Subcutaneous Oxytocin Injection Reduces Heat Pain: A Randomized-Controlled Trial.

Oxytocin (OT) is a neuropeptide broadly implicated in social relationships and behavior. OT also exerts antinociceptive and pain-reducing effects in both humans and rodents. Recent research in rodents demonstrates that these effects can be peripheral and local.

Pain mechanisms in the transgender individual: a review.

Specific Aim: Provide an overview of the literature addressing major areas pertinent to pain in transgender persons and to identify areas of primary relevance for future research.

Methods: A team of scholars that have previously published on different areas of related research met periodically though zoom conferencing between April 2021 and February 2023 to discuss relevant literature with the goal of providing an overview on the incidence, phenotype, and mechanisms of pain in transgender patients. Review sections were written after gathering information from systematic literature searches of published or publicly available electronic literature to be compiled for publication as part of a topical series on gender and pain in the Frontiers in Pain Research.

Real-world outcomes from a series of patients with late onset Pompe disease who switched from alglucosidase alfa to avalglucosidase alfa.

Pompe disease is an inherited, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase and accumulation of glycogen in tissues, resulting in cellular dysfunction, muscle damage, and functional disabilities. Enzyme replacement therapy with alglucosidase alfa (Myozyme/Lumizyme) has led to better outcomes, but many patients have plateaued or declined despite treatment. The second-generation ERT avalglucosidase alfa (Nexviazyme) was designed to have enhanced cellular uptake via the conjugation of additional bis-mannose-6-phosphate residues.

Screening data from 19 patients with late-onset Pompe disease for a phase I clinical trial of AAV8 vector-mediated gene therapy.

Late-onset Pompe disease (LOPD) is a multisystem disorder with significant myopathy. The standard treatment is enzyme replacement therapy (ERT), a therapy that is lifesaving, yet with limitations. Clinical trials have emerged for other potential treatment options, including adeno-associated virus (AAV) gene therapy.

Muscle ultrasound in patients with late-onset Pompe disease identified by newborn screening.

Importance: Implementation of newborn screening (NBS) in the United States now detects infants with late-onset Pompe disease (LOPD), a lysosomal storage disease characterized by slowly progressive muscle weakness, and detailed clinical evaluation has identified early muscle weakness. Biomarkers may be uninformative; thus, non-invasive imaging is needed to assess early LOPD muscle changes. Muscle ultrasound (US) measuring echointensity (EI) is a non-invasive measure of muscle health.

Aβ-CT Affective Touch: Touch Pleasantness Ratings for Gentle Stroking and Deep Pressure Exhibit Dependence on A-Fibers.

Gentle stroking of the skin is a common social touch behavior with positive affective consequences. A preference for slow versus fast stroking of hairy skin has been closely linked to the firing of unmyelinated C-tactile (CT) somatosensory afferents. Because the firing of CT afferents strongly correlates with touch pleasantness, the CT pathway has been considered a social-affective sensory pathway.

Chronic pain patients low in social connectedness report higher pain and need deeper pressure for pain relief.

The experience of rejection and disconnection reliably amplifies pain. Yet, little is known about the impact of enduring feelings of closeness, or social connectedness, on experiences of chronic pain. The current secondary analysis tested the hypothesis that greater social connectedness would predict lower chronic pain ratings, mediated by lower depression and anxiety.

Phase I study of liver depot gene therapy in late-onset Pompe disease.

Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for enzyme replacement therapy (ERT) by creating a liver depot for acid α-glucosidase (GAA) production. We report initial safety and bioactivity of the first dose (1.6 × 10 vector genomes/kg) cohort (n = 3) in a 52-week open-label, single-dose, dose-escalation study (NCT03533673) in patients with late-onset Pompe disease (LOPD).

Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource.

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity. Consequently, glycogen synthesis is impaired and leads to accumulation of poorly branched glycogen known as polyglucosan. GSD IV is characterized by a remarkable degree of phenotypic heterogeneity with presentations in utero, during infancy, early childhood, adolescence, or middle to late adulthood.

