Richard Gracely

University of North Carolina at Chapel Hill | UNC · Center for Pain Research and Innovation

The study presents a novel approach of programing pain inhibition in chronic pain patients based on the hypothesis that pain perception is modulated by dysfunctional dorsal medial nucleus tractus solitarii (dmNTS) reflex arcs that produce diminished baroreflex sensitivity (BRS) resulting from a conditioned response. This study tested whether admini...

Objective To determine the incidence and worsening of lumbar spine structure and low back pain (LBP) and whether they are predicted by demographic characteristics or clinical characteristics or appendicular joint osteoarthritis (OA). Methods Paired baseline (2003‐2004) and follow‐up (2006‐2010) lumbar spine radiographs from the Johnston County Ost...

Objective Determine if associations between demographic, appendicular joint osteoarthritis (OA), clinical characteristics reflect different phenotypes of OA in the lumbar spine. Methods Participants were from the Johnston County OA Project. Demographics consisted of age, sex, and race (White and African American [AA]) and clinical characteristics...

Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide ass...

Aim An intrinsic pain regulatory system is modulated by both cardiovascular dynamics that influence baroreflex sensitivity (BRS) and diminished in Fibromyalgia (FM). Baroreceptors relay cardiovascular output to the dorsal medial nucleus tractus solitarius reflex arcs that regulate pain, sleep, anxiety, and blood pressure. This study evaluated the e...

Perspective: This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo...

Das folgende Kapitel beschäftigt sich mit dem Krankheitsbild der Fibromyalgie, seiner biomedizinischen und psychosozialen Diagnostik sowie der Pharmakotherapie, Physiotherapie und insbesondere der psychologischen Schmerztherapie. Die im Zusammenhang mit der Erkrankung am häufigsten verwendeten psychodiagnostischen Verfahren werden vorgestellt, eben...

Objective: To assess differences in vulvar and peripheral sensitivity between women with and without vulvodynia. Methods: Women with vulvodynia (n = 41) and age-matched controls (n = 43) seen in the outpatient setting were evaluated via surveys, clinical examination, and multimodal sensory testing (pressure, heat, cold, vibration, and electrical...

Introduction Application of noxious stimulation to one body area reduces pain sensitivity in a remote body area through activation of an endogenous pain-inhibitory network, a behavioral phenomenon referred to as conditioned pain modulation (CPM). The efficiency of CPM is predictive of a variety of health outcomes, while impaired CPM has been associ...

Introduction Transobturator slings can be successfully used to treat stress urinary incontinence and improve quality of life through a minimally invasive vaginal approach. Persistent postoperative pain can occur and pose diagnostic and therapeutic dilemmas. Following a sling procedure, a patient complained of pinching clitoral and perineal pain. He...

Background: Determination of psychophysiological effects of operant behavioural (OBT) and cognitive behavioural treatment (CBT) for fibromyalgia patients. Methods: One hundred and fifteen female patients randomized to OBT (N = 43), CBT (N = 42), or whole-body infrared heat (IH) (N = 30) were compared before and after group treatment as well as a...

The MPQs have greatly advanced the field of pain evaluation and identified a number of issues. Summary scores confound the breadth and magnitude of pain experience and depend on the fit of the descriptors to the particular pain. The 3 major dimensions are well established. The affective dimension represents a broad field of psychological evaluation...

The subjective experience of cognitive dysfunction (“fibrofog”) is common in fibromyalgia. This study investigated the relation between subjective appraisal of cognitive function, objective cognitive task performance, and brain activity during a cognitive task using functional magnetic resonance imaging (fMRI). Sixteen fibromyalgia patients and 13...

Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of...

Central sensitivity syndromes (CSS) share features of similar multiple symptoms, virtually unknown mechanisms and lack of effective treatments. The CSS nomenclature was chosen over alternatives because it focused on a putative physiological mechanism of central sensitization common to disorders such as fibromyalgia, irritable bowel syndrome, vulvod...

There is growing awareness that dyspnoea, like pain, is a multidimensional experience, but measurement instruments have not kept pace. The Multidimensional Dyspnea Profile (MDP) assesses overall breathing discomfort, sensory qualities, and emotional responses in laboratory and clinical settings. Here we provide the MDP, review published evidence re...

