Richard E Harris

• PhD
• Professor at University of California, Irvine

Objective Chronic low back pain (cLBP) is a common condition that impacts quality of life and function. There are many evidence-based treatments to address cLBP; however, treatment effects are modest, perhaps in part due to individual variation in treatment response. The Biomarkers for Evaluating Spine Treatments (BEST) Trial was designed as the co...

Background Pain remains a principal complaint for people with psoriatic arthritis (PsA), despite successful mitigation of inflammation. This situation alludes to the co-existence of distinct pain mechanisms. Nociceptive and nociplastic mechanisms are clinically challenging to distinguish. Advances in brain functional magnetic resonance imaging (fMR...

Objectives An emerging concept in the chronic pain literature, high-impact chronic pain (HICP), refers to pain that occurs very frequently and results in major disruption of daily life. Previous epidemiologic investigations have noted that lower educational attainment, age, and race appear to be associated with the frequency of HICP, but condition-...

The Acute to Chronic Pain Signatures (A2CPS) project is a large-scale, multi-site initiative aimed at identifying biomarkers and biosignatures that predict the transition from acute to chronic pain. The project is collecting multimodal, longitudinal data from over 2,500 individuals at risk for developing chronic pain after surgery. Here we describe...

Background: Pain is a life-long challenge for patients with sickle cell disease (SCD). Systemic inflammation and altered immune function have been associated with the pathogenesis of persistent pain in SCD. Acupuncture has shown significant promise in relieving SCD pain in both preclinical and clinical studies. However, our understanding of the imm...

Background: Sickle cell disease (SCD) is a genetic disorder characterized by chronic pain, inflammation, and recurrent vaso-occlusive crises (VOCs) associated with extremely painful episodes. Pain in SCD is often debilitating, impacting quality of life (QoL). Prior studies have identified altered functional connectivity (FC) in SCD, primarily throu...

Background: Sickle Cell Disease (SCD) is a genetic blood disorder that predominantly affects people of black descent. Individuals with SCD often experience chronic pain and recurrent vaso-occlusive crises (VOCs), requiring frequent hospitalization. The administration of high doses of opioids remains the primary therapy, increasing the risks of tole...

Sickle cell disease (SCD) is a genetic disorder causing painful and unpredictable Vaso-occlusive crises (VOCs) through blood vessel blockages. In this study, we propose explosive synchronization (ES) as a novel approach to comprehend the hypersensitivity and occurrence of VOCs in the SCD brain network. We hypothesized that the accumulated disruptio...

Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because thepathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Painbiomarkers could potentially identify and measure biological pathways and phenotypical expressions that arealtered by pain, provide insigh...

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients’ well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled be...

Objective To compare regional cortical thicknesses and subcortical gray matter volumes between children aged 9–10 years who play American football vs. non-contact sports. Design Secondary analysis of cross-sectional Adolescent Brain Cognitive Development (ABCD) Study data. Setting Multi-site study at 21 U.S. institutions. Participants 843 childr...

Background Pain is a common, debilitating, and poorly understood complication of sickle cell disease (SCD). The need for clinical pain management of SCD is largely unmet and relies on opioids as the main therapeutic option, which leads to a decreased quality of life (QoL). According to the literature, acupuncture has shown certain therapeutic effec...

Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. We measure the brain’s functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation p...

Background Sickle cell disease (SCD) leads to vaso-occlusive crises (VOCs) and increased healthcare use, disproportionately affecting Black/African Americans. Recruiting and retaining patients with SCD in clinical trials is challenging, with <5% participation rates (Masese et al., 2021) due to complexity, limited awareness, and socio-economic facto...

Purpose Sickle cell disease (SCD) is an inherited hemolytic disorder complicated by acute and chronic pain. Acute vasoocclusive crises (VOCs) associated with SCD are extremely painful episodes that are recurrent, unpredictable, and frequently require hospitalization and opioids for pain control. Changes in brain metabolites were identified in other...

Background Pain is a common, debilitating, and poorly understood complication of sickle cell disease (SCD). The need for clinical pain management of SCD is largely unmet and relies on opioids as the main therapeutic option, which leads to a decreased quality of life (QoL). According to the literature, acupuncture has shown certain therapeutic effec...

Objectives Cannabis is commonly used for chronic pain management, but cannabis’ effects remain poorly characterized in chronic nociplastic pain (NPP), which is posited to be caused by disturbances in nervous system pain processing. In this cross-sectional study (n=1,213), we used the 2011 Fibromyalgia (FM) Survey Criteria as a surrogate measure for...

