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OBJECTIVE: The purpose of this study was to explore brain morphological and functional connectivity alterations in adolescents with new daily persistent headache (NDPH) compared to pain-free, healthy controls. BACKGROUND: NDPH is one of the most disabling and least understood primary headache conditions. To date, no studies have considered the role of brain function and structure in pediatric patients with NDPH. METHODS: In this cross-sectional study, resting-state functional and structural images were acquired for 13 patients with NDPH (M age = 15.9, standard deviation [SD] ± 1.4) and 13 age- and sex-matched controls (M age = 16.2, SD ± 1.8) using magnetic resonance imaging. Participants were recruited from the Pediatric Headache Program at Boston Children's Hospital and from the Greater Boston area. In patients, clinical features of NDPH, including disease duration, pain intensity ratings, pain sensitivity, and functional disability were also assessed, and their associations with functional and structural brain alterations were explored. RESULTS: Compared to controls, patients with NDPH demonstrated reduced cortical thickness in the bilateral superior temporal gyrus, left superior, and middle frontal gyrus areas (p < 0.05, Monte Carlo corrected for multiple comparisons). Furthermore, reduced cortical thickness of the left superior frontal gyrus was related to elevated pain sensitivity in NDPH (r = -0.79, p = 0.006). Patients showed altered functional connectivity between regions involved in emotional and cognitive networks of pain, including the amygdala, insula, frontal regions, and cerebellar subregions. CONCLUSION: The present study provides the first preliminary evidence of functional and structural brain differences in pediatric patients with NDPH compared to controls. Identifying alterations in cortical thickness and resting-state connectivity between specific brain regions could provide characteristics of NDPH and probable mechanisms that may guide personalized therapeutic interventions.
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Trastornos de Cefalalgia , Imagen por Resonancia Magnética , Adolescente , Encéfalo/diagnóstico por imagen , Niño , Estudios Transversales , Cefalea/diagnóstico por imagen , Trastornos de Cefalalgia/terapia , HumanosRESUMEN
OBJECTIVE: To assess for differences in headache characteristics and psychosocial factors based on headache diagnosis, and to evaluate whether headache diagnosis moderates relations between psychosocial factors and school difficulties. METHODS: Retrospective chart review was conducted with 262 adolescents with chronic tension-type headache (TTH; N = 153) and migraine evaluated at a pediatric headache clinic. Adolescents completed measures of anxiety, depression, and pain coping. Parents completed a measure of parental protective behavior and school functioning. RESULTS: Adolescents with TTH reported greater depression symptoms, and their parents endorsed greater school difficulties, whereas parents of adolescents with migraine reported more protective parenting. Protective parenting was positively associated with school difficulties in both groups, but the relation was significantly stronger in adolescents with TTH. Headache duration and depression symptoms were significant predictors of school functioning in both groups. CONCLUSIONS: Headache duration and depression may impact school functioning independent of headache diagnosis. Protective parenting, in particular, seems to be linked to school-related disability in adolescents with TTH, and this link may be important to consider in assessment and treatment.
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Depresión/psicología , Trastornos Migrañosos/psicología , Responsabilidad Parental/psicología , Cefalea de Tipo Tensional/psicología , Logro , Adolescente , Adulto , Ansiedad/epidemiología , Ansiedad/fisiopatología , Ansiedad/psicología , Niño , Comorbilidad , Depresión/epidemiología , Depresión/fisiopatología , Femenino , Humanos , Masculino , Trastornos Migrañosos/epidemiología , Trastornos Migrañosos/fisiopatología , Dimensión del Dolor , Estudios Retrospectivos , Instituciones Académicas , Cefalea de Tipo Tensional/epidemiología , Cefalea de Tipo Tensional/fisiopatologíaRESUMEN
Functional imaging has revolutionized the neurosciences. In the pain field it has dramatically altered our understanding of how the brain undergoes significant functional, anatomical and chemical changes in patients with chronic pain. However, most studies have been performed in adults. Because functional imaging is non-invasive and can be performed in awake individuals, applications in children have become more prevalent, but only recently in the pain field. Measures of changes in the brains of children have important implications in understanding neural plasticity in response to acute and chronic pain in the developing brain. Such findings may have implications for treatments in children affected by chronic pain and provide novel insights into chronic pain syndromes in adults. In this review we summarize this potential and discuss specific concerns related to the imaging of pain in children.