This study examined the relationship of psychophysiological response patterns in fibromyalgia (FM) with psychological characteristics and comorbid mental disorders. Surface electromyographic data (EMG), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), and skin conductance levels (SCL) were recorded continuously during baseline, s...

The poster presents the effects of a new treatment method ”Systolic Extinction Training” SET in comparison to a SHAM / Placebo treatment.

The poster presents a method to initiate inhibition of chronic pain by activating the barorefelx sensitivity (BRS). We concluded: Despite diminished BRS in FM, the combination of electrical painful and non-painful stimuli applied during specific phases of the cardiac cycle diminished pain sensitivity and reduced fibromyalgia pain. Pain and stress r...

Antidepressant drugs are commonly used to treat fibromyalgia but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controll...

Objective: To determine the association between generalized evoked pressure pain sensitivity with distal pressure-pain threshold (PPT) and the presence, severity, or number of involved knee/hip joints with radiographic osteoarthritis (rOA) or related symptoms. Methods: Data for these cross-sectional analyses come from the second followup (2008-1...

Central sensitization elicits pain hypersensitivity and is thought to be causally implicated in painful temporomandibular disorder (TMD). This causal inference is based on cross-sectional evidence that people with TMD have greater sensitivity than controls to noxious stimuli. We tested this inference in the OPPERA prospective cohort study of 3,258...

Research suggests that varied etiologic factors are responsible for burning mouth syndrome (BMS). We examined the role of immune and endocrine function in the pathology of BMS. We conducted a case-control study to evaluate immune (lymphocyte subpopulations) and endocrine (hypothalamus-pituitary-adrenal axis and sympathetic-adrenomedullary system) f...

Exposure to acute 'stressors' (e.g. infections, pain, trauma) often results in altered sleep habits and reductions in routine activity. In some individuals, these behavioural responses to acute stressors may contribute to the development of chronic somatic symptoms such as widespread pain, fatigue, memory difficulties and mood disturbances, much li...

Objective There is vast evidence to support the presence of brain aberrations in patients with fibromyalgia (FM), and it is possible that central plasticity is critical for the transition from acute to chronic pain. The aim of the present study was to investigate the relationship between brain structure and function in patients with FM. Methods Fun...

To investigate for differences in metabolic concentrations and ratios between patients with systemic lupus erythematosus (SLE) without (group SLE) and those with neurological symptoms (group NPSLE) compared to a healthy control (group HC) in three normal-appearing brain regions: the frontal white matter, right insula (RI), and occipital gray matter...

Quantitative sensory testing (QST) is a psychophysical method used to quantify somatosensory function in response to controlled stimuli in healthy subjects and patients. Although QST shares similarities with the quantitative assessment of hearing or vision, which is extensively used in clinical practice and research, it has not gained a large accep...

Four rats were trained to press a lever to escape from high-intensity (.5 mA) and low-intensity (.25-mA) electric shock, and then the intensity of the shock was alternated in blocks of 30 trials within sessions. The animals escaped more rapidly from the high-intensity shock than from the low-intensity shock. Performance adjustments following an inc...

Unlabelled: Vulvodynia (VVD) is a chronic pain disorder wherein women display sensitivity to evoked stimuli at the vulva and/or spontaneous vulvar pain. Our previous work suggests generalized hyperalgesia in this population; however, little is known about central neurobiological factors that may influence pain in VVD. Here we investigated local (v...

Background In recent years, the prescription of serotonin-noradrenalin reuptake inhibitors (SNRIs) for treatment of fibromyalgia (FM) has increased with reports of their efficacy. The SNRI milnacipran is approved by the U.S. Food and Drug Administration (FDA) for treatment of FM, yet, the mechanisms by which milnacipran reduces FM symptoms are unkn...

Fibromyalgia (FM) pathophysiology remains largely unknown, with considerable neuroimaging evidence that brain functional and structural characteristics of patients differ from those of controls. Studies using diffusion tensor imaging (DTI) to assess white matter (WM) microstructure have shown significant differences across several brain regions for...

Psychophysical evaluations of evoked pain sensations target two dimensions - intensity or unpleasantness. This study developed alternative, behavioral measures of unpleasantness by directly matching two stimulus modalities. In each of two paradigms, subjects receive both an aversive non-nociceptive stimulus (loud sound) and painful blunt pressure a...