Purpose: Overactive bladder (OAB) may be attributed to dysfunction in supraspinal brain circuits. Overactive bladder participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study reported sensations of urinary urgency during a bladder-filling paradigm while undergoing brain functional MRI to map supraspinal...

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...

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients’ well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled be...

Dietary supplements are commonly used among cancer survivors. Oncology providers rarely receive training about dietary supplements. We evaluated whether e-learning modules could improve oncology providers' dietary supplement knowledge. Oncology providers participated in the National Cancer Institute funded Integrative Oncology Scholars (IOS) progra...

Objective: Chronic pain has economic costs on par with cardiovascular disease, diabetes, and cancer. Despite this impact on the health care system and an increasing awareness of the relationship between pain and mortality, efforts to identify simple symptom-based risk factors for the development of pain, particularly in children, have fallen short...

Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide ins...

Background: Chronic low back pain is prevalent and disabling in Veterans, but effective pain management is challenging. Clinical practice guidelines emphasize multimodal pain management including evidence-based complementary and integrative health treatments such as acupressure as a first line of care. Unfortunately, the ability to replicate inter...

Urologic chronic pelvic pain syndrome (UCPPS) is a complex, debilitating condition in which patients often report nonpelvic pain in addition to localized pelvic pain. Understanding differential predictors of pelvic pain only vs widespread pain may provide novel pathways for intervention. This study leveraged baseline data from the Multidisciplinary...

A bstract Despite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. Identifying the impact of nitrous oxide on functional brain networks would advance understanding and contribute to the growing body...

The neurobiology of the psychedelic experience is not fully understood. Identifying common brain network changes induced by both classical (i.e., acting at the 5-HT2 receptor) and non-classical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state f...

Background and purpose: Many patients with chronic pain report hypersensitivity not only to noxious stimuli, but also to other modalities including innocuous touch, sound, and light, possibly due to differences in the processing of these stimuli. The goal of this study was to characterize functional connectivity (FC) differences between subjects w...

Objective: One aim of the Back Pain Consortium (BACPAC) Research Program is to develop an integrated model of chronic low back pain that is informed by combined data from translational research and clinical trials. We describe efforts to maximize data harmonization and accessibility to facilitate Consortium-wide analyses. Methods: Consortium-wid...

Evidence-based treatments for chronic low back pain (cLBP) typically work well in only a fraction of patients, and at present there is little guidance regarding what treatment should be used in which patients. Our central hypothesis is that an interventional response phenotyping study can identify individuals with different underlying mechanisms fo...

Microstructural alterations have been reported in patients with urologic chronic pelvic pain syndrome (UCPPS). However, it isn't clear whether these alterations are reproducible within 6 months or whether long-term symptom improvement is associated with specific microstructural changes. Using data from the MAPP-II Research Network, the current stud...

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the Multidisciplinary Approach to the study of chronic Pelvic Pain (MAPP) research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more s...

A bstract The neurobiology of the psychedelic experience is not fully elucidated. Identifying common brain network changes induced by both canonical (i.e., acting at the 5-HT2 receptor) and non-canonical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resti...

Management of patients suffering from low back pain (LBP) is challenging and requires development of diagnostic techniques to identify specific patient subgroups and phenotypes in order to customize treatment and predict clinical outcome. The Back Pain Consortium (BACPAC) Spine Imaging Working Group has developed standard operating procedures (SOPs...

Chronic pain produces the largest non-fatal burden of disease, yet our understanding of factors that contribute to the transition from acute chronic pain are poorly understood. The Acute to Chronic Pain Signatures Program (A2CPS) is a longitudinal, multi-site observational study to identify biomarkers (individual or biosignature combinations) that...

Chronic pain has become a global health problem contributing to years lived with disability and reduced quality of life. Advances in the clinical management of chronic pain have been limited due to incomplete understanding of the multiple risk factors and molecular mechanisms that contribute to the development of chronic pain. The Acute to Chronic...

Fibromyalgia (FM) is a chronic pain condition that is characterized by hypersensitivity to multimodal sensory stimuli, widespread pain, and fatigue. We have previously proposed explosive synchronization (ES), a phenomenon wherein a small perturbation to a network can lead to an abrupt state transition, as a potential mechanism of the hypersensitive...

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...

Fibromyalgia (FM) is a chronic pain condition that is characterized by hypersensitivity to multi-modal sensory stimuli, widespread pain, and fatigue. We have previously proposed explosive synchronization (ES), a phenomenon wherein a small perturbation to a network can lead to an abrupt state transition, as a potential mechanism of the hypersensitiv...

