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.

Multidisciplinary Treatment Reduces Pain and Increases Function in Children With Functional Gastrointestinal Disorders.

Functional gastrointestinal disorders (FGIDs) are common in children and adolescents, frequently resulting in extensive testing, school absenteeism, disability, and poor quality of life.1-3 FGIDs result from a complex interplay between genetic predisposition, biological triggers, and psychosocial triggers, and are best explained by the biopsychosocial model.1 Although this implies the necessity of multidisciplinary treatment, studies showing the efficacy of such an intervention are lacking. We describe the outcome of children with severe FGIDs treated in a multidisciplinary program.

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.

Antidepressants for chronic non-cancer pain in children and adolescents.

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Antidepressants have been used in adults for pain relief and pain management since the 1970s. The clinical impression from extended use over many years is that antidepressants are useful for some neuropathic pain symptoms, and that effects on pain relief are divorced and different from effects on depression; for example, the effects of tricyclic antidepressants on pain may occur at different, and often lower, doses than those on depression. Amitriptyline is one of the most commonly used drugs for treating neuropathic pain in the UK. OBJECTIVES: To assess the analgesic efficacy and adverse events of antidepressants used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any antidepressant with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed the evidence using GRADE and created three 'Summary of findings' tables. MAIN RESULTS: We included four studies with a total of 272 participants (6 to 18 years of age) who had either chronic neuropathic pain, complex regional pain syndrome type 1, irritable bowel syndrome, functional abdominal pain, or functional dyspepsia. All of the studies were small. One study investigated amitriptyline versus gabapentin (34 participants), two studies investigated amitriptyline versus placebo (123 participants), and one study investigated citalopram versus placebo (115 participants). Due to a lack of available data we were unable to complete any quantitative analysis.Risk of bias for the four included studies varied, due to issues with randomisation and allocation concealment (low to unclear risk); blinding of participants, personnel, and outcome assessors (low to unclear risk); reporting of results (low to unclear risk); and size of the study populations (high risk). We judged the remaining domains, attrition and other potential sources of bias, as low risk of bias. Primary outcomesNo studies reported our primary outcomes of participant-reported pain relief of 30% or greater or 50% or greater (very low-quality evidence).No studies reported on Patient Global Impression of Change (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) as very low. We downgraded the quality of the evidence by three levels to very low because there was no evidence to support or refute. Secondary outcomesAll studies measured adverse events, with very few reported (11 out of 272 participants). All but one adverse event occurred in the active treatment groups (amitriptyline, citalopram, and gabapentin). Adverse events in all studies, across active treatment and comparator groups, were considered to be a mild reaction, such as nausea, dizziness, drowsiness, tiredness, and abdominal discomfort (very low-quality evidence).There were also very few withdrawals due to adverse events, again all but one from the active treatment groups (very low-quality evidence).No serious adverse events were reported across any of the studies (very low-quality evidence).There were few or no data for our remaining secondary outcomes (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) for these secondary outcomes as very low. We downgraded the quality of the evidence by three levels to very low due to too few data and the fact that the number of events was too small to be meaningful. AUTHORS' CONCLUSIONS: We identified only a small number of studies with small numbers of participants and insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of antidepressants to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.There is evidence from adult randomised controlled trials that some antidepressants, such as amitriptyline, can provide some pain relief in certain chronic non-cancer pain conditions.There is no evidence from randomised controlled trials to support or refute the use of antidepressants to treat chronic non-cancer pain in children or adolescents.

Antiepileptic drugs for chronic non-cancer pain in children and adolescents.

