Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required.
View Article and Find Full Text PDFThis article presents an overview of the pain research programs within the National Institutes of Health (NIH) Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®. Launched in 2018 to address the opioid crisis, the NIH HEAL Initiative supports research on addiction prevention and treatment. A key component of addiction prevention is the development of new, effective, non-addictive treatments for acute and chronic pain.
View Article and Find Full Text PDFEClinicalMedicine
December 2023
Background: Pain is the leading cause of disability worldwide among adults and effective treatment options remain elusive. Data harmonization efforts, such as through core outcome sets (COS), could improve care by highlighting cross-cutting pain mechanisms and treatments. Existing pain-related COS often focus on specific conditions, which can hamper data harmonization across various pain states.
View Article and Find Full Text PDFBackground: Vacuolar protein sorting 13 homolog A (VPS13A) disease, historically known as chorea-acanthocytosis, is a rare neurodegenerative disorder caused by biallelic mutations in VPS13A, usually resulting in reduced or absent levels of its protein product, VPS13A. VPS13A localizes to contact sites between subcellular organelles, consistent with its recently identified role in lipid transfer between membranes. Mutations are associated with neuronal loss in the striatum, most prominently in the caudate nucleus, and associated marked astrogliosis.
View Article and Find Full Text PDFBackground: Chorea-acanthocytosis (ChAc) is associated with mutations of VPS13A, which encodes for chorein, a protein implicated in lipid transport at intracellular membrane contact sites.
Objectives: The goal of this study was to establish the lipidomic profile of patients with ChAc.
Methods: We analyzed 593 lipid species in the caudate nucleus (CN), putamen, and dorsolateral prefrontal cortex (DLPFC) from postmortem tissues of four patients with ChAc and six patients without ChAc.
Chronic pain conditions like genito-pelvic pain penetration disorder and chronic pelvic pain cause significant morbidity in women worldwide and yet are underdiagnosed and undertreated. While the use of botulinum toxin for pain conditions has expanded, there are few randomized controlled studies of botulinum toxin for pelvic pain conditions in women. This paper provides an update on the current status and context for considering botulinum toxin treatment for these conditions to complement and expand currently available approaches.
View Article and Find Full Text PDFMany questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care.
View Article and Find Full Text PDFEndometriosis is a heterogeneous disease where neurogenic sensitization can lead to chronic pain within and beyond the pelvis. Coincident pain and comorbidities merit specific attention. We discuss the causes, comorbidities, and management of endometriosis-associated chronic pelvic pain, advocating for a multidisciplinary approach to develop more effective treatments.
View Article and Find Full Text PDFBackground: Botulinum neurotoxin (BoNT) injection is an established therapy for limb spasticity and focal limb dystonia. Comparative benefits of injection guidance procedures have not been rigorously studied.
Objectives: We compared 2 targeting techniques for onabotulinumtoxin-A (onabotA) injection for the treatment of focal hand dystonia and upper limb spasticity: electrophysiologic guidance using electrical stimulation (E-stim) and ultrasound (US).
Neurotherapeutics
September 2022
Drug development abounds with corporate pharmaceutical capital investment and expenditure costs for new therapeutics. However, there is little data on the human investment, in particular, the number of participants required or the potential burden on and cost to individual trial participants so instrumental to this endeavor. Indeed, the human participant burden in clinical trials is poorly, if at all, described in the literature and we could identify no reports that have detailed the participant burden unique to neurology trials.
View Article and Find Full Text PDFClinical studies conducted by the National Institutes of Health's Intramural Research Program (NIH-IRP) provide eligible individuals with access to innovative research treatments that may not otherwise be available. The NIH-IRP's mission is to include all Americans, including American Indians and Alaska Natives, in its clinical research. This study is the first to provide data about inclusion of American Indians/Alaska Natives in NIH-IRP clinical studies.
View Article and Find Full Text PDFBackground: Chronic pelvic pain persists in some women with endometriosis even after lesion removal and optimized hormonal treatment.
Objective: Characterize the presence and distribution of pain, myofascial dysfunction and sensitisation beyond the pelvis in women with endometriosis-associated chronic pelvic pain.
Methods: Cross-sectional study of 30 women prior to participation in a clinical trial.
