An inhibitory circuit from central amygdala to zona incerta drives pain-related behaviors in mice.

Central amygdala neurons expressing protein kinase C-delta (CeA-PKCδ) are sensitized following nerve injury and promote pain-related responses in mice. The neural circuits underlying modulation of pain-related behaviors by CeA-PKCδ neurons, however, remain unknown. In this study, we identified a neural circuit that originates in CeA-PKCδ neurons and terminates in the ventral region of the zona incerta (ZI), a subthalamic structure previously linked to pain processing.

Human Stem Cell-Derived TRPV1-Positive Sensory Neurons: A New Tool to Study Mechanisms of Sensitization.

Somatosensation, the detection and transduction of external and internal stimuli such as temperature or mechanical force, is vital to sustaining our bodily integrity. But still, some of the mechanisms of distinct stimuli detection and transduction are not entirely understood, especially when noxious perception turns into chronic pain. Over the past decade major progress has increased our understanding in areas such as mechanotransduction or sensory neuron classification.

Disability Among Persons With Chronic Severe Back Pain: Results From a Nationally Representative Population-based Sample.

We evaluated the association between the chronic severe back pain with disability and participation, in U.S. Adults using data from the US 2019 National Health Interview Survey.

Sound induces analgesia through corticothalamic circuits.

Sound-including music and noise-can relieve pain in humans, but the underlying neural mechanisms remain unknown. We discovered that analgesic effects of sound depended on a low (5-decibel) signal-to-noise ratio (SNR) relative to ambient noise in mice. Viral tracing, microendoscopic calcium imaging, and multitetrode recordings in freely moving mice showed that low-SNR sounds inhibited glutamatergic inputs from the auditory cortex (ACx) to the thalamic posterior (PO) and ventral posterior (VP) nuclei.

Advancing Research on Medical Image Perception by Strengthening Multidisciplinary Collaboration.

Medical image interpretation is central to detecting, diagnosing, and staging cancer and many other disorders. At a time when medical imaging is being transformed by digital technologies and artificial intelligence, understanding the basic perceptual and cognitive processes underlying medical image interpretation is vital for increasing diagnosticians' accuracy and performance, improving patient outcomes, and reducing diagnostician burnout. Medical image perception remains substantially understudied.

PIEZO2 ion channels in proprioception.

PIEZO2 is a stretch-gated ion channel that is expressed at high levels in somatosensory neurons. Humans with rare mutations in the PIEZO2 gene have profound mechanosensory deficits that include a loss of the sense of proprioception. These striking phenotypes match those seen in conditional knockout mouse models demonstrating the highly conserved function for this gene.

Individual variability in brain representations of pain.

Characterizing cerebral contributions to individual variability in pain processing is crucial for personalized pain medicine, but has yet to be done. In the present study, we address this problem by identifying brain regions with high versus low interindividual variability in their relationship with pain. We trained idiographic pain-predictive models with 13 single-trial functional MRI datasets (n = 404, discovery set) and quantified voxel-level importance for individualized pain prediction.

The trial to assess chelation therapy 2 (TACT2): Rationale and design.

Background: Intravenous edetate disodium-based infusions reduced cardiovascular events in a prior clinical trial. The Trial to Assess Chelation Therapy 2 (TACT2) will replicate the initial study design.

Methods: TACT2 is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly infusions of a multi-component edetate disodium (disodium ethylenediamine tetra-acetic acid, or NaEDTA)-based chelation solution and twice daily oral, high-dose multivitamin and mineral supplements in patients with diabetes and a prior myocardial infarction (MI).

Sex differences in pain-related behaviors and clinical progression of disease in mouse models of colonic pain.

Previous studies have reported sex differences in patients with irritable bowel syndrome and inflammatory bowel disease, including differences in visceral pain perception. Despite this, sex differences in behavioral manifestations of visceral pain and underlying pathology of the gastrointestinal tract have been largely understudied in preclinical research. In this study, we evaluated potential sex differences in spontaneous nociceptive responses, referred abdominal hypersensitivity, disease progression, and bowel pathology in mouse models of acute and persistent colon inflammation.

Physician Office Visits That Included Complementary Health Approaches in U.S. Adults: 2005-2015.

The Institute of Medicine has described the need for comparing models of care delivery involving complementary health approaches and conventional medical practitioners. As a step toward addressing this need, we used a nationally representative 11-year sample of office-based visits to physicians from the National Ambulatory Medical Care Survey (NAMCS), to examine a comprehensive list of factors believed to be associated with visits where complementary health approaches were recommended or provided. NAMCS is a national health care survey designed to collect data on the provision and use of ambulatory medical care services provided by office-based physicians in the United States.