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as importantWe designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can occur in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) relating to genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and for other unknown reasons.Antiepileptic (anticonvulsant) drugs, which were originally developed to treat convulsions in people with epilepsy, have in recent years been used to provide pain relief in adults for many chronic painful conditions and are now recommended for the treatment of chronic pain in the WHO list of essential medicines. Known side effects of antiepileptic drugs range from sweating, headache, elevated temperature, nausea, and abdominal pain to more serious effects including mental or motor function impairment. OBJECTIVES: To assess the analgesic efficacy and adverse events of antiepileptic drugs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews as well as online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, by any route, treating chronic non-cancer pain in children and adolescents, comparing any antiepileptic drug with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods if data were available. We assessed the evidence using GRADE and created two 'Summary of findings' tables. MAIN RESULTS: We included two studies with a total of 141 participants (aged 7 to 18 years) with chronic neuropathic pain, complex regional pain syndrome type 1 (CRPS-I), or fibromyalgia. One study investigated pregabalin versus placebo in participants with fibromyalgia (107 participants), and the other study investigated gabapentin versus amitriptyline in participants with CRPS-I or neuropathic pain (34 participants). We were unable to perform any quantitative analysis.Risk of bias for the two included studies varied, due to issues with randomisation (low to unclear risk), blinding of outcome assessors (low to unclear risk), reporting bias (low to unclear risk), the size of the study populations (high risk), and industry funding in the 'other' domain (low to unclear risk). We judged the remaining domains of sequence generation, blinding of participants and personnel, and attrition as low risk of bias. Primary outcomesOne study (gabapentin 900 mg/day versus amitriptyline 10 mg/day, 34 participants, for 6 weeks) did not report our primary outcomes (very low-quality evidence).The second study (pregabalin 75 to 450 mg/day versus placebo 75 to 450 mg/day, 107 participants, for 15 weeks) reported no significant change in pain scores for pain relief of 30% or greater between pregabalin 18/54 (33.3%), and placebo 16/51 (31.4%), P = 0.83 (very low-quality evidence). This study also reported Patient Global Impression of Change, with the percentage of participants feeling "much or very much improved" with pregabalin 53.1%, and placebo 29.5% (very low-quality evidence).We downgraded the evidence by three levels to very low for one of two reasons: due to the fact that there was no evidence to support or refute the use of the intervention, or that there were too few data and the number of events was too small to be meaningful. Secondary outcomesIn one small study, adverse events were uncommon: gabapentin 2 participants (2 adverse events); amitriptyline 1 participant (1 adverse event) (6-week trial). The second study reported a higher number of adverse events: pregabalin 38 participants (167 adverse events); placebo 34 participants (132 adverse events) (15-week trial) (very low-quality evidence).Withdrawals due to adverse events were infrequent in both studies: pregabalin (4 participants), placebo (4 participants), gabapentin (2 participants), and amitriptyline (1 participant) (very low-quality evidence).Serious adverse events were reported in both studies. One study reported only one serious adverse event (cholelithiasis and major depression resulting in hospitalisation in the pregabalin group) and the other study reported no serious adverse events (very low-quality evidence).There were few or no data for our remaining secondary outcomes (very low-quality evidence).We downgraded the evidence by three levels to very low due to too few data and the fact that the number of events was too small to be meaningful. AUTHORS' CONCLUSIONS: This review identified only two small studies, with insufficient data for analysis.As we could undertake no meta-analysis, we were unable to comment about efficacy or harm from the use of antiepileptic drugs to treat chronic non-cancer pain in children and adolescents. Similarly, we could not comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.We know from adult randomised controlled trials that some antiepileptics, such as gabapentin and pregabalin, can be effective in certain chronic pain conditions.We found no evidence to support or refute the use of antiepileptic drugs to treat chronic non-cancer pain in children and adolescents.

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.

From One Pain to Many: The Emergence of Overlapping Pains in Children and Adolescents.

