Vitaly Napadow

Spaulding Rehabilitation Hospital · Department of Physical Medicine and Rehabilitation

While patients suffering from fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. In this study we investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain such as anticipati...

The autonomic nervous system (ANS) is of paramount importance for daily life. Its regulatory action on respiratory, cardiovascular, digestive, endocrine, and many other systems is controlled by a number of structures in the CNS. While the majority of these nuclei and cortices have been identified in animal models, neuroimaging studies have recently...

Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure c...

Objective Transcutaneous auricular vagus nerve stimulation (tVNS) may be an innovative treatment for symptoms of knee osteoarthritis (OA) due to possible shared pathological mechanisms between diminished parasympathetic function, central pain mechanisms, and knee pain. Thus, we sought to test the safety and preliminary efficacy of tVNS in people wi...

Cyclic vomiting syndrome (CVS) is a disorder of brain-gut interaction characterized by recurrent episodes of nausea and vomiting interspersed with asymptomatic periods and associated with autonomic nervous system dysfunction. We examined the dysautonomic response to noxious stimuli seen in CVS patients using our previously validated approach to int...

Background Heart-Smile Training (HST) is an interoceptive compassion-based behavioral intervention that in case reports has been beneficial for depression. Interoception refers to the awareness and regulation of physiological signals from inside the body. Depressed patients often have diminished interoceptive awareness and often experience disconne...

Introduction Acupuncture therapy has achieved global expansion and shown promise for health promotion and treatment of acute/chronic pain. Objectives To present an update on the existing evidence base for research and clinical practice supporting acupuncture analgesia. Methods This Clinical Update elaborates on the 2023 International Association...

Transcutaneous auricular vagus nerve stimulation (taVNS) targets subcutaneous axons in the auricular branch of the vagus nerve at the outer ear. Its non‐invasive nature makes it a potential treatment for various disorders. taVNS induces neuromodulatory effects within the nucleus of the solitary tract (NTS), and due to its widespread connectivity, t...

Menstrual pain is associated with deficits in central pain processing, yet neuroimaging studies to date have all been limited by focusing on group comparisons of adult women with vs without menstrual pain. This study aimed to investigate the role of the triple network model (TNM) of brain networks in adolescent girls with varied menstrual pain seve...

Introduction: The concept of acupoints is a key defining feature of acupuncture, yet the scientific basis of acupoints remains unclear. In recent years, there has been an emerging body of animal studies demonstrating an association between cutaneous sensitivity and visceral pathophysiology, through which acupoints over the skin are sensitized in pa...

Although inflammation is known to play a role in knee osteoarthritis (KOA), inflammation-specific imaging is not routinely performed. In this article, we evaluate the role of joint inflammation, measured using [ ¹¹ C]-PBR28, a radioligand for the inflammatory marker 18-kDa translocator protein (TSPO), in KOA. Twenty-one KOA patients and 11 healthy...

Objective Fibromyalgia (FM) is characterized by pervasive pain‐related symptomatology and high levels of negative affect. Mind–body treatments such as cognitive behavioral therapy (CBT) appear to foster improvement in FM via reductions in pain‐related catastrophizing, a set of negative, pain‐amplifying cognitive and emotional processes. However, th...

Background The autonomic response to transcutaneous auricular vagus nerve stimulation (taVNS) has been linked to the engagement of brainstem circuitry modulating autonomic outflow. However, the physiological mechanisms supporting such efferent vagal responses are not well understood, particularly in humans. Hypothesis We present a paradigm for est...

Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as “dosage” has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy partic...

Fibromyalgia has been characterized by augmented cross-network functional communication between the brain's sensorimotor, default mode, and attentional (salience/ventral and dorsal) networks. However, the underlying mechanisms of these aberrant communication patterns are unknown. In this study, we sought to understand large-scale topographic patter...

Recently, we showed that patients with knee osteoarthritis (KOA) demonstrate alterations in the thalamic concentrations of several metabolites compared with healthy controls: higher myo-inositol (mIns), lower N-acetylaspartate (NAA), and lower choline (Cho). Here, we evaluated whether these metabolite alterations are specific to KOA or could also b...

Social interactions such as the patient-clinician encounter can influence pain, but the underlying dynamic interbrain processes are unclear. Here, we investigated the dynamic brain processes supporting social modulation of pain by assessing simultaneous brain activity (fMRI hyperscanning) from chronic pain patients and clinicians during video-based...

It is assumed that mood can be inferred from one’s facial expression. While this association may prove to be an objective marker for mood disorders, few studies have explicitly evaluated this linkage.The facial movement responses of women with major depressive disorder (n = 66) and healthy controls (n = 46) under emotional stimuli were recorded usi...

