Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls.

OBJECTIVES: Excessive fecal bile acids in adults have been associated with diarrhea-predominant irritable bowel syndrome (IBS-D), but their role in pediatric IBS-D is unknown. Serum markers including 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor-19 (FGF-19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48-hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF-19 and 48FBA in a pediatric population, to compare measurements in IBS-D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS-D. METHODS: Using a cross-sectional design, 26 patients with IBS-D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF-19 and 48FBA were obtained. Participants completed a 7-day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations. RESULTS: Mean age was 14.7 ±â€Š2.5 years (42.3% female) in IBS-D and 12.6 ±â€Š2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF-19 (r = -0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF-19 (P = 0.1), or 48FBA (P = 0.5) between IBS-D and HC groups; however, 20% of IBS-D patients had elevated C4 and 28% had low FGF-19 values.Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002). CONCLUSIONS: Correlations of C4 with 48FBA and FGF-19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS-D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS-D.

Childhood Functional Gastrointestinal Disorders: Neonate/Toddler.

In 2006, a consensus concerning functional gastrointestinal intestinal disorders (FGIDs) in infants and toddlers was described. At that time little evidence regarding epidemiology, pathophysiology, diagnostic work-up, treatment strategies and follow-up was available. Consequently the criteria for the clinical entities were more experience than evidence based. In the past decade, new insights have been gained in the different FGIDs in these age groups. Based on those, further revisions have been made to the criteria. The description of infant colic has been expanded to include criteria for the general pediatrician and specific criteria for researchers. The greatest change was the addition of a paragraph regarding the neurobiology of pain in infants and toddlers, including the understanding of the neurodevelopment of nociception and of the wide array of factors that may impact the pain experience.

Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society-American Academy of Pain Medicine Pain Taxonomy Diagnostic Criteria for Acute Needle Pain.

Needle procedures are among the most common causes of pain and distress for individuals seeking health care. While needle pain is especially problematic for children needle pain and associated fear also has significant impact on adults and can lead to avoidance of appropriate medical care. Currently there is not a standard definition of needle pain. A taxonomy, or classification system, for acute needle pain would aid research efforts and enhance clinical care. To meet this need, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the U.S. Food and Drug Administration, the American Pain Society, and the American Academy of Pain Medicine formed the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society-American Academy of Pain Medicine Pain Taxonomy initiative. One of the goals of this initiative was to develop taxonomies for acute pain disorders, including needle pain. To accomplish this, a working group of experts in needle pain was convened. Based on available literature and expert opinion, the working group used a 5-dimenional structure (diagnostic criteria, common features, modulating factors, impact and/or functional consequences, and putative mechanisms) to develop an acute pain taxonomy that is specific needle pain. As part of this, a set of 4 diagnostic criteria, with 2 modifiers to account for the influence of needle associated fear, are proposed to define the types of acute needle pain. PERSPECTIVE: This article presents a taxonomy for acute needle pain. This taxonomy could help to standardize definitions of acute pain in clinical studies of patients undergoing needle procedures.

Do children with sickle cell disease receive disparate care for pain in the emergency department?

BACKGROUND: There may be disparities in pain management practice in the emergency department (ED) for sickle cell disease patients (SCD) with vaso-occlusive episodes (VOE). OBJECTIVES: To compare pain management practice for children who presented to the ED with VOE to those with isolated long bone fractures (LBF). METHODS: Children who presented with a VOE or a LBF to a children's hospital ED during 2005 were included. A retrospective medical chart review was conducted for each patient visit. Data collected included demographics, pain scores, time from triage to analgesia, and analgesic intervention. RESULTS: Seventy-seven patients with SCD had 152 visits to the ED for pain, and 219 patients had 221 visits for LBF. Fifty-five patients (108 visits) with SCD and 123 patients (124 visits) with LBF received opiates. Subsequent analysis was done on these groups. Patients with SCD were older, less likely to be male and more likely to be African-American than the LBF group. Patients with SCD had higher triage pain scores (7.7 ± 2.5 vs. 6.7 ± 3.0, p = 0.005) and spent less time in the waiting room (7.4 ± 9.0 vs. 12.1 ± 26.8 min, p = 0.10), were given higher initial opiate doses (0.09 ± 0.03 vs. 0.07 ± 0.03 mg/kg morphine, p < 0.001); however, time from triage to analgesic intervention did not differ (69.0 ± 42.6 vs. 70.4 ± 57.1 min, p = 0.92). CONCLUSIONS: No disparities in care for children with sickle cell pain were identified. More timely administration of opiates needs to be encouraged, assuming other factors such as time of day, ED census, and acuity permit.