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Imagen por Resonancia Magnética/métodos , Dolor , Espectroscopía Infrarroja Corta/métodos , Mapeo Encefálico , Niño , Humanos , Dolor/patología , Dolor/fisiopatologíaRESUMEN
Migraine is a disease that peaks in late adolescence and early adulthood. The aim of this study was to evaluate age-related brain changes in resting state functional connectivity (rs-FC) in migraineurs vs. age-sex matched healthy controls at two developmental stages: adolescence vs. young adulthood. The effect of the disease was assessed within each developmental group and age- and sex-matched healthy controls and between developmental groups (migraine-related age effects). Globally the within group comparisons indicated more widespread abnormal rs-FC in the adolescents than in the young adults and more abnormal rs-FC associated with sensory networks in the young adults. Direct comparison of the two groups showed a number of significant changes: (1) more connectivity changes in the default mode network in the adolescents than in the young adults; (2) stronger rs-FC in the cerebellum network in the adolescents in comparison to young adults; and (3) stronger rs-FC in the executive and sensorimotor network in the young adults. The duration and frequency of the disease were differently associated with baseline intrinsic connectivity in the two groups. fMRI resting state networks demonstrate significant changes in brain function at critical time point of brain development and that potentially different treatment responsivity for the disease may result.
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Fewer randomized clinical trials (RCTs) are conducted for chronic or recurrent pain in pediatric populations compared with adult populations; thus, data to support treatment efficacy in children are limited. This article evaluates the design features and reporting practices of RCTs for chronic and recurrent pain that are likely unique to, or particularly important in, a pediatric population to promote improvements in the evidence base for pediatric pain treatments. Areas covered include outcome measure selection and reporting and reporting of adverse events and challenges to recruitment and retention. A search of PubMed and EMBASE identified primary publications describing RCTs of treatments for select chronic and recurrent pain conditions in children or adolescents published between 2000 and 2017. Only 49% of articles identified a primary outcome measure. The primary outcome measure assessed pain intensity in 38% of the trials, specifically measure by verbal rating scale (13%), faces pain scale (11%), visual analogue scale (9%), or numeric rating scale (5%). All of the CONSORT harms reporting recommendations were fulfilled by <50% of the articles. Discussions of recruitment challenges occurred in 64% of articles that enrolled <90% of their target sample. However, discussions regarding retention challenges only occurred in 14% of trials in which withdrawal rates were >10%. The goal of this article is to promote comprehensive reporting of pediatric pain RCTs to improve the design of future trials, facilitate conduction of systematic reviews and meta-analyses, and better inform clinical practice. PERSPECTIVE: This review of chronic and recurrent pediatric pain trials demonstrates inadequacies in the reporting quality of key features specifically important to pediatric populations. It provides recommendations that address these shortcomings to promote continued efforts toward improving the quality of the design and publication of future pediatric clinical pain trials.
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Ensayos Clínicos como Asunto , Metaanálisis en Red , Evaluación de Resultado en la Atención de Salud , Manejo del Dolor , Dolor , Pediatría , Proyectos de Investigación , Niño , HumanosRESUMEN
Sleep plays a pivotal role in children and adolescents with headache. Although several sleep measures exist, no developed measures target the sleep issues common in pediatric patients with headache. The Sleep Hygiene Inventory for Pediatrics (SHIP) was developed for clinical purposes to fulfill this need. The aim of this study was to validate the SHIP for potential research applications in a sample of 1078 children and adolescents (7-17 years) with a primary headache diagnosis. Measure validation included assessments of internal consistency, construct validity, and criterion validity. The SHIP demonstrated strong internal consistency (Cronbach α = 0.84). The SHIP differentiated well between participants for whom sleep was and was not a clinical concern ( P < .001; d =1.65), and was positively correlated with anxiety, depression, and disability. These analyses suggest that the SHIP is a psychometrically strong and valid assessment of sleep habits in pediatric patients with headache.
