for the MgSO(4) group at 12 weeks (median improvement 1.44-1.17; P = 0.01). ISS improved significantly more in patients with a low Hospital Anxiety and Depression Scale (HADS) score (≤10) in the MgSO(4) group (mean 4.4 vs mean -3.1; P = 0.02). CONCLUSION: Administration of the physiological competitive N-methyl-D-aspartate receptor antagonist magnesium in chronic CRPS provides insufficient benefit over placebo. Future research should focus on patients with acute CRPS and early signs and symptoms of central sensitization.
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Analgésicos/administración & dosificación , Sulfato de Magnesio/administración & dosificación , Umbral del Dolor/efectos de los fármacos , Distrofia Simpática Refleja/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Calidad de Vida , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidoresRESUMEN
OBJECTIVES: Spinal cord stimulation (SCS) is an effective treatment for intractable complex regional pain syndrome type I pain. Long-term data are scarce on effectiveness, degree of pain relief, predictors, and complications. MATERIALS AND METHODS: From 1997 to 2008, 84 consecutive patients who received an implanted SCS system after positive test stimulation were included in the prospective study. Treatment effectiveness was assessed annually as measured by mean visual analog scale pain scores and with the Patients Global Impression of Change scale. Treatment success was defined as at least 30% mean pain relief at end point and treatment failure as explantation of the system. A Cox regression determined if baseline factors were associated with both these outcomes. RESULTS: During 11 years, 41% (95% CI: 27-55) of the patients experience at least 30% pain relief at assessment end point. During 12 years of follow-up 63% (95%CI: 41-85) of the implanted patients still use their SCS device at measured end point. Pain relief of at least 50% one week following test stimulation is associated with a higher probability of long-term treatment success. In 51 patients, 122 reinterventions were performed over 12 years; 13 were due to complications, 44 to battery changes, and 65 reinterventions were equipment related. CONCLUSION: SCS provides an effective long-term pain treatment for 63% (95%CI: 41-85) of implanted patients. Forty-one percent (95%CI: 27-55) of SCS treated patients have at least 30% pain reduction at measurement end point. The number of reinterventions after implantation due to equipment-related problems, battery changes, and complications is 122 over 12 years of follow-up. Sixty-one percent (N = 51) of the patients had at least one reintervention. Mean pain relief of at least 50% (visual analog scale) one week after the test stimulation is associated with long-term treatment success.