Objectives: To evaluate the feasibility of a randomized-controlled trial and to obtain estimates of the effects of combined cognitive-behavioral therapy (CBT) and milnacipran for the treatment of fibromyalgia. Methods: Fifty-eight patients with fibromyalgia were randomized to 1 of the 3 treatment arms: (1) combination therapy (n = 20); (2) milna...

Headache medicine is primarily dependent on patients' subjective reports of pain, which are assessed at diagnosis and throughout the duration of treatment. There is a need for an objective, quantitative biological measurement of headache pain severity. In this study, quantitative sensory testing (QST) was conducted via multi-site vibrotactile stimu...

Widespread musculoskeletal pain is the hallmark symptom reported by fibromyalgia patients. Such pain presents in a continuous and rarely remitting fashion, and current understanding of its pathophysiology is limited. By means of resting functional magnetic resonance imaging (fMRI) using blood oxygen-level dependent signal, recent studies showed imb...

Fibromyalgia and depression might represent two manifestations of affective spectrum disorder. They share similar pathophysiology and are largely targeted by the same drugs with dual action on serotoninergic and noradrenergic systems. Here, we review evidence for genetic and environmental factors that predispose, precipitate, and perpetuate fibromy...

Fibromyalgia is characterized by chronic widespread pain, clinical symptoms that include cognitive and sleep disturbances, and other abnormalities such as increased sensitivity to painful stimuli, increased sensitivity to multiple sensory modalities, and altered pain modulatory mechanisms. Here we relate experimental findings of fibromyalgia sympto...

Fibromyalgia is characterized by widespread pain and tenderness; however, comorbid cognitive difficulties are a common complaint among patients. Known as fibro fog or dyscognition, this symptom comprises difficulties with complex cognitive processes including memory, executive function, concentration and attention. While the mechanisms that initiat...

Unlabelled: Vestibulodynia, the most common type of chronic vulvovaginal pain, impairs the psychological, physical health of nearly 10% of women at some point in their lifetime. The aim of this investigation was to establish reliable standardized methodologies for assessment of pain sensitivity in vulvar mucosa and pelvic musculature. We enrolled...

Background: There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome (FM). In order to fully understand the mechanisms involved in FM pathology, there is a need for closer investigation of endogenous pain modulation. In the present study, we compared the functional connectivity of the desc...

Temporomandibular disorders (TMD) include craniocervical pain conditions with unclear etiologies. Central changes are suspected; however, few neuroimaging studies of TMD exist. Single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) was used before and after pressure-pain testing to assess glutamate (Glu), glutamine (Gln), N-acetylaspartate...

Little is known about the effects of successful treatment on brain function in chronic pain. This study examined changes in pain-evoked brain activation following behavioral extinction training in fibromyalgia patients. Using functional magnetic resonance imaging, brain activation to painful mechanical stimuli applied to the 2nd phalanx of the left...

Fibromyalgia (FM) represents a complex disorder that is characterized by widespread pain and tenderness and is frequently accompanied by additional somatic and cognitive/affective symptoms. Genetic risk factors are known to contribute to the etiology of the syndrome. The aim of this study was to examine >350 genes for association with FM, using a l...

Most measures of dyspnea assess a single aspect (intensity or distress) of the symptom. We developed the Multidimensional Dyspnea Profile (MDP) to measure qualities and intensities of the sensory dimension and components of the affective dimension. The MDP is not indexed to a particular activity and can be applied at rest, during exertion, or durin...

Chronic back pain continues to be a major cause of distress, disability, work loss, and a huge cost to society. This resource examines the risk factors and mechanisms involved in the transition from acute to chronic back pain. It integrates genetic, biomechanical, neurobiological, psychophysiological, psychosocial, and socieconomic risk factors.

Ever since it was first defined, fibromyalgia (FM) has been considered one of the most controversial diagnoses in the field of rheumatology, to the point that not everybody accepts its existence as an independent entity. The sensitivity and specificity of the proposed diagnostic criteria are still debated by various specialists (not only rheumatolo...

Fibromyalgia syndrome (FM) is a common chronic pain condition that affects at least 2% of the adult population. Chronic widespread pain is the defining feature of FM, but patients may also exhibit a range of other symptoms, including sleep disturbance, fatigue, irritable bowel syndrome, headaches, and mood disorders. The etiology of FM is not compl...