Motor function and safety after allogeneic cord blood and cord tissue-derived mesenchymal stromal cells in cerebral palsy: An open-label, randomized trial.

Aim: To evaluate safety and motor function after treatment with allogeneic umbilical cord blood (AlloCB) or umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy (CP).

Method: Ninety-one children (52 males, 39 females; median age 3 years 7 months [range 2-5 years]) with CP due to hypoxic-ischemic encephalopathy, stroke, or periventricular leukomalacia were randomized to three arms: (1) the AlloCB group received 10 × 10 AlloCB total nucleated cells (TNC) per kilogram at baseline (n = 31); (2) the hCT-MSC group received 2 × 10 hCT-MSC at baseline, 3 months, and 6 months (n = 28); (3) the natural history control group received 10 × 10 AlloCB TNC per kilogram at 12 months (n = 31). Motor function was assessed with the Gross Motor Function Measure-66 (GMFM-66) and Peabody Developmental Motor Scale, Second Edition.

Early clinical phenotype of late onset Pompe disease: Lessons learned from newborn screening.

Purpose: Thoroughly phenotype children with late-onset Pompe disease (LOPD) diagnosed via newborn screening (NBS) to provide guidance for long-term follow up.

Methods: Twenty infants ages 6-21 months with LOPD diagnosed by NBS underwent systematic clinical evaluation at Duke University including cardiac imaging, biomarker testing, physical therapy evaluation, and speech-language pathology evaluation.

Results: Of the 20 infants, four were homozygous for the "late-onset" IVS1 splice site variant c.

A retrospective longitudinal study and comprehensive review of adult patients with glycogen storage disease type III.

Introduction: A deficiency of glycogen debrancher enzyme in patients with glycogen storage disease type III (GSD III) manifests with hepatic, cardiac, and muscle involvement in the most common subtype (type a), or with only hepatic involvement in patients with GSD IIIb.

Objective And Methods: To describe longitudinal biochemical, radiological, muscle strength and ambulation, liver histopathological findings, and clinical outcomes in adults (≥18 years) with glycogen storage disease type III, by a retrospective review of medical records.

Results: Twenty-one adults with GSD IIIa (14 F & 7 M) and four with GSD IIIb (1 F & 3 M) were included in this natural history study.

Physical therapy assessment and whole-body magnetic resonance imaging findings in children with glycogen storage disease type IIIa: A clinical study and review of the literature.

Introduction: Early recognized manifestations of GSD III include hypoglycemia, hepatomegaly, and elevated liver enzymes. Motor symptoms such as fatigue, muscle weakness, functional impairments, and muscle wasting are typically reported in the 3rd to 4th decade of life.

Objective: In this study, we investigated the early musculoskeletal findings in children with GSD IIIa, compared to a cohort of adults with GSD IIIa.

Widespread Pressure Delivered by a Weighted Blanket Reduces Chronic Pain: A Randomized Controlled Trial.

Pleasant sensation is an underexplored avenue for modulation of chronic pain. Deeper pressure is perceived as pleasant and calming, and can improve sleep. Although pressure can reduce acute pain, its effect on chronic pain is poorly characterized.

Sibling umbilical cord blood infusion is safe in young children with cerebral palsy.

Preclinical and early phase clinical studies suggest that an appropriately dosed umbilical cord blood (CB) infusion has the potential to help improve motor function in young children with cerebral palsy (CP). As many children with CP do not have their own CB available, use of allogeneic cells would extend access to this potentially beneficial therapy to more children. In this phase I, open-label study, 15 children, aged 1 to 6 years, with moderate to severe spastic CP were treated with a single intravenous infusion of allogeneic human leukocyte antigen (HLA) matched or partially matched sibling CB with a cell dose of ≥2.

Innocuous pressure sensation requires A-type afferents but not functional ΡΙΕΖΟ2 channels in humans.