Objective There is increasing demand for prediction of chronic pain treatment outcomes using machine‐learning models, in order to improve suboptimal pain management. In this exploratory study, we used baseline brain functional connectivity patterns from chronic pain patients with fibromyalgia (FM) to predict whether a patient would respond differen...

Pain is the most common symptom experienced by patients with sickle cell disease (SCD) and is associated with poor quality of life. We investigated the association between grey matter volume (GMV) and the frequency of pain crises in the preceding 12 months and SCD-specific quality of life (QOL) assessed by the PedsQLTM SCD module in 38 pediatric pa...

Objectives Although primary motor cortex (M1) transcranial direct current stimulation (tDCS) has an analgesic effect in fibromyalgia (FM), its neural mechanism remains elusive. We investigated whether M1-tDCS modulates a regional temporal variability of blood-oxygenation-level-dependent (BOLD) signals, an indicator of the brain's flexibility and ef...

Altered brain structure and function is evident in adults with multisite chronic pain. Although many such adults trace their pain back to childhood, it has been difficult to disentangle whether central nervous system alterations precede or are consequences of chronic pain. If the former is true, aberrant brain activity may identify children vulnera...

Background Persistent cancer-related fatigue is one of the most common and burdensome symptoms experienced by ovarian cancer survivors. Despite the high burden of fatigue in ovarian cancer survivors, there are few available treatments. Previous research has shown self-acupressure to be a safe method for improving persistent fatigue, sleep, and qual...

Objective Acupuncture is a complex multicomponent treatment that has shown promise in 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. The present study was undertaken to understand the specific contributi...

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...

Kevin Boehnke and Richard E. Harris introduced a course in meditation, yoga and mindfulness to the neuroscience programme at their institution. Kevin Boehnke and Richard E. Harris introduced a course in meditation, yoga and mindfulness to the neuroscience programme at their institution.

Psychedelics have been recognized as model interventions for studying altered states of consciousness. However, few empirical studies of the shamanic state of consciousness, which is anecdotally similar to the psychedelic state, exist. We investigated the neural correlates of shamanic trance using high-density electroencephalography (EEG) in 24 sha...

Osteoarthritis (OA) is an extraordinarily prevalent and disabling disease [1]. Current management options for pain and functional limitation are constrained by modest efficacy or a range of unwanted side effects. Our society is being impacted through underemployment and the opioid epidemic and our health care systems are overstretched, as a consequ...

Neural circuitry regulating urine storage in humans has been largely inferred from fMRI during urodynamic studies driven by catheter infusion of fluid into the bladder. However, urodynamic testing may be confounded by artificially filling the bladder repeatedly at a high rate and examining associated time-locked changes in fMRI signals. Here we des...

Neuroimaging has enhanced our understanding of the neural correlates of pain. Yet, how neural circuits interact and contribute to persistent pain remain largely unknown. Here, we investigate the mesoscale organization of the brain through intrinsic functional communities generated from resting state functional MRI data from two independent datasets...

Despite the use of shamanism as a healing practice for several millennia, few empirical studies of the shamanic state of consciousness exist. We investigated the neural correlates of shamanic trance using high-density electroencephalography (EEG) in 24 shamanic practitioners and 24 healthy controls during rest, shamanic drumming, and classical musi...

Non-invasive measures of neuroinflammatory processes in humans could substantially aid diagnosis and therapeutic development for many disorders, including chronic pain. Several proton Magnetic Resonance Spectroscopy (H-MRS) metabolites have been linked with glial activity (i.e. choline and myo-inositol) and found to be altered in chronic pain patie...

Objective Rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) exhibit alterations in brain connectivity synonymous with central sensitization. This study was undertaken to investigate how peripheral inflammation, the principal nociceptive stimulus in RA, interacts with brain connectivity in RA patients with FM. Methods RA patient...

Objective: Chronic low back pain (CLBP) is associated with fatigue, pain, poor sleep, and disability. Acupressure is a low-risk treatment option used to manage symptoms in other groups, but its efficacy, particularly on fatigue and sleep, is unknown in CLBP. This study examined preliminary effects of two types of self-administered acupressure (rel...

Abstract Experimental pain sensitivity was assessed in individuals with urologic chronic pelvic pain syndrome (UCPPS) as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. A series of computer-controlled pressure stimuli were delivered to the thumbnail bed, an asymptomatic site distant from the area...