Fibromyalgia syndrome (FMS) is a common chronic condition of widespread pain with causal mechanisms that are largely unknown. It is characterized by moderate to severe musculoskeletal pain and allodynia, but its pathogenesis appears confined to the nociceptive structures of the central nervous system. FMS is often triggered by negative environmenta...

Fibromyalgia (FM) is a rheumatic disease characterized by musculoskeletal pain, chronic diffuse tension and/or stiffness in joints and muscles, easy fatigue, sleep and emotional disturbances, and pressure pain sensitivity in at least 11 of 18 tender points. At present, there are no instrumental tests or specific diagnostic markers for FM; in fact,...

Pharmacological treatment has been gradually enriched by a variety of compounds; however, no single drug is capable of fully managing the constellation of fibromyalgia (FM) symptoms. Currently, it is not possible to draw definite conclusions concerning the best pharmacological approach to managing FM because results of randomized clinical trials pr...

Fibromyalgia is a complex syndrome associated with significant impairment in quality of life and function and with substantial financial costs. Once the diagnosis is made, providers should aim to increase patients' function and minimize pain. Fibromyalgia patients frequently use alternative therapies, strongly indicating both their dissatisfaction...

There many open questions concerning the concept of primary prevention in FM. Diagnostic or classification criteria are not universally accepted, and this leads to difficulties in establishing the onset and duration of the disease. In the case of FM, primary prevention may consist of the immediate care of acute pain or treatment for affective distu...

The underlying mechanisms of many pain conditions are not known and many conditions have no effective treatment. Modern dynamic neuroimaging have increased the understanding of altered CNS processing in different pain conditions. This chapter describes the use of advanced MR imaging techniques like fMRI, MR spectroscopy, and diffusion-weighted imag...

Fibromyalgia (FM) is a chronic pain condition characterized by widespread musculoskeletal pain, tenderness to pressure, and a constellation of symptoms such as fatigue, sleep difficulties, and cognitive dysfunction. Experimental and anecdotal evidence suggests: a) modest correlation between sensitivity to painful heat and pressure; b) influence of...

The primary symptom of fibromyalgia is widespread pain. This symptom is accompanied by secondary symptoms, such as cognitive difficulties and sensitivity to painful stimulation, and by numerous co-morbidities. The first neuroimaging studies addressed the primary symptom by examining differences between patients and controls using single-photon-emis...

There is emerging evidence that transcranial magnetic stimulation (TMS) can produce analgesic effects in clinical samples and in healthy adults undergoing experimentally induced pain; and the field of minimally invasive brain stimulation for the management of pain is expanding rapidly. Although motor cortex is the most widely used cortical target f...

Das folgende Kapitel beschäftigt sich mit dem Krankheitsbild der Fibromyalgie, seiner biomedizinischen und psychosozialen Diagnostik sowie der Pharmakotherapie, Physiotherapie und insbesondere der psychologischen Schmerztherapie. Die im Zusammenhang mit der Erkrankung am häufigsten verwendeten psychodiagnostischen Verfahren werden vorgestellt, eben...

The prefrontal cortex may be a promising target for transcranial magnetic stimulation (TMS) in the management of pain. It is not clear how prefrontal TMS affects pain perception, but previous findings suggest that ventral lateral and medial prefrontal circuits may comprise an important part of a circuit of perceived controllability regarding pain,...

Mood disturbance is common among patients with fibromyalgia (FM), but the influence of psychological symptoms on pain processing in this disorder is unknown. We undertook the present study to investigate the differential effect of depressive symptoms, anxiety, and catastrophizing on 1) pain symptoms and subjective ratings of general health status a...

Objectives: The etiologies and pathophysiologies of chronic myofascial temporomandibular disorders (TMD) are not well understood. Using functional magnetic resonance imaging (fMRI), we previously demonstrated unique central activation patterns in TMD subjects. The present study follows up on these demonstrations with proton magnetic resonance spect...

The experience of pain serves two primary purposes, both critical for survival. Pain is foremost a warning signal, protecting the organism from harm or at least minimizing injury. Pain receptors, or nociceptors, are