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BACKGROUND: A Mass Casualty Incident response (MCI) full scale exercise (FSEx) assures MCI first responder (FR) competencies. Simulation and serious gaming platforms (Simulation) have been considered to achieve and maintain FR competencies. The translational science (TS) T0 question was asked: how can FRs achieve similar MCI competencies as a FSEx through the use of MCI simulation exercises? METHODS: T1 stage (Scoping Review): PRISMA-ScR was conducted to develop statements for the T2 stage modified Delphi (mD) study. 1320 reference titles and abstracts were reviewed with 215 full articles progressing for full review leading to 97 undergoing data extraction.T2 stage (mD study): Selected experts were presented with 27 statements derived from T1 data with instruction to rank each statement on a 7-point linear numeric scale, where 1 = disagree and 7 = agree. Consensus amongst experts was defined as a standard deviation ≤ 1.0. RESULTS: After 3 mD rounds, 19 statements attained consensus and 8 did not attain consensus. CONCLUSIONS: MCI simulation exercises can be developed to achieve similar competencies as FSEx by incorporating the 19 statements that attained consensus through the TS stages of a scoping review (T1) and mD study (T2), and continuing to T3 implementation, and then T4 evaluation stages.
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Socorristas , Incidentes con Víctimas en Masa , Humanos , Consenso , Técnica Delphi , Ejercicio FísicoRESUMEN
PURPOSE: Infants hospitalized in the neonatal intensive care unit (NICU) may be orally fed while receiving noninvasive ventilation (NIV), but the practice is variable and decision criteria are not well understood. This systematic review examines the evidence regarding this practice, including type and level of NIV used during NICU oral feeding, protocols, and safety of this practice. METHOD: The PubMed, Scopus, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched to identify publications relevant to this review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to ensure the appropriate inclusion of articles. RESULTS: Fourteen articles were included. Seven studies (50%) were retrospective. Two were quality improvement projects, and the remaining five (35.7%) were prospective. Continuous positive airway pressure and high-flow nasal cannula were commonly used. Levels of respiratory support were variable between studies, if reported at all. Three studies (21.4%) included feeding protocols. Six studies (42.9%) identified use of feeding experts. While many studies commented that orally feeding neonates on NIV is safe, the only study to instrumentally assess swallow safety found that a significant number of neonates silently aspirated during feeding on continuous positive airway pressure. CONCLUSIONS: Strong data supporting practices related to orally feeding infants in the NICU who require NIV are scarce. The types and levels of NIV, and decision-making criteria, are variable across studies and preclude clinically useful conclusions. There is a pressing need for additional research pertaining to orally feeding this population so that an evidence-based standard of care can be established. Specifically, this research should elucidate the impact of different types and levels of NIV on the mechanistic properties of swallowing as defined via instrumental assessment.
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Ventilación no Invasiva , Recién Nacido , Lactante , Humanos , Ventilación no Invasiva/efectos adversos , Ventilación no Invasiva/métodos , Estudios Prospectivos , Estudios Retrospectivos , Respiración Artificial , Presión de las Vías Aéreas Positiva Contínua/efectos adversosRESUMEN
PURPOSE: The European Union Horizon 2020 research and innovation funding program awarded the NIGHTINGALE grant to develop a toolkit to support first responders engaged in prehospital (PH) mass casualty incident (MCI) response. To reach the projects' objectives, the NIGHTINGALE consortium used a Translational Science (TS) process. The present work is the first TS stage (T1) aimed to extract data relevant for the subsequent modified Delphi study (T2) statements. METHODS: The authors were divided into three work groups (WGs) MCI Triage, PH Life Support and Damage Control (PHLSDC), and PH Processes (PHP). Each WG conducted simultaneous literature searches following the PRISMA extension for scoping reviews. Relevant data were extracted from the included articles and indexed using pre-identified PH MCI response themes and subthemes. RESULTS: The initial search yielded 925 total references to be considered for title and abstract review (MCI Triage 311, PHLSDC 329, PHP 285), then 483 articles for full reference review (MCI Triage 111, PHLSDC 216, PHP 156), and finally 152 articles for the database extraction process (MCI Triage 27, PHLSDC 37, PHP 88). Most frequent subthemes and novel concepts have been identified as a basis for the elaboration of draft statements for the T2 modified Delphi study. CONCLUSION: The three simultaneous scoping reviews allowed the extraction of relevant PH MCI subthemes and novel concepts that will enable the NIGHTINGALE consortium to create scientifically anchored statements in the T2 modified Delphi study.
