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...

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...

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...

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...

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...

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...

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...

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 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...

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

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...

In chronic pain management and treatment, a positive patient-clinician relationship is associated with higher patient satisfaction and treatment efficacy. In this study, we investigated synchronization of brain activity between patients and clinicians during an experimentally controlled augmented (empathetic) compared to limited (business-like) cli...

The weak association between disability levels and “peripheral” (i.e., knee) findings suggests that central nervous system alterations may contribute to the pathophysiology of knee osteoarthritis (KOA). Here, we evaluated brain metabolite alterations in KOA patients, before and after total knee arthroplasty (TKA), using 1H-magnetic resonance spectr...

Carpal Tunnel Syndrome (CTS) is an entrapment neuropathy of the median nerve that alters the organization of the brain's primary somatosensory cortex (S1), both structurally and functionally. Our prior research also demonstrated that electro-acupuncture (EA), both local and remote/distal to the wrist, but not sham acupuncture, improved S1 somatotop...

We recently showed elevated levels of the 18kDa translocator protein (TSPO), a marker of neuroinflammation, in chronic low back pain patients (cLBP) compared to healthy controls(Loggia et al., 2015). Here, we test whether TSPO signal 1) can further subtype cLBP patients based on their clinical presentation, and 2) is associated with functional conn...

Compared to healthy controls (HC), fibromyalgia (FM) patients exhibit enhanced temporal summation of pain (TSP) – i.e. perception of increasingly greater pain in response to repetitive or sustained noxious stimuli. Previous neuroimaging studies have linked static functional connectivity (sFC) and stimulus-evoked brain fMRI response to enhanced TSP...

Functional dyspepsia (FD) is a common gastrointestinal (GI) disorder of the upper GI tract associated with a variety of symptoms, such as abdominal pain and bloating, but lacking identifiable organic abnormalities. Altered motility patterns in FD occur in the stomach, pylorus and small intestine during digestive or interdigestive periods, and up to...

While patient/clinician relationships significantly impact pain outcomes, the behavioral and neural mechanisms supporting this phenomenon are unknown. Specifically, the precise role of facial expressions in contributing to analgesia and brain-to-brain communication has not been investigated. In this Hyperscan fMRI study, we explored how pain-relate...

Research suggests that a good patient-clinician therapeutic alliance can improve clinical outcomes. In this ongoing, longitudinal study, we applied fMRI hyper-scanning to determine whether behavioral, neural, and clinical variables associated with the therapeutic relationship between chronic pain patients and their clinicians influences clinical ou...

Chronic pain is characterized by hyperalgesia and heightened temporal summation of pain, however, the brain mechanisms underlying these phenomena remain understudied. We sought to understand the relationship of hyperalgesia and temporal summation with the balance between basal excitatory and inhibitory neurotransmission (E-I balance) and brain func...

Chronic low back pain (CLBP) is the leading cause of disability in the United States. There is considerable interest in the development of safe, effective, nonpharmacological approaches to managing CLBP. Respiratory-gated electrical stimulation of the somatosensory vagal afferent receptors in the ear (RAVANS), has been shown to reduce chronic pelvi...

Fibromyalgia is a multidimensional chronic pain syndrome. It is thought to result mainly from central nervous system dysfunction, but its working mechanism is not fully understood. In this study, we applied multi-slice magnetic resonance spectroscopy imaging (MRSI) to investigate the relationship between brain metabolite (e.g., combined glutamate a...

Previous studies have demonstrated that fibromyalgia results in gray matter alterations as well as changes in GABA concentrations in various cortical regions when compared to healthy controls [1,2,3]. In veterans with fibromyalgia, we investigate the effect of PENFS on gray matter alterations and GABA concentrations and correlate them with clinical...

Background Assessment of gastric function in humans has relied on modalities with varying degrees of invasiveness, which are usually limited to the evaluation of single aspects of gastric function, thus requiring patients to undergo a number of often invasive tests for a full clinical understanding. Therefore, the development of a non‐invasive tool...

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in...

'Blinding' involves concealing knowledge of which trial participants received the interventions from participants themselves and other trial personnel throughout the trial. Blinding reduces bias arising from the beliefs and expectations of these groups. It is agreed that where possible, blinding should be attempted, for example by ensuring that exp...

Objective: To examine the role of several interrelated, potentially modifiable psychological factors (i.e., mindfulness and catastrophizing) in influencing patient-reported functioning. Methods: In this cross-sectional study, 107 patients with fibromyalgia completed self-report assessments of pain severity, functioning and impact of symptoms, mi...

The weak association between disability levels and "peripheral" (i.e., knee) findings suggests that central nervous system alterations may contribute to the pathophysiology of knee osteoarthritis (KOA). Here, we evaluated brain metabolite alterations in KOA patients, before and after total knee arthroplasty (TKA), using 1H-magnetic resonance spectr...

Interoceptive pathways may be manipulated at various levels to develop interventions to improve symptoms in a range of disorders. Primarily through the lens of the respiratory system, we outline various pathways that can be manipulated at neural, behavioral, and psychological levels to change the representation of and attention to interoceptive sig...

Objective Acupuncture is a complex multi‐component treatment that has shown promise for the treatment of Fibromyalgia (FM), however, clinical trials have shown mixed results, possibly due to heterogeneous methodology and lack of understanding of the underlying mechanism of action. We sought to understand the specific contribution of somatosensory a...

Background Animal studies reported that vagus nerve stimulation increases noradrenalin release in target areas of the locus coeruleus (LC). Furthermore, after stimulation, animals exhibited improved retention performance. Evidence for memory improvement using transcutaneous vagus nerve stimulation (tVNS), a non‐invasive alternative, is scarce. Give...

Acupuncture consists of multiple components, and neuroimaging studies are beginning to tease apart potential brain-based mechanisms supporting this nonpharmacologic intervention. Brain imaging in patient populations is important for the acupuncture neuroimaging field, and recent studies have incorporated neuroimaging into a clinical trial framework...

Chronic low back pain (cLBP) has been associated with changes in brain plasticity. Non-pharmacological therapies such as Manual Therapy (MT) have shown promise for relieving cLBP. However, translational neuroimaging research is needed to understand potential central mechanisms supporting MT. We investigated the effect of MT on resting-state salienc...