Introduction: Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a potential treatment target. However, it is currently unknown whether modulating neuroinflammation effectively alleviates pain in humans. This trial tests the hypo...

Background The objective of this pilot study was to identify frequency-dependent effects of respiratory-gated auricular vagus afferent nerve stimulation (RAVANS) on the regulation of blood pressure and heart rate variability in hypertensive subjects and examine potential differential effects by sex/gender or race. Methods Twenty hypertensive subje...

Resting-state functional MRI (rs-fMRI) is being used to develop diagnostic, prognostic, and therapeutic biomarkers for critically ill patients with severe brain injuries. In studies of healthy volunteers and non-critically ill patients, prospective cardiorespiratory data are routinely collected to remove non-neuronal fluctuations in the rs-fMRI sig...

Interoceptive dysfunction is often present in anxiety and depression. We investigated the effects of an 8-week intervention, Mindfulness Training for Primary Care (MTPC), on brain mechanisms of interoceptive attention among patients with anxiety and/or depression. We hypothesized that fMRI brain response to interoception in the insula, a region kno...

Introduction: Chronic pain is a debilitating medical problem that is difficult to treat. Neuroinflammatory pathways have emerged as a potential therapeutic target, as preclinical studies have demonstrated that glial cells and neuroglial interactions play a role in the establishment and maintenance of pain. Recently, we used positron emission tomog...

The locus coeruleus (LC) is one of the most commonly studied brainstem nuclei when investigating brain–behavior associations. The LC serves as a major brainstem relay for both ascending bottom-up and descending top-down projections. Specifically, noradrenergic (NA) LC neurons not only connect globally to higher-order subcortical nuclei and cortex t...

Objective The COVID-19 pandemic has strongly influenced psychological and physical health worldwide. The aim of this study was to examine the impact of the pandemic on women with fibromyalgia. Methods This mixed methods pilot study explored measures of pain severity and interference, as well as pain catastrophizing and level of fibromyalgia impact...

Introduction Chronic pain is an extremely prevalent public health issue. However, the underlying mechanisms are poorly understood, thus limiting effective treatment options. Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a pot...

Objectives Various active control interventions for Mindfulness-Based Stress Reduction (MBSR) have been developed, though many can fall short in controlling for non-specific or placebo effects. We developed a Nature-Based Stress Reduction (NBSR) program based on previously reported positive results from virtual natural environment exposure on menta...

Background Functional dyspepsia (FD) is a disorder of gut–brain interaction, and its putative pathophysiology involves dysregulation of gastric motility and central processing of gastric afference. The vagus nerve modulates gastric peristalsis and carries afferent sensory information to brainstem nuclei, specifically the nucleus tractus solitarii (...

A previous study by our group showed that knee osteoarthritis (KOA) patients demonstrate alterations in the thalamic levels of several metabolites, as measured by 1H-magnetic resonance spectroscopy: i.e., higher myo-inositol (mIns), lower N-acetylaspartate (NAA) and lower Choline (Cho), when compared to healthy controls. We sought to replicate thes...

The patient/clinician relationship is central in clinical therapies for chronic pain and has been linked with treatment efficacy. To assess the brain mechanisms underlying these psychosocial interactions, neurophysiological objective measures are still needed. A recent publication from our team applied functional MRI hyperscanning (synchronized neu...

While the neural correlates of migraine have been widely studied, it remains unclear whether glial cells contribute to neuroinflammation in migraine. One marker of glial activation is the presence of elevated levels of 18 kDa translocator protein (TSPO), and earlier studies have shown that individuals suffering from migraine with aura (MWA) exhibit...

The patient-clinician therapeutic alliance is a powerful modulator shaping patients’ treatment experience and clinical outcomes. Before and after a 3-week electro-acupuncture intervention (6 sessions), fMRI hyper-scanning was applied to investigate the influence of either an Augmented (warm/attentive) or a Limited (neutral/business-like) clinician...

Migraine is a highly prevalent chronic pain disorder that is characterized by sensitization and dysregulation of the central autonomic nervous system. Interoception is the sensing of signals originating from within the body, and is altered in chronic pain conditions including episodic migraine. The relationship between brain mechanisms of interocep...

Objective To evaluate changes in cortical thickness and right posterior insula (r-pIns) gamma-aminobutyric acid (GABA) concentrations in veterans with fibromyalgia treated with auricular percutaneous electric nerve field stimulation (PENFS). Materials & Methods This was a randomized, controlled, open label investigation conducted in a government h...

