Heterogeneity in Pancreatitis: Recognizing Heterogeneity and Its Role in the Management of Pancreatitis. Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

Both the clinical management and study of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) is complicated by significant heterogeneity in the etiology, mechanisms, symptoms, and complications of pancreatitis. The National Institutes of Diabetes and Digestive and Kidney Disease (NIDDK) recently convened a workshop to address current knowledge and knowledge gaps in the field. Preclinical models that better replicate human disease are important for development of new therapies.

Radiation of pain: psychophysical evidence for a population coding mechanism in humans.

The spread of pain across body locations remains poorly understood but may provide important insights into the encoding of sensory features of noxious stimuli by populations of neurons. In this psychophysical experiment, we hypothesized that more intense noxious stimuli would lead to spread of pain, but more intense light stimuli would not produce perceptual radiation. Fifty healthy volunteers (27 females, 23 males, ages 14-44 years) participated in this study wherein noxious stimuli (43, 45, 47, and 49°C) were applied to glabrous (hand) and hairy skin (forearm) skin with 5-second and 10-second durations.

Neurophysiology of Resilience in Juvenile Fibromyalgia.

Objective: Juvenile fibromyalgia (JFM) is a chronic pain syndrome predominantly affecting adolescent girls. Resilience may be a protective factor in coping with pain, reducing affective burden, and promoting positive outlooks. Brain regions affected in JFM overlap with those linked to resilience, particularly in the default-mode network (DMN).

Radiation of pain: Psychophysical evidence for a population coding mechanism in humans.

The spread of pain across body locations remains poorly understood but may provide important insights into the encoding of sensory features of noxious stimuli by populations of neurons. In this psychophysical experiment, we hypothesized that more intense noxious stimuli would lead to spread of pain, but more intense light stimuli would not produce perceptual radiation. Fifty healthy volunteers (27 females, 23 males, ages 14-44) participated in this study wherein noxious stimuli (43, 45, 47 and 49°C) were applied to glabrous (hand) and hairy skin (forearm) skin with 5s and 10s durations.

Study protocol for a pilot clinical trial to understand neural mechanisms of response to a psychological treatment for pain and anxiety in pediatric functional abdominal pain disorders (FAPD).

Background: Functional abdominal pain disorders (FAPD) are the most common chronic pain conditions of childhood and are made worse by co-occurring anxiety. Our research team found that the Aim to Decrease Pain and Anxiety Treatment (ADAPT), a six-session coping skills program using cognitive behavioral therapy strategies, was effective in improving pain-related symptoms and anxiety symptoms compared to standard care. In follow-up, this current randomized clinical trial (RCT) aims to test potential neural mechanisms underlying the effect of ADAPT.

Weak Relationships Between Psychological Factors and Experimental Pain Outcomes in Pain-Free Individuals: An Aggregate Analysis of 8 Studies.

Although psychological factors such as anxiety, depression, and pain catastrophizing are known to influence pain outcomes in chronic pain populations, there are mixed results regarding whether they influence experimental pain outcomes in pain-free individuals. The objectives of this study were to determine the associations between psychological factors and experimental pain outcomes in pain-free adolescents and adults. Relationships between anxiety, depression, and pain catastrophizing and experimental pain outcomes across 8 different studies (total N = 595) were examined in different populations of pain-free adult and adolescent participants.

Denoising task-related fMRI: Balancing noise reduction against signal loss.

Preprocessing fMRI data requires striking a fine balance between conserving signals of interest and removing noise. Typical steps of preprocessing include motion correction, slice timing correction, spatial smoothing, and high-pass filtering. However, these standard steps do not remove many sources of noise.

Reduced Cortico-Cortical Resting-State Connectivity in Sensory Systems Related to Bodily Pain in Juvenile Fibromyalgia.

Objective: Juvenile-onset fibromyalgia (JFM) is a paradigmatic chronic pain condition for which the underlying neurobiological substrates are poorly understood. This study examined, for the first time, data-driven resting-state functional connectivity (rsFC) alterations in 37 female adolescents with JFM compared with 43 healthy female adolescents and identified associations with bodily pain.

Methods: Whole-brain voxel-wise rsFC alterations were assessed using the intrinsic connectivity contrast, a measure of node centrality at each voxel, and seed-based analyses for interpretability.

Tolerability of transcranial magnetic stimulation language mapping in children.

Objective: Transcranial Magnetic Stimulation (TMS) has emerged as a viable non-invasive method for mapping language networks. Little is known about the tolerability of transcranial magnetic stimulation language mapping in children.

Methods: Children aged 5-18 years underwent bilateral language mapping using repetitive transcranial magnetic stimulation (rTMS) to target 33 sites/hemisphere.

Communication of pain intensity and unpleasantness through magnitude ratings: Influence of scale type, but not gender of the participant.