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Trastornos de Cefalalgia/diagnóstico , Higiene del Sueño , Adolescente , Ansiedad , Niño , Depresión , Evaluación de la Discapacidad , Femenino , Trastornos de Cefalalgia/fisiopatología , Trastornos de Cefalalgia/psicología , Humanos , Masculino , Padres , Pediatría/métodos , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
In chronic pain, a number of brain regions involved in emotion (e.g., amygdala, hippocampus, nucleus accumbens, insula, anterior cingulate, and prefrontal cortex) show significant functional and morphometric changes. One phenotypic manifestation of these changes is pain-related fear (PRF). PRF is associated with profoundly altered behavioral adaptations to chronic pain. For example, patients with a neuropathic pain condition known as complex regional pain syndrome (CRPS) often avoid use of and may even neglect the affected body area(s), thus maintaining and likely enhancing PRF. These changes form part of an overall maladaptation to chronic pain. To examine fear-related brain circuit alterations in humans, 20 pediatric patients with CRPS and 20 sex- and age-matched healthy controls underwent functional magnetic resonance imaging (fMRI) in response to a well-established fearful faces paradigm. Despite no significant differences on self-reported emotional valence and arousal between the two groups, CRPS patients displayed a diminished response to fearful faces in regions associated with emotional processing compared to healthy controls. Additionally, increased PRF levels were associated with decreased activity in a number of brain regions including the right amygdala, insula, putamen, and caudate. Blunted activation in patients suggests that (a) individuals with chronic pain may have deficits in cognitive-affective brain circuits that may represent an underlying vulnerability or consequence to the chronic pain state; and (b) fear of pain may contribute and/or maintain these brain alterations. Our results shed new light on altered affective circuits in patients with chronic pain and identify PRF as a potentially important treatment target.
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There are reports that complex regional pain syndrome, type I (reflex sympathetic dystrophy; CRPS-I/RSD) can spread from the initial site of presentation, but there are no detailed descriptions of the pattern(s) of such spread. We describe a retrospective analysis of 27 CRPS-I/RSD patients who experienced a significant spread of pain. Three patterns of spread were identified. 'Contiguous spread (CS)' was noted in all 27 cases and was characterized by a gradual and significant enlargement of the area affected initially. 'Independent spread (IS)' was noted in 19 patients (70%) and was characterized by the appearance of CRPS-I in a location that was distant and non-contiguous with the initial site (e.g. CRPS-I/RSD appearing first in a foot, then in a hand). 'Mirror-image spread (MS)' was noted in four patients (15%) and was characterized by the appearance of symptoms on the opposite side in an area that closely matched in size and location the site of initial presentation. Only five patients (19%) suffered from CS alone; 70% also had IS, 11% also had MS, and one patient had all three kinds of spread. Our results suggest that CRPS-I/RSD spread may not be a unitary phenomenon. In some it may be due to a local spread of pathology (CS); in others it may be a consequence of a generalized susceptibility (IS). In the MS case, spread may be due to abnormal neural functioning spreading via commissural pathways. Alternatively, we discuss the possibility that all three kinds of spread may be due to aberrant CNS regulation of neurogenic inflammation.