Chemodenervation of cervical musculature using botulinum neurotoxin (BoNT) is established as the gold standard or treatment of choice for management of Cervical Dystonia (CD). The success of BoNT procedures is measured by improved symptomology while minimizing side effects and is dependent upon many factors including: clinical pattern recognition, identifying contributory muscles, BoNT dosage, and locating and safely injecting target muscles. In patients with CD, treatment of anterocollis (forward flexion of the neck) and anterocaput (anterocapitis) (forward flexion of the head) are inarguably challenging.
View Article and Find Full Text PDFParkinsonism Relat Disord
November 2020
With this retrospective, single center, chart review study, we investigate the self-reported benefit and weakness after botulinum toxin injections in three different types of dystonia: focal hand dystonia (FHD), blepharospasm and cervical dystonia. We found that the benefit lasts significantly longer in FHD compared to the other two groups.
View Article and Find Full Text PDFOpioid-related death and overdose have now reached epidemic proportions. In response to this public health crisis, the National Institutes of Health (NIH) launched the Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. Herein, we describe two NIH HEAL Initiative programs to accelerate development of non-opioid, non-addictive pain treatments: The Preclinical Screening Platform for Pain (PSPP) and Early Phase Pain Investigation Clinical Network (EPPIC-Net).
View Article and Find Full Text PDFBackground: Writer's cramp (WC) is a form of focal hand dystonia, for which focal botulinum neurotoxin (BoNT) injections are the current best therapy. Past studies have shown that some types of rehabilitative therapy can be useful. We hypothesized that BoNT together with a specific type of occupational therapy would be better than BoNT alone for treating WC patients comparing the effects with a patient-rated subjective scale.
View Article and Find Full Text PDFBackground And Objectives: Many women with endometriosis continue to have pelvic pain despite optimal surgical and hormonal treatment; some also have palpable pelvic floor muscle spasm. We describe changes in pain, spasm, and disability after pelvic muscle onabotulinumtoxinA injection in women with endometriosis-associated pelvic pain, a specific population not addressed in prior pelvic pain studies on botulinum toxin.
Methods: We present an open-label proof-of-concept case series of women with surgically diagnosed endometriosis.
Introduction And Hypothesis: Botulinum toxin (BoNT) is increasingly used for pain, especially with muscle spasm. We describe our methodology for BoNT treatment of chronic pelvic pain (CPP) in women and place it in the context of the literature on techniques for this use.
Methods: Databases were searched using terms "botulinum toxin," "pelvic pain," and "vaginismus.
We thank the authors for their detailed letter and salient comments related to our article on Ultrasound Guidance for botulinum toxin (BoNT) injections.[..
View Article and Find Full Text PDFLocation data are becoming easier to obtain and are now bundled with other metadata in a variety of biomedical research applications. At the same time, the level of sophistication required to protect patient privacy is also increasing. In this article, we provide guidance for institutional review boards (IRBs) to make informed decisions about privacy protections in protocols involving location data.
View Article and Find Full Text PDFRunner’s dystonia (RD) is a task-specific focal dystonia of the lower limbs that occurs when running. In this retrospective case series, we present surface electromyography (EMG) and joint kinematic data from thirteen patients with RD who underwent instrumented gait analysis (IGA) at the Functional and Biomechanics Laboratory at the National Institutes of Health. Four cases of RD are described in greater detail to demonstrate the potential utility of EMG with kinematic studies to identify dystonic muscle groups in RD.
View Article and Find Full Text PDFSelection of muscles for botulinum toxin injection for limb dystonia is particularly challenging. Limb dystonias vary more widely in the pattern of dystonic movement and involved muscles than cervical dystonia or blepharospasm. The large variation in how healthy individuals perform skilled hand movements, the large number of muscles in the hand and forearm, and the presence of compensatory actions in patients with dystonia add to the complexity of choosing muscles for injection.
View Article and Find Full Text PDFToxins (Basel)
December 2017
Injections of botulinum neurotoxins (BoNTs) are prescribed by clinicians for a variety of disorders that cause over-activity of muscles; glands; pain and other structures. Accurately targeting the structure for injection is one of the principle goals when performing BoNTs procedures. Traditionally; injections have been guided by anatomic landmarks; palpation; range of motion; electromyography or electrical stimulation.
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