Objectives: Fatigue is a major burden among patients with RA, yet is poorly understood. We sought to conduct the first imaging study to investigate the neurobiological correlates of fatigue in RA and to improve upon the methodological limitations of previous neuroimaging studies that have investigated this symptom in other populations. Methods:...

Sickle cell disease (SCD) is a hemoglobinopathy affecting more than 100,000 individuals in the USA. Pain is the most common symptom experienced by patients with SCD. Understanding the central mechanisms underlying SCD pain is essential for developing future treatment strategies for these patients. Our recent studies in SCD using functional magnetic...

A critical component of brain network architecture is a robust hub structure, wherein hub regions facilitate efficient information integration by occupying highly connected and functionally central roles in the network. Across a wide range of neurological disorders, hub brain regions seem to be disrupted, and the character of this disruption can yi...

Pain is a complex phenomenon that may involve both peripheral and central neurobiological processes. Nociception is the unconscious registration of a noxious stimulus by the nervous system, while pain is a conscious experience. Neurobiological correlates of pain perception have been characterized from the initial point of tissue damage to its reali...

The Oxford Textbook of Neuroscience and Anaesthesiology is the first book of its kind to comprehensively address the care of neurosurgical and neurological patients, the study of neuroscience in anaesthesiology, and neurologic outcomes of non-neurosurgical interventions, which make up the ‘three pillars’ of neuroanesthesiology. The first section of...

Background Cancer survivors with fatigue often experience depressive symptoms, anxiety, and pain. Previously, we reported that self-acupressure improved fatigue; however, its impact on other co-occurring symptoms and their involvement in treatment action has not been explored. Methods Changes in depressive symptoms, anxiety, and pain were examined...

Objective The physiological mechanisms behind the therapeutic effects of spinal cord stimulation (SCS) are only partially understood. Our aim was to perform a literature review of studies that used objective measures to characterize mechanisms of action of SCS in neuropathic pain patients. Materials and Methods We searched the PubMed data base to...

Detecting covert consciousness in behaviorally unresponsive patients by brain imaging is of great interest, but a reproducible model and evidence from independent sources is still lacking. Here we demonstrate the possibility of using general anesthetics in a within-subjects study design to test methods or statistical paradigms of assessing covert c...

Objectives: Oncology providers are often confronted by patients who use complementary or alternative therapies, but have limited knowledge or confidence on how to advise patients on appropriate use. Despite this, there are few opportunities for oncology providers to learn about complementary or alternative therapies, while at the same time there i...

It is unknown how chronic inflammation impacts the brain. Here, we examined whether higher levels of peripheral inflammation were associated with brain connectivity and structure in 54 rheumatoid arthritis patients using functional and structural MRI. We show that higher levels of inflammation are associated with more positive connections between t...

Central sensitization refers to the amplification of pain by central nervous system mechanisms. Classically described as a consequence of ongoing nociceptive input, it is increasingly recognized that central sensitization also occurs independent of peripheral injury or inflammation. Features of central sensitization have been identified in nearly a...

Background: Despite its designation as a 'dissociative anaesthetic,' the dissociative and psychoactive effects of ketamine remain incompletely understood. The goal of this study was to characterise the subjective experiences and accompanying EEG changes with subanaesthetic doses of ketamine. Methods: High-density EEG was recorded in 15 human vol...

Objective: Moderate alcohol consumption has been associated with improved health outcomes including reduced risk of heart disease; however, less is known regarding alcohol's effects on chronic pain. The aim of this study was to assess associations between pain, fibromyalgia symptoms, and moderate alcohol use in a large chronic pain sample. Method...

Objectives: Many rheumatoid arthritis (RA) patients report pain despite excellent control of inflammation with immunotherapies. Variable degrees of co-existing fibromyalgia (FM) may explain this disparity. FM has been characterised by aberrant brain functional connectivity, especially between the Default Mode Network (DMN) and insula. We hypothesi...

Background: Acupuncture has a long history of relieving many forms of pain. However, many of acupuncture's mechanisms are still unknown and/or misunderstood. Objective: This review looks at past research on many different methods and targets of study related to acupuncture. The main focus is upon the importance of connective-tissue planes in and ar...

Conditioned pain modulation (CPM), a psychophysical paradigm that is commonly used to infer the integrity of endogenous pain-altering systems by observation of the effect of one noxious stimulus on another, has previously identified deficient endogenous analgesia in fibromyalgia (FM) and other chronic pain conditions. The mechanisms underlying this...