The sensation of pressure allows us to feel sustained compression and body strain. While our understanding of cutaneous touch has grown significantly in recent years, how deep tissue sensations are detected remains less clear. Here, we use quantitative sensory evaluations of patients with rare sensory disorders, as well as nerve blocks in typical individuals, to probe the neural and genetic mechanisms for detecting non-painful pressure.

The Role of Expectations and Endogenous Opioids in Mindfulness-Based Relief of Experimentally Induced Acute Pain.

Objective: Expectations contribute to cognitive pain modulation through opioidergically mediated descending inhibition. Mindfulness meditation reduces pain independent of endogenous opioids, engaging unique corticothalamocortical mechanisms. However, it remains unknown whether expectations for pain relief predict mindfulness-induced analgesia and if these expectations are modified by endogenous opioids.

Quantitative whole-body magnetic resonance imaging in children with Pompe disease: Clinical tools to evaluate severity of muscle disease.

Objective: Since the introduction of enzyme replacement therapy (ERT) with alglucosidase alfa, there has been increased survival in patients with Pompe disease. It is essential to characterize and quantify the burden of disease in these patients. Here, we report a measure of muscle fat infiltration in children with infantile and pediatric late-onset Pompe disease (IPD and LOPD, respectively) to better understand the extent of muscle involvement.

Respiratory muscle training in late-onset Pompe disease: Results of a sham-controlled clinical trial.

To address progressive respiratory muscle weakness in late-onset Pompe disease (LOPD), we developed a 12-week respiratory muscle training (RMT) program. In this exploratory, double-blind, randomized control trial, 22 adults with LOPD were randomized to RMT or sham-RMT. The primary outcome was maximum inspiratory pressure (MIP).

Neurophysiological Mechanisms Supporting Mindfulness Meditation-Based Pain Relief: an Updated Review.

Purpose Of Review: This review examines recent (2016 onwards) neuroscientific findings on the mechanisms supporting mindfulness-associated pain relief. To date, its clear that mindfulness lowers pain by engaging brain processes that are distinct from placebo and vary across meditative training level. Due to rapid developments in the field of contemplative neuroscience, an update review on the neuroimaging studies focused on mindfulness, and pain is merited.

Pleasant Deep Pressure: Expanding the Social Touch Hypothesis.

Neuroscientific research on pleasant touch has focused on the C-tactile pathway for gentle stroking and has successfully explained how these sensory fibers transmit information about affective social touch to the brain and induce sensations of pleasantness. The C-tactile social/affective touch hypothesis even proposes that C-tactile fibers form a privileged pathway underlying social touch. However, deep pressure is a type of touch commonly considered pleasant and calming, occurring in hugs, cuddling, and massage.

Training, detraining, and retraining: Two 12-week respiratory muscle training regimens in a child with infantile-onset Pompe disease.

Background: Respiratory muscle weakness is a primary cause of morbidity and mortality in patients with Pompe disease. We previously described the effects of our 12-week respiratory muscle training (RMT) regimen in 8 adults with late-onset Pompe disease [1] and 2 children with infantile-onset Pompe disease [2].

Case Report: Here we describe repeat enrollment by one of the pediatric participants who completed a second 12-week RMT regimen after 7 months of detraining.

Higher dosing of alglucosidase alfa improves outcomes in children with Pompe disease: a clinical study and review of the literature.

Purpose: Enzyme replacement therapy (ERT) with recombinant human acid-α glucosidase (rhGAA) at standard dose of 20 mg/kg every other week is insufficient to halt the long-term progression of myopathy in Pompe disease.

Methods: We conducted a retrospective study on infantile-onset Pompe disease (IPD) and late-onset Pompe disease (LOPD) patients with onset before age 5 years, ≥12 months of treatment with standard dose ERT, and rhGAA immunogenic tolerance prior to dose escalation. Long-term follow-up of up to 18 years was obtained.

Improved muscle function in a phase I/II clinical trial of albuterol in Pompe disease.

This 24-week, Phase I/II, double-blind, randomized, placebo-controlled study investigated the safety and efficacy of extended-release albuterol in late-onset Pompe disease stably treated with enzyme replacement therapy at the standard dose for 4.9 (1.0-9.