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Distrofia Simpática Refleja/fisiopatología , Adulto , Femenino , Pie/fisiopatología , Mano/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Distrofia Simpática Refleja/etiología , Estudios Retrospectivos , Heridas y Lesiones/fisiopatologíaRESUMEN
Pediatric complex regional pain syndrome (P-CRPS) offers a unique model of chronic neuropathic pain as it either resolves spontaneously or through therapeutic interventions in most patients. Here we evaluated brain changes in well-characterized children and adolescents with P-CRPS by measuring resting state networks before and following a brief (median = 3 weeks) but intensive physical and psychological treatment program, and compared them to matched healthy controls. Differences in intrinsic brain networks were observed in P-CRPS compared to controls before treatment (disease state) with the most prominent differences in the fronto-parietal, salience, default mode, central executive, and sensorimotor networks. Following treatment, behavioral measures demonstrated a reduction of symptoms and improvement of physical state (pain levels and motor functioning). Correlation of network connectivities with spontaneous pain measures pre- and post-treatment indicated concomitant reductions in connectivity in salience, central executive, default mode and sensorimotor networks (treatment effects). These results suggest a rapid alteration in global brain networks with treatment and provide a venue to assess brain changes in CRPS pre- and post-treatment, and to evaluate therapeutic effects.
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Encéfalo/fisiopatología , Red Nerviosa/fisiopatología , Distrofia Simpática Refleja/fisiopatología , Adolescente , Mapeo Encefálico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , DescansoAsunto(s)
Enfermedades Gastrointestinales/tratamiento farmacológico , Síndrome del Colon Irritable/tratamiento farmacológico , Vías Aferentes/efectos de los fármacos , Vías Aferentes/fisiopatología , Analgésicos/uso terapéutico , Anticonvulsivantes/uso terapéutico , Antidepresivos/uso terapéutico , Niño , Enfermedades Gastrointestinales/psicología , Humanos , Hipnóticos y Sedantes/uso terapéutico , Síndrome del Colon Irritable/psicología , DolorRESUMEN
Pediatric patients with chronic tension-type headaches often experience significant school impairment. Although some improve after treatment with a neurologist, many require more comprehensive treatment. The authors examined whether school functioning and attendance improved after a multidisciplinary evaluation focusing on a return to functioning despite headaches. They also examined whether patients' headaches improved. Participants were 47 adolescents ages 12-17, most of whom had not responded to past neurological treatment. Adolescents completed the PedsQL School Functioning Scale at evaluation, 2-3 months later, and again 6 months after evaluation. Information regarding headache frequency, severity and duration, and school attendance was obtained from medical records. Using repeated measures analyses of variance, the authors found that school functioning and attendance improved significantly from evaluation to follow-up, as did headache frequency and duration. An emphasis on returning to functioning can help patients with chronic, difficult-to-treat tension-type headaches improve in their school functioning and experience fewer, shorter headaches.
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Absentismo , Conducta Cooperativa , Comunicación Interdisciplinaria , Estudiantes/psicología , Estudiantes/estadística & datos numéricos , Cefalea de Tipo Tensional/epidemiología , Cefalea de Tipo Tensional/terapia , Adolescente , Niño , Enfermedad Crónica , Escolaridad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Calidad de Vida/psicología , Cefalea de Tipo Tensional/psicología , Centros de Atención Terciaria , Resultado del TratamientoRESUMEN
Neuropathic pain is relatively uncommon in children. Although some syndromes closely resemble those found in adults, the incidence and course of the condition can vary substantially in children, depending on developmental status and contextual factors. There are some neuropathic pain syndromes that are rare and relatively unique to the pediatric population. This article discusses the array of neuropathic pain conditions in children and available treatment strategies. Data are limited by small numbers and few randomized controlled trials. Research and clinical implications are discussed.
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Analgésicos/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Neuralgia/tratamiento farmacológico , Neuralgia/etiología , Analgésicos/administración & dosificación , Analgésicos/efectos adversos , Analgésicos Opioides/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Niño , Servicios de Salud del Niño/organización & administración , Protección a la Infancia , Síndromes de Dolor Regional Complejo/complicaciones , Neuropatías Diabéticas/complicaciones , Relación Dosis-Respuesta a Droga , Medicina Basada en la Evidencia , Humanos , Neuralgia/clasificación , Neuralgia Posherpética/complicaciones , Dolor/tratamiento farmacológico , Dolor/etiología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel alpha(2)-delta ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.