Perceptions of Pain Treatment in Pediatric Patients With Functional Gastrointestinal Disorders.

OBJECTIVES: Individual understanding of and expectations for chronic pain treatment can influence treatment adherence and thus success, but little is known about these critical factors in parents and children presenting with pain-predominant functional gastrointestinal disorders. The aim of this study was to identify parent and patient understanding of pain-predominant functional gastrointestinal disorders, expectations for treatment, and interventions utilized before presenting to a multidisciplinary clinic. MATERIALS AND METHODS: This was a prospective study of patients evaluated in a Multidisciplinary Functional Abdominal Pain Program. Before the clinic visit, parents and patients completed questionnaires regarding their understanding of chronic pain, perceptions of abdominal pain contributors, expectations regarding treatment, and identification of previous interventions utilized. RESULTS: Participants were knowledgeable regarding the biology of chronic pain. Perceptions of contributors to abdominal pain included a sensitive stomach, general stress, and nerves/worry. Most had attempted to treat their pain with medication, exercise or physical therapy, or a psychological treatment. Participants reported that receiving a definite diagnosis would be the most helpful intervention, followed by psychological treatment. DISCUSSION: Participants were knowledgeable regarding chronic pain, but still indicated that receiving a definite diagnosis would be the most helpful intervention. Most had tried multiple interventions and did not believe that further medication, testing, or surgery would solve their pain. Instead, parents presenting at this Functional Abdominal Pain Program appeared most hopeful about the benefits of multidisciplinary treatment approaches including psychological interventions, a focus on activity and functioning, and complementary and alternative medicine interventions.

A novel needle-free powder lidocaine delivery system for rapid local analgesia.

OBJECTIVE: To determine the analgesic effect and tolerability of a novel needle-free powder lidocaine delivery system in children undergoing venipuncture. STUDY DESIGN: In this double-blind, placebo-controlled, single-center trial, 306 children age 3 to 18 years were randomized to receive a needle-free powder lidocaine delivery system or matching sham placebo at the back of the hand 2 to 3 minutes before venipuncture. Venipuncture pain was self-reported using the Wong-Baker FACES scale (in 3- to 12-year-olds) and a 100-mm visual analog scale (in 8- to 18-year-olds). Safety was assessed by adverse events, investigator skin site assessments, and children's self-report of the administration comfort of study treatments. Effect sizes were compared by 2-sample t test and Glass's Delta approach. RESULTS: Subjects receiving the needle-free powder lidocaine delivery system exhibited mean pain reductions (effect size) of 33% to 46% relative to sham placebo. Pain reductions were statistically significant for all ages combined and also for the youngest and oldest age strata. Self-reported administration comfort levels were similar in the active system and sham placebo groups. Incidences of adverse events and dermal reactions were low; the most common dermal reaction was mild erythema. CONCLUSIONS: The needle-free powder lidocaine delivery system was well tolerated and provided effective local analgesia when administered 2 to 3 minutes before venipuncture.

Retrospective evaluation of pain assessment and treatment for acute vasoocclusive episodes in children with sickle cell disease.

BACKGROUND: This study was conducted to assess the care of pediatric patients hospitalized for sickle cell disease-related vasoocclusive episodes (VOE). The aim of this research was to illustrate the course of pain scores and methods of therapeutic intervention during hospitalization. PROCEDURE: Retrospective medical chart reviews were conducted to collect pain assessment and management data about children hospitalized during a 2-year period at an urban children's hospital. T tests and Chi-square analyses were used to identify differences in demographic variables, pain scores and opiate utilization. RESULTS: There were 59 children with 134 hospitalizations for VOE in a 2-year period. 50.8% of the patients were male; the mean age was 11.5 +/- 4.9 years. The average length of hospitalization was 4.6 +/- 2.7 days (range 1-19 days). Older patients stayed in the hospital significantly longer than younger patients (P = 0.002). Pain scores remained in the moderate to severe range (> or =5 out of 10) for many days in the majority of patients. Results failed to reveal significant differences in pain scores and opiate utilization between patients who had short versus extended hospitalizations, and for those patients with frequent versus infrequent hospitalizations for pain. CONCLUSIONS: Despite opiate dosing within recommended guidelines, mean pain scores remain in the moderate to severe range for several days following hospitalization for VOE. Future research should explore the factors which influence pain scores, as well as improved pain assessment and management techniques.

Microstructural White Matter Abnormalities in the Dorsal Cingulum of Adolescents with IBS.