Background: A critical aspect for most human pain research is the ability of participants to communicate their first-person, experiential perspective to a third-person observer. This communication is frequently accomplished via pain ratings. The scale type can influence the communication of pain experiences and can contribute to gender differences in pain.

Augmented pain-evoked primary sensorimotor cortex activation in adolescent girls with juvenile fibromyalgia.

Juvenile fibromyalgia (JFM) is a chronic widespread pain condition that primarily affects adolescent girls. Previous studies have found increased sensitivity to noxious pressure in adolescents with JFM. However, the underlying changes in brain systems remain unclear.

Spatial Tuning in Nociceptive Processing Is Driven by Attention.

When the source of nociception expands across a body area, the experience of pain increases due to the spatial integration of nociceptive information. This well-established effect is called spatial summation of pain (SSp) and has been the subject of multiple investigations. Here, we used cold-induced SSp to investigate the effect of attention on the spatial tuning of nociceptive processing.

The distributed nociceptive system: a novel framework for understanding pain.

Our current understanding of central nervous system mechanisms supporting the experience of pain remains remarkably limited and produces substantial challenges when seeking to better diagnose and treat chronic pain. A new conceptual framework - The Distributed Nociceptive System - emphasizes system-level aspects of nociceptive processing by incorporating population coding and distributed process. The Distributed Nociceptive System provides a structure for understanding complex spatial aspects of chronic pain and provides a clear rationale for the further development of multi-disciplinary treatments for chronic pain.

Dissociation between individual differences in self-reported pain intensity and underlying fMRI brain activation.

Pain is an individual experience. Previous studies have highlighted changes in brain activation and morphology associated with within- and interindividual pain perception. In this study we sought to characterize brain mechanisms associated with between-individual differences in pain in a sample of healthy adolescent and adult participants (N = 101).

Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain.

Introduction: Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline.

Amygdalar functional connectivity during resting and evoked pain in youth with functional abdominal pain disorders.

Pediatric functional abdominal pain disorders (FAPD) are highly prevalent, difficult to diagnose, and challenging to treat. The brain systems supporting FAPD remain poorly understood. This investigation examined the neuromechanisms of FAPD during a well-tolerated visceral pain induction task, the water load symptom provocation task (WL-SPT).

New insight into the neural mechanisms of migraine in adolescents: Relationships with sleep.

Objective: This case-control study examines if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents.

Background: Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Sleep is often disturbed in adolescents with migraine, and could contribute to the alterations in functional connectivity.

Processing of pain by the developing brain: evidence of differences between adolescent and adult females.

Adolescence is a sensitive period for both brain development and the emergence of chronic pain particularly in females. However, the brain mechanisms supporting pain perception during adolescence remain unclear. This study compares perceptual and brain responses to pain in female adolescents and adults to characterize pain processing in the developing brain.

Effect of percutaneous electrical nerve field stimulation on mechanosensitivity, sleep, and psychological comorbidities in adolescents with functional abdominal pain disorders.

Background: Percutaneous electrical nerve field stimulation (PENFS) improves symptoms in adolescents with functional abdominal pain disorders (FAPDs). However, little is known about its impact on sleep and psychological functioning. We evaluated the effects of PENFS on resting and evoked pain and nausea, sleep and psychological functioning, and long-term outcomes.

Brain Structural Changes During Juvenile Fibromyalgia: Relationships With Pain, Fatigue, and Functional Disability.

Objective: Juvenile fibromyalgia (FM) is a prevalent chronic pain condition affecting children and adolescents worldwide during a critical period of brain development. To date, no published studies have addressed the pathophysiology of juvenile FM. This study was undertaken to characterize gray matter volume (GMV) alterations in juvenile FM patients for the first time, and to investigate their functional and clinical relevance.

Pain sensitivity does not differ between obese and healthy weight individuals.

Introduction: There is emerging evidence suggesting a relationship between obesity and chronic pain.

Objectives: The aim of this study was to determine whether pain-free obese individuals display altered pain responses to acute noxious stimuli, thus raising the possibility of greater pain sensitivity and potential susceptibility for chronic pain development.

Methods: Psychophysical and anthropometric data were collected from 38 individuals with an obese body mass index (BMI) classification (BMI ≥ 30) and 41 age/sex-matched individuals of a healthy BMI (BMI < 24.

Does central nervous system dysfunction underlie patellofemoral pain in young females? Examining brain functional connectivity in association with patient-reported outcomes.

Patellofemoral pain (PFP) is defined as retro- or peri-patellar knee pain without a clear structural abnormality. Unfortunately, many current treatment approaches fail to provide long-term pain relief, potentially due to an incomplete understanding of pain-disrupted sensorimotor dysfunction within the central nervous system. The purposes of this study were to evaluate brain functional connectivity in participants with and without PFP, and to determine the relationship between altered brain functional connectivity in association with patient-reported outcomes.