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Socorristas , Incidentes con Víctimas en Masa , Humanos , Ciencia Traslacional Biomédica , Triaje , Bases de Datos FactualesRESUMEN
PURPOSE: Unilateral spatial neglect (USN), an inability to attend to one side of space or one's body, is commonly reported in adult stroke survivors and is associated with poor outcomes. USN has been reported in pediatric survivors of stroke, but its impact is unclear. The purpose of this systematic review was to summarize and evaluate the literature regarding USN in pediatric stroke survivors. METHODS: PRISMA guidelines, Scopus, CINAHL, PubMed, and other relevant databases were searched with terms including "children", "stroke", and "unilateral neglect", with the ages of participants limited from to birth to 18 years. Data were extracted from studies on the clinical presentation of pediatric USN, the assessment of this condition, treatment options, or USN recovery. RESULTS: A total of 18 articles met inclusion criteria. There were no current prevalence data available. USN presents similarly in children compared to adults. Several different USN assessments were used, however, there were little data regarding treatment options. Furthermore, the data suggest that not all children fully recover. CONCLUSION: This systematic review reveals a lack of quality research to inform the assessment and treatment of children with USN. Although the literature spans decades, there remain no guidelines for standardized assessment or treatment. Similar to adults, paper-and-pencil testing may be less able to identify USN than functional assessments. It is likely that there are children who struggle with undetected USN-related deficits years after their injuries. With a rise of pediatric stroke survivors, there is a pressing need for clinicians to be educated about USN in children, clinical presentations, assessments, and treatments.
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Trastornos de la Percepción , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Adulto , Niño , Humanos , Trastornos de la Percepción/diagnóstico , Trastornos de la Percepción/etiología , Accidente Cerebrovascular/complicacionesRESUMEN
Purpose Despite the emphasis on using evidence-based practice for patient care, as clinicians, we sometimes find that there is insufficient evidence to support our clinical practices. One example of this is the "contentious" inclusion of routine, standardized visualization of the esophagus during modified barium swallow studies (MBSSs). This review sought to investigate the evidence for inclusion of routine esophageal visualization during the MBSS, a practice that is supported by the long-established interrelationship between all aspects of the oral, pharyngeal, and esophageal swallowing continuum. Method Searches were conducted in PubMed, Scopus, and CINAHL databases. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed to identify articles that met prespecified inclusion and exclusion terms. Results Five articles were included in this review, which identified that esophageal findings were present in 48.67% of those participants whose MBSS included esophageal visualization. Conclusion This review supports a standardized, validated, reliable visualization protocol of the esophagus during the MBSS as a critical component to the accurate diagnosis and formulation of treatment recommendations for patients with swallowing disorders.
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Trastornos de Deglución , Deglución , Bario , Trastornos de Deglución/diagnóstico , Fluoroscopía , HumanosRESUMEN
BACKGROUND: As statisticians develop new methodological approaches, there are many factors that influence whether others will utilize their work. This paper is a bibliometric study that identifies and quantifies associations between characteristics of new biostatistics methods and their citation counts. Of primary interest was the association between numbers of citations and whether software code was available to the reader. METHODS: Statistics journal articles published in 2010 from 35 statistical journals were reviewed by two biostatisticians. Generalized linear mixed models were used to determine which characteristics (author, article, and journal) were independently associated with citation counts (as of April 1, 2017) in other peer-reviewed articles. RESULTS: Of 722 articles reviewed, 428 were classified as new biostatistics methods. In a multivariable model, for articles that were not freely accessible on the journal's website, having code available appeared to offer no boost to the number of citations (adjusted rate ratio = 0.96, 95% CI = 0.74 to 1.24, p = 0.74); however, for articles that were freely accessible on the journal's website, having code available was associated with a 2-fold increase in the number of citations (adjusted rate ratio = 2.01, 95% CI = 1.30 to 3.10, p = 0.002). Higher citation rates were also associated with higher numbers of references, longer articles, SCImago Journal Rank indicator (SJR), and total numbers of publications among authors, with the strongest impact on citation rates coming from SJR (rate ratio = 1.21 for a 1-unit increase in SJR; 95% CI = 1.11 to 1.32). CONCLUSION: These analyses shed new insight into factors associated with citation rates of articles on new biostatistical methods. Making computer code available to readers is a goal worth striving for that may enhance biostatistics knowledge translation.