OBJECTIVES: The objective of this study was to compare children and adolescents with overlapping chronic pains (OCP) to those with single chronic pains (SCP) among youth presenting in specialized clinical settings, in an effort to identify potential risk factors for developing overlapping pains. METHODS: A total of 1235 youth ages 8 to 18 seen in a tertiary care multidisciplinary pain clinic or a multidisciplinary headache clinic completed self-report measures of pain, disability, psychological functioning and clinical history and characteristics at the time of initial clinic visit. Information was captured in a chronic pain data repository and accessed for the current study. RESULTS: Subsequent pain symptoms developed on average 11.9 months (SD=24.5 mo) after onset of the first pain symptom. Compared with patients with SCP, patients with OCP report more medical comorbidity, more developmental issues, and poorer current sleep and school functioning. They also scored significantly higher than patients with SCP on self-reported functional disability, pain catastrophizing, fear of pain, depression, anxiety, and psychological stress and lower quality of life (all Ps<0.001). In multivariate analysis, variables most strongly associated with presenting with OCP were age (odds ratio [OR]: 1.1, P<0.001), having a clinically significant high functional disability (OR: 1.4, P=0.3), and low quality of life (OR: 2.5, P<0.001). DISCUSSION: Given their tendency toward more psychological and medical comorbidities, patients with OCP may require more intense and diverse treatment approaches. Some early life experiences may be a risk factor for development of OCP. Longitudinal studies are needed to fully evaluate the heightened risk for OCP associated with some of these factors.

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.

Pharmacological interventions for chronic pain in children: an overview of systematic reviews.

We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with CNCP or CCRP. We extracted the review characteristics and primary outcomes of ≥30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with CNCP or CCRP. Seven of those 23 reviews included 6 trials that involved children with CNCP. There were no randomised controlled trials in reviews relating to reducing pain in CCRP. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low, and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42018086900.

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.

The role of emotion regulation in chronic pain: A systematic literature review.

OBJECTIVE: Emotion regulation (ER) includes a set of cognitive and attentional processes used to change or maintain emotional state. A small but growing body of research suggests that maladaptive ER might be a risk factor for the development of chronic pain. This review aims to summarize existing literature on the association between ER and chronic pain, and to determine whether the construct of ER may further enhance our understanding of the risk and protective factors that may contribute to the onset and maintenance of chronic pain. METHODS: A systematic search was conducted using the search terms "chronic pain" and "emotion regulation." Studies that measured both constructs across all age groups were included. RESULTS: We found 15 studies that met our inclusion criteria. Nine studies were completed within the last five years, suggesting that the evaluation of ER as it relates to pain is a new line of research. Studies that measured "response-focused" ER found associations between maladaptive ER and pain. Studies that measured "antecedent-focused" ER strategies were less likely to show a direct association with pain. CONCLUSION: Maladaptive response-focused ER may be an important risk factor in the development and maintenance of chronic pain, as it is associated with pain and psychological comorbidities. Adding ER to chronic pain investigations may help to further explain individual differences in the risk and protective mechanisms that are known to influence chronic pain. Importantly, this line of research has potential to directly inform future interventions for patients with chronic pain.

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.

Pediatric Pain Screening Tool: rapid identification of risk in youth with pain complaints.

Moderate to severe chronic pain is a problem for 1.7 million children, costing $19.5 billion dollars annually in the United States alone. Risk-stratified care is known to improve outcomes in adults with chronic pain. However, no tool exists to stratify youth who present with pain complaints to appropriate interventions. The Pediatric Pain Screening Tool (PPST) presented here assesses prognostic factors associated with adverse outcomes among youth and defines risk groups to inform efficient treatment decision making. Youth (n = 321, ages 8-18, 90.0% Caucasian, 74.8% female) presenting for multidisciplinary pain clinic evaluation at a tertiary care center participated. Of these, 195 (61.1%) participated at 4-month follow-up. Participants completed the 9-item PPST in addition to measures of functional disability, pain catastrophizing, fear of pain, anxiety, and depressive symptoms. Sensitivity and specificity for the PPST ranged from adequate to excellent, with regard to significant disability (78%, 68%) and high emotional distress (81%, 63%). Participants were classified into low- (11%), medium- (32%), and high- (57%) risk groups. Risk groups did not significantly differ by pain diagnosis, location, or duration. Only 2% to 7% of patients who met reference standard case status for disability and emotional distress at 4-month follow-up were classified as low risk at baseline, whereas 71% to 79% of patients who met reference standard case status at follow-up were classified as high risk at baseline. A 9-item screening tool identifying factors associated with adverse outcomes among youth who present with pain complaints seems valid and provides risk stratification that can potentially guide effective pain treatment recommendations in the clinic setting.