Reasons Office-Based Physicians in the United States Recommend Common Complementary Health Approaches to Patients: An Exploratory Study Using a National Survey.

To examine the reasons why office-based physicians do or do not recommend four selected complementary health approaches to their patients in the context of the Andersen Behavioral Model. Descriptive estimates of physician-level data from the 2012 National Ambulatory Medical Care Survey (NAMCS) Physician Induction Interview, a nationally representative survey of office-based physicians ( = 5622, weighted response rate = 59.7%).

A multistudy analysis reveals that evoked pain intensity representation is distributed across brain systems.

Information is coded in the brain at multiple anatomical scales: locally, distributed across regions and networks, and globally. For pain, the scale of representation has not been formally tested, and quantitative comparisons of pain representations across regions and networks are lacking. In this multistudy analysis of 376 participants across 11 studies, we compared multivariate predictive models to investigate the spatial scale and location of evoked heat pain intensity representation.

Functional Magnetic Resonance Imaging Studies in Sexual Medicine: A Primer.

Background: Over the past 30 years, functional magnetic resonance imaging (fMRI) has emerged as a powerful tool to non-invasively study the activity and function of the human brain. But along with the potential of fMRI to shed light on neurological, psychiatric, and psychological processes, there are methodological challenges and criticisms.

Aim: We herein provide an fMRI primer designed for a diverse audience, from the neuroimaging novice to the experienced user.

A Review of Potential National Chronic Pain Surveillance Systems in the United States.

Pain has been established as a major public health problem in the United States (U.S.) with 50 million adults experiencing chronic pain and 20 million afflicted with high-impact chronic pain (ie, chronic pain that interferes with life or work activities).

Making Connections to Improve Health Outcomes.

This issue of Global Advances in Health and Medicine sends a vital message about the importance of whole person health. Whole person health rests on the idea that our health involves multiple interconnected factors across physiological systems, as well as biological, behavioral, social, and environmental domains. The urgency of better understanding whole person health is highlighted by the current global health crisis.

Test-Retest Reliability of an Adaptive Thermal Pain Calibration Procedure in Healthy Volunteers.

Quantitative sensory testing (QST) allows researchers to evaluate associations between noxious stimuli and acute pain in clinical populations and healthy participants. Despite its widespread use, our understanding of QST's reliability is limited, as reliability studies have used small samples and restricted time windows. We examined the reliability of pain ratings in response to noxious thermal stimulation in 171 healthy volunteers (n = 99 female, n = 72 male) who completed QST on multiple visits ranging from 1 day to 952 days between visits.

NCCIH Priorities for Natural Products Research.

The National Center for Complementary and Integrative Health (NCCIH) is the lead agency within the U. S. federal government for complementary and integrative health research, which includes natural products.

Threat imminence reveals links among unfolding of anticipatory physiological response, cortical-subcortical intrinsic functional connectivity, and anxiety.

Excessive expression of fear responses in anticipation of threat occurs in anxiety, but understanding of underlying pathophysiological mechanisms is limited. Animal research indicates that threat-anticipatory defensive responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from basic neuroscience research in animals on threat imminence could guide mechanistic research in humans mapping abnormal function in this circuitry to aberrant defensive responses in pathological anxiety.

Effect sizes and test-retest reliability of the fMRI-based neurologic pain signature.

Identifying biomarkers that predict mental states with large effect sizes and high test-retest reliability is a growing priority for fMRI research. We examined a well-established multivariate brain measure that tracks pain induced by nociceptive input, the Neurologic Pain Signature (NPS). In N = 295 participants across eight studies, NPS responses showed a very large effect size in predicting within-person single-trial pain reports (d = 1.

Rating expectations can slow aversive reversal learning.

The process of learning allows organisms to develop predictions about outcomes in the environment, and learning is sensitive to both simple associations and higher order knowledge. However, it is unknown whether consciously attending to expectations shapes the learning process itself. Here, we directly tested whether rating expectations shapes arousal during classical conditioning.

Vagus nerve afferent stimulation: Projection into the brain, reflexive physiological, perceptual, and behavioral responses, and clinical relevance.

The afferent vagus nerves project to diverse neural networks within the brainstem and forebrain, based on neuroanatomical, neurophysiological, and functional (fMRI) brain imaging evidence. In response to afferent vagal stimulation, multiple homeostatic visceral reflexes are elicited. Physiological stimuli and both invasive and non-invasive electrical stimulation that activate the afferent vagus elicit perceptual and behavioral responses that are of physiological and clinical significance.