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Bibliometría , Publicaciones/clasificación , Bioestadística , Modelos LinealesRESUMEN
Gastrostomy feeding tubes are commonly placed in patients with dysphagia after stroke. The subsequent removal of the tube is a primary goal during rehabilitation. The purpose of our review was to identify predictors and factors associated with gastrostomy tube removal in patients with dysphagia after stroke. We conducted a literature review following the PRISMA statement and included the search databases PubMed, Scopus, Web of Science, and CINAHL. Articles were included in the final analysis per predefined inclusion and exclusion criteria. Our search retrieved a total of 853 results consisting of 416 articles (after eliminating duplicates). Six articles met our final eligibility criteria. The following factors were identified in at least 1 article as being significantly associated with gastrostomy tube removal: reduced age, decreased number of comorbidities, prolonged inpatient rehabilitation stay, absence of bilateral stroke, nonhemorrhagic stroke, reduced dysphagia severity, absence of aspiration, absence of premature bolus loss, and timely initiation of pharyngeal swallow. Aspiration was the only factor that was investigated by 2 studies-both using multiple regression and both showing stable results, with absence of aspiration increasing the chances for tube removal. In conclusion, little is known about factors associated with gastrostomy tube removal in patients with dysphagia after stroke. Most of the identified factors are associated with stroke or disease severity; however, the role of the individual factors remains unclear. The strongest predictor appears to be absence of aspiration on modified barium swallow studies emphasizing the importance of instrumental swallow studies in this patient population.
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Trastornos de Deglución/terapia , Remoción de Dispositivos , Nutrición Enteral , Gastrostomía , Accidente Cerebrovascular/terapia , Trastornos de Deglución/etiología , Humanos , Accidente Cerebrovascular/complicacionesRESUMEN
Gastrostomy feeding tubes are commonly placed in patients with dysphagia after stroke. The subsequent removal of the tube is a primary goal during rehabilitation. The purpose of our review was to identify predictors and factors associated with gastrostomy tube removal in patients with dysphagia after stroke. We conducted a literature review following the PRISMA statement and included the search databases PubMed, Scopus, Web of Science, and CINAHL. Articles were included in the final analysis per predefined inclusion and exclusion criteria. Our search retrieved a total of 853 results consisting of 416 articles (after eliminating duplicates). Six articles met our final eligibility criteria. The following factors were identified in at least 1 article as being significantly associated with gastrostomy tube removal: reduced age, decreased number of comorbidities, prolonged inpatient rehabilitation stay, absence of bilateral stroke, nonhemorrhagic stroke, reduced dysphagia severity, absence of aspiration, absence of premature bolus loss, and timely initiation of pharyngeal swallow. Aspiration was the only factor that was investigated by 2 studies-both using multiple regression and both showing stable results, with absence of aspiration increasing the chances for tube removal. In conclusion, little is known about factors associated with gastrostomy tube removal in patients with dysphagia after stroke. Most of the identified factors are associated with stroke or disease severity; however, the role of the individual factors remains unclear. The strongest predictor appears to be absence of aspiration on modified barium swallow studies emphasizing the importance of instrumental swallow studies in this patient population.
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Trastornos de Deglución/terapia , Remoción de Dispositivos , Gastrostomía , Accidente Cerebrovascular/complicaciones , Comorbilidad , Trastornos de Deglución/etiología , Práctica Clínica Basada en la Evidencia , Humanos , Pacientes InternosRESUMEN
OBJECTIVE: Maternal stress in humans influences behavior of children and can be assessed using biological markers. Mothers and their one-month-old infants were recruited from an existing study to examine baseline maternal serum oxytocin and hypothalamic-pituitary-adrenal axis response to infant blood heel stick stress as measured by salivary cortisol in the dyads. Objectives were to explore (1) relationships between mother and infant cortisol levels, (2) gender differences in infant biologic cortisol response, and (3) the association of cortisol levels in the dyads and maternal oxytocin levels METHODS: Forty-two mother-infant dyads provided biologic samples and self-report data. Maternal oxytocin samples were obtained. Initial salivary cortisol was assessed in both the mother and infant, followed by a heel stick blood draw. Twenty minutes later, salivary cortisol was collected again from dyads. RESULTS: Self-report measures were negative for depression and risk for childhood neglect. Although oxytocin and baseline cortisol in the infants was higher in mothers that did some breast-feeding, there was no statistically significant difference (p = 0.2 and p = 0.1, respectively). Analyses showed (a) higher baseline cortisol in mothers was related to higher baseline cortisol in infants (p ≤ 0.0001), (b) following the stressor, female infants had a larger positive change in cortisol, after adjusting for baseline cortisol (p = 0.045), and (c) there was no relationship between dyad cortisol levels and maternal oxytocin. CONCLUSIONS: Maternal and infant biologic stress measures are related. Female infants have a larger hypothalamic-pituitary-adrenal response to a blood draw stressor as measured by salivary cortisol than male infants.