Introduction: Despite substantial progress made in the field of acupuncture research, the existence and specificity of acupoints remain controversial. In recent years, the concept of acupoint sensitization has emerged as a theoretical framework for understanding acupoints as dynamic functional entities that are sensitized in pathological conditions...

Background The establishment of test–retest reliability and reproducibility (TRR) is an important part of validating any research tool, including functional magnetic resonance imaging (fMRI). The primary objective of this study is to investigate the reliability of pseudo-Continuous Arterial Spin Labeling (pCASL) and Blood Oxygen Level Dependent (BO...

Objective Abnormal central pain processing is a leading cause of pain in fibromyalgia (FM) and is perceptually characterized with the psychophysical measure of temporal summation of pain (TSP). TSP is the perception of increasingly greater pain in response to repetitive or tonic noxious stimuli. Previous neuroimaging studies have used static (i.e.,...

Objective Respiratory-gated Auricular Vagal Afferent Nerve stimulation (RAVANS) is a safe nonpharmacological approach to managing chronic pain. The purpose of the current study was to examine (1) the feasibility and acceptability of RAVANS, combined with mindful meditation (MM) for chronic low back pain (CLBP), (2) the potential synergy of MM+RAVAN...

Patient–clinician concordance in behavior and brain activity has been proposed as a potential key mediator of mutual empathy and clinical rapport in the therapeutic encounter. However, the specific elements of patient–clinician communication that may support brain-to-brain concordance and therapeutic alliance are unknown. Here, we investigated how...

This chapter introduces the neurocircuitry that mediates nausea and vomiting. It starts by explaining the concept of the dynamic threshold in triggering nausea. Subsequently, the anatomical pathways and interplay of central and peripheral autonomic pathways involved in the development of nausea and vomiting are delineated. Lastly, the proposed mech...

This column continues the JACM commentary series from the Society for Acupuncture Research (SAR). This is a first in the 5 years of this column partnership, a review of top developments in acupuncture research, with an eye to the way cultural contexts are compelling heightened or new foci for the field. The present commentary began with a survey pr...

Resting-state functional MRI (rs-fMRI) is being used to develop diagnostic, prognostic, and therapeutic biomarkers for critically ill patients with severe brain injuries. In studies of healthy volunteers and non-critically ill patients, prospective cardiorespiratory data are routinely collected to remove non-neuronal fluctuations in the rs-fMRI sig...

Carpal Tunnel Syndrome (CTS) is a median nerve entrapment neuropathy that alters primary somatosensory cortex (S1) organization. While electro-acupuncture (EA), a form of peripheral neuromodulation, has been shown to improve clinical and neurophysiological CTS outcomes, the role of EA-evoked brain response during therapy (within and beyond S1) for...

Objective Chronic pain can have detrimental effects on quality of life and a profound impact on one’s identity. The Pictorial Representation of Illness- and Self-Measure (PRISM), is a visual tool designed to measure the self-illness separation (SIS) that represents the degree of schema-enmeshment (i.e., the degree to which the self-schema and the i...

Background: The establishment of test-retest reliability and reproducibility (TRR) is an important part of validating any research tool, including functional magnetic resonance imaging (fMRI). The primary objective of this study is to investigate the reliability of pseudo-Continuous Arterial Spin Labeling (pCASL) and Blood Oxygen Level Dependent (B...

We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine, and Gulf War Illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18 kDa translocator protein, which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple...

Background Negative stress significantly impacts major depressive disorder (MDD), given the shared brain circuitry between the stress response and mood. Thus, interventions that target this circuitry will have an important impact on MDD. The aim of this study was to evaluate the acute effects of a novel respiratory-gated auricular vagal afferent ne...

The cover image is based on the Original Article Non‐uniform gastric wall kinematics revealed by 4D Cine magnetic resonance imaging in humans by Roberta Sclocco et al., https://doi.org/10.1111/nmo.14146.

The positron emission tomography (PET) radiotracer [ ¹¹ C]PBR28 has been increasingly used to image the translocator protein (TSPO) as a marker of neuroinflammation in a variety of brain disorders. Interrelatedly, similar clinical populations can also exhibit altered brain perfusion, as has been shown using arterial spin labelling in magnetic reson...

Background Fibromyalgia is a centralized multidimensional chronic pain syndrome, but its pathophysiology is not fully understood. Methods We applied 3D magnetic resonance spectroscopic imaging (MRSI), covering multiple cortical and subcortical brain regions, to investigate the association between neuro-metabolite (e.g., combined glutamate and glut...