Alterations in fractional anisotropy (FA) have been considered to reflect microstructural white matter (WM) changes in disease conditions; however, no study to date has examined WM changes using diffusion tensor imaging (DTI) in adolescents with irritable bowel syndrome (IBS). The objective of the present study was two-fold: (1) to determine whether differences in FA, and other non-FA metrics, were present in adolescents with IBS compared to healthy controls using whole-brain, region of interest (ROI)-restricted tract-based spatial statistics (TBSS) and canonical ROI DTI analyses for the cingulum bundle, and (2) to determine whether these metrics were related to clinical measures of disease duration and pain intensity in the IBS group. A total of 16 adolescents with a Rome III diagnosis of IBS (females = 12; mean age = 16.29, age range: 11.96-18.5 years) and 16 age- and gender-matched healthy controls (females = 12; mean age = 16.24; age range: 11.71-20.32 years) participated in this study. Diffusion-weighted images were acquired using a Siemens 3-T Trio Tim Syngo MRI scanner with a 32-channel head coil. The ROI-restricted TBSS and canonical ROI-based DTI analyses revealed that adolescents with IBS showed decreased FA in the right dorsal cingulum bundle compared to controls. No relationship between FA and disease severity measures was found. Microstructural WM alterations in the right dorsal cingulum bundle in adolescents with IBS may reflect a premorbid brain state or the emergence of a disease-driven process that results from complex changes in pain- and affect-related processing via spinothalamic and corticolimbic pathways.

Abdominal Pain, the Adolescent and Altered Brain Structure and Function.

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in adolescents with IBS. It is possible such changes will be responsive to therapeutic intervention and may be useful as potential markers of disease progression or reversal.

Perspectives on the clinical significance of functional pain syndromes in children.

Functional pain syndromes (FPS) characterize a subset of individuals who experience pain and related symptoms and disability without clear structural or disease etiology. In the pediatric population, FPS hold high clinical importance due to significant prevalence rates and potential to persist into adulthood. Although extensive research has been executed to disambiguate FPS, the syndromes that fall within its spectrum remain conceptually complex and sometimes ill-defined. This paper provides an overview of available research on the classification and multifaceted etiology of FPS in youth and their effects on interpersonal, psychological, and familial function. Vital aspects of a successful multidisciplinary approach to treating this population are described; however, it is evident that future research requires more longitudinal studies.

Persistent pain in chronically ill children without detectable disease activity.

Children with organic diseases may experience persistent pain in the presence of controlled disease, as evidenced by little or no measurable disease activity or inflammation. Historically, dualistic definitions of pain have informed standard diagnostic approaches to persistent pain; aggressive investigation and treatment targeting underlying disease, even in the absence of evidence indicating disease escalation. Evidence across disease populations, in children with inflammatory bowel disease, sickle cell disease, and juvenile idiopathic arthritis indicates that persistent pain in these conditions may be better conceptualized as functional in nature, potentially resulting from disordered somatosensory processing including central sensitization. Applying a biopsychosocial understanding of persistent pain and multidisciplinary functional pain management strategies may lead to improved health outcomes.

Educational outreach to reduce immunization pain in office settings.

OBJECTIVE: The goal was to examine the impact of a teaching module on immunization pain reduction practices in pediatric offices 1 and 6 months after the intervention. METHODS: Fourteen practices were selected randomly to receive a 1-hour teaching session on immunization pain reduction techniques, and 13 completed the study. Before the intervention, telephone interviews were conducted with parents concerning their children's recent immunization experiences. At 1 and 6 months after the intervention, parents of children who had recent immunizations were interviewed by using the same questionnaires. Clinicians also were surveyed at baseline and at 6 months. RESULTS: A total of 839 telephone interviews and 92 clinician surveys were included. Significant changes from baseline were identified at 1 and 6 months after the intervention. At 1 month, parents were more likely to report receiving information (P = .04), using strategies to reduce pain (P < .01), learning something new (P < .01), using a ShotBlocker (P < .01), using sucrose (P < .01), and having higher levels of satisfaction (P = .015). At 6 months, all rates remained significantly higher than baseline findings (all P < .01) except for satisfaction. Clinician surveys revealed significant increases in the use of longer needles, sucrose, pinwheels, focused breathing, and ShotBlockers at 6 months. CONCLUSIONS: A 1-hour teaching session had measurable effects on the use of pain-reducing strategies at 1 and 6 months after the intervention. This research supports the hypothesis that small-group teaching sessions at the site of care can be associated with changes in practice behaviors.