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Hidrocortisona/análisis , Sistema Hipotálamo-Hipofisario/fisiopatología , Relaciones Madre-Hijo , Madres/psicología , Apego a Objetos , Sistema Hipófiso-Suprarrenal/fisiopatología , Estrés Psicológico/fisiopatología , Biomarcadores , Depresión , Femenino , Humanos , Lactante , Masculino , Oxitocina/sangre , Saliva/química , Estrés Psicológico/sangre , Estrés Psicológico/psicologíaRESUMEN
OBJECTIVES: To perform a systematic review of the growing body of literature evaluating the prognostic value of epicardial fat volume (EFV) quantified by cross-sectional imaging. METHODS: Two independent reviewers performed systematic searches on both PubMed and Scopus using search terms developed with a medical librarian. Peer-reviewed articles were selected based on the inclusion of outcome data, utilization of epicardial fat volume and sufficient reporting for analysis. RESULTS: A total of 411 studies were evaluated with nine studies meeting the inclusion criteria. In all, the studies evaluated 10,252 patients. All nine studies were based on CT measurements. Seven studies evaluated the prognostic value of EFV unadjusted for calcium score, and six of these studies found a significant association between EFV and clinical outcomes. Seven studies evaluated the incremental value of EFV beyond calcium scoring, and six of these studies found a significant association. CONCLUSIONS: The majority of studies suggest that EFV quantification is significantly associated with clinical outcomes and provides incremental prognostic value over coronary artery calcium scoring. Future research should use a binary cutoff of 125 mL for evaluation of EFV to provide consistency with other research. KEY POINTS: ⢠Epicardial fat volume (EFV) has prognostic value for adverse cardiac events ⢠Establishment of standardized quantitative categories for EFV is needed ⢠Quantification of EFV could improve risk assessment with calcium scoring.
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Tejido Adiposo/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Pericardio/diagnóstico por imagen , Calcificación Vascular/diagnóstico por imagen , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Prior genetic correlation analysis of 22 heritable behavioral measures of nociception and hypersensitivity in the mouse identified 5 genetically distinct pain types. In the present study, we reanalyzed that dataset and included the results of an additional 9 assays of nociception and hypersensitivity, with the following goals: to replicate the previously identified 5 pain types; to test whether any of the newly added pain assays represent novel genetically distinct pain types; and to test the level of genetic relatedness among 9 commonly used neuropathic pain assays. Multivariate analysis of pairwise correlations between assays shows that the newly added zymosan-induced heat hypersensitivity assay does not conform to the 2 previously identified groups of heat hypersensitivity assays and cyclophosphamide-induced cystitis, the first organ-specific visceral pain model examined, is genetically distinct from other inflammatory assays. The 4 included mechanical hypersensitivity assays are genetically distinct and do not comprise a single pain type as previously reported. Among the 9 neuropathic pain assays including autotomy, chemotherapy, nerve ligation and spared nerve injury assays, at least 4 genetically distinct types of neuropathic sensory abnormalities were identified, corresponding to differences in nerve injury method. In addition, 2 itch assays and Comt genotype were compared to the expanded set of nociception and hypersensitivity assays. Comt genotype was strongly related only to spontaneous inflammatory nociception assays. These results indicate the priority for continued investigation of genetic mechanisms in several assays newly identified to represent genetically distinct pain types.
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Hiperalgesia/genética , Neuralgia/genética , Nocicepción/fisiología , Dimensión del Dolor , Traumatismos de los Nervios Periféricos/genética , Animales , Conducta Animal , Modelos Animales de Enfermedad , Masculino , Ratones , Traumatismos de los Nervios Periféricos/etiologíaRESUMEN
BACKGROUND: Novel statistical methods are constantly being developed within the context of biomedical research; however, the characteristics of biostatistics methods that have been adopted into the field of general/internal medicine (GIM) is unclear. This study highlights the statistical journal articles, the statistical journals, and the types of statistical methods that appear to be having the most direct impact on GIM research. METHODS: Descriptive techniques, including analyses of articles' keywords and controlled vocabulary terms, were used to characterize the articles published in statistics and probability journals that were subsequently referenced within GIM journal articles during a recent 10-year period (2000-2009). RESULTS: From the 45 statistics and probability journals of interest, a total of 989 unique articles were identified as being cited by 2183 (out of a total of about 127 469) unique GIM journal articles. The most frequently cited statistical topics included general/other statistical methods, followed by randomized trials, epidemiologic methods, meta-analysis, generalized linear models, and computer simulation. CONCLUSION: As statisticians continue to develop and refine techniques, the promotion and adoption of these methods should also be addressed so that their efforts spent in developing the methods are not done in vain.
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Bioestadística/métodos , Medicina Interna/métodos , Edición , Humanos , Medicina Interna/normasRESUMEN
Chronic pain is highly variable between individuals, as is the response to analgesics. Although much of the variability in chronic pain and analgesic response is heritable, an understanding of the genetic determinants underlying this variability is rudimentary. Here we show that variation within the coding sequence of the gene encoding the P2X7 receptor (P2X7R) affects chronic pain sensitivity in both mice and humans. P2X7Rs, which are members of the family of ionotropic ATP-gated receptors, have two distinct modes of function: they can function through their intrinsic cationic channel or by forming nonselective pores that are permeable to molecules with a mass of up to 900 Da. Using genome-wide linkage analyses, we discovered an association between nerve-injury-induced pain behavior (mechanical allodynia) and the P451L mutation of the mouse P2rx7 gene, such that mice in which P2X7Rs have impaired pore formation as a result of this mutation showed less allodynia than mice with the pore-forming P2rx7 allele. Administration of a peptide corresponding to the P2X7R C-terminal domain, which blocked pore formation but not cation channel activity, selectively reduced nerve injury and inflammatory allodynia only in mice with the pore-forming P2rx7 allele. Moreover, in two independent human chronic pain cohorts, a cohort with pain after mastectomy and a cohort with osteoarthritis, we observed a genetic association between lower pain intensity and the hypofunctional His270 (rs7958311) allele of P2RX7. Our findings suggest that selectively targeting P2X7R pore formation may be a new strategy for individualizing the treatment of chronic pain.
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Dolor Crónico/genética , Mutación/genética , Umbral del Dolor/fisiología , Receptores Purinérgicos P2X7/genética , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Animales , Benzoxazoles/metabolismo , Calcio/metabolismo , Carbenoxolona/farmacología , Células Cultivadas , Dolor Crónico/etiología , Dolor Crónico/patología , Estudios de Cohortes , Conexinas/metabolismo , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Femenino , Ligamiento Genético , Estudio de Asociación del Genoma Completo , Genotipo , Histidina/genética , Humanos , Hiperalgesia/genética , Hiperalgesia/fisiopatología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Mastectomía/efectos adversos , Ratones , Ratones Endogámicos , Proteínas del Tejido Nervioso/metabolismo , Osteoartritis/complicaciones , Dimensión del Dolor , Péptidos/farmacología , Polimorfismo de Nucleótido Simple/genética , Compuestos de Quinolinio/metabolismo , Estudios Retrospectivos , Especificidad de la Especie , Factores de Tiempo , TransfecciónRESUMEN
Partial peripheral nerve injury in adult rats results in neuropathic pain-like hypersensitivity, while that in neonatal rats does not, a phenomenon also observed in humans. We therefore compared gene expression profiles in the dorsal horn of adult and neonatal rats in response to the spared nerve injury (SNI) model of peripheral neuropathic pain. The 148 differentially regulated genes in adult, but not young, rat spinal cords indicate a greater microglial and T-cell response in adult than in young animals. T-cells show a large infiltration in the adult dorsal horn but not in the neonate after SNI. T-cell-deficient Rag1-null adult mice develop less neuropathic mechanical allodynia than controls, and central expression of cytokines involved in T-cell signaling exhibits large relative differences between young and adult animals after SNI. One such cytokine, interferon-gamma (IFNgamma), is upregulated in the dorsal horn after nerve injury in the adult but not neonate, and we show that IFNgamma signaling is required for full expression of adult neuropathic hypersensitivity. These data reveal that T-cell infiltration and activation in the dorsal horn of the spinal cord following peripheral nerve injury contribute to the evolution of neuropathic pain-like hypersensitivity. The neuroimmune interaction following peripheral nerve injury has therefore a substantial adaptive immune component, which is absent or suppressed in the young CNS.
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Movimiento Celular/inmunología , Hipersensibilidad/patología , Neuralgia/inmunología , Dolor/inmunología , Células del Asta Posterior/inmunología , Transducción de Señal , Médula Espinal/inmunología , Linfocitos T/patología , Factores de Edad , Animales , Hipersensibilidad/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Desnudos , Neuralgia/patología , Dolor/patología , Dimensión del Dolor/métodos , Células del Asta Posterior/crecimiento & desarrollo , Células del Asta Posterior/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/inmunología , Médula Espinal/crecimiento & desarrollo , Médula Espinal/patología , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Nociceptive-selective local anesthesia is produced by entry of the permanently charged lidocaine-derivative QX-314 into nociceptors when coadministered with capsaicin, a transient receptor potential vanilloid 1 (TRPV1) channel agonist. However, the pain evoked by capsaicin before establishment of the QX-314-mediated block would limit clinical utility. Because TRPV1 channels are also activated by lidocaine, the authors tested whether lidocaine can substitute for capsaicin to introduce QX-314 into nociceptors through TRPV1 channels and produce selective analgesia. METHODS: Lidocaine (0.5% [17.5 mM], 1% [35 mM], and 2% [70 mM]) alone, QX-314 (0.2% [5.8 mM]) alone, and a combination of the two were injected subcutaneously and adjacent to the sciatic nerve in rats and mice. Mechanical and thermal responsiveness were measured, as was motor block. RESULTS: Coapplication of 0.2% QX-314 with lidocaine prolonged the nociceptive block relative to lidocaine alone, an effect attenuated in TRPV1 knockout mice. The 0.2% QX-314 alone had no effect when injected intraplantary or perineurally, and it produced only weak short-lasting inhibition of the cutaneous trunci muscle reflex. Perisciatic nerve injection of lidocaine with QX-314 produced a differential nociceptive block much longer than the transient motor block, lasting 2 h (for 1% lidocaine) to 9 h (2% lidocaine). Triple application of lidocaine, QX-314, and capsaicin further increased the duration of the differential block. CONCLUSIONS: Coapplication of lidocaine and its quaternary derivative QX-314 produces a long-lasting, predominantly nociceptor-selective block, likely by facilitating QX-314 entry through TRPV1 channels. Delivery of QX-314 into nociceptors by using lidocaine instead of capsaicin produces sustained regional analgesia without nocifensive behavior.
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Lidocaína/análogos & derivados , Lidocaína/administración & dosificación , Dimensión del Dolor/efectos de los fármacos , Bloqueadores de los Canales de Sodio/administración & dosificación , Animales , Células Cultivadas , Quimioterapia Combinada , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Dimensión del Dolor/métodos , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Peripheral nerve injuries that provoke neuropathic pain are associated with microglial activation in the spinal cord. We have investigated the characteristics of spinal microglial activation in three distinct models of peripheral neuropathic pain in the rat: spared nerve injury (SNI), chronic constriction injury, and spinal nerve ligation. In all models, dense clusters of cells immunoreactive for the microglial marker CD11b formed in the ipsilateral dorsal horn 7 days after injury. Microglial expression of ionised calcium binding adapter molecule 1 (Iba1) increased by up to 40% and phosphorylation of p38 mitogen-activated protein kinase, a marker of microglial activity, by 45%. Expression of the lysosomal ED1-antigen indicated phagocytic activity of the cells. Unlike the peripheral nerve lesions, rhizotomy produced only a weak microglial reaction within the spinal gray matter but a strong activation of microglia and phagocytes in the dorsal funiculus at lumbar and thoracic spinal cord levels. This suggests that although degeneration of central terminals is sufficient to elicit microglial activation, it does not account for the inflammatory response in the dorsal horn after peripheral nerve injury. Early intrathecal treatment with low-dose methotrexate, beginning at the time of injury, decreased microglial activation, reduced p38 phosphorylation, and attenuated pain-like behavior after SNI. In contrast, systemic or intrathecal delivery of the glucocorticoid dexamethasone did not inhibit the activation of microglia or reduce pain-like behavior. We confirm that microglial activation is crucial for the development of pain after nerve injury, and demonstrates that suppression of this cellular immune response is a promising approach for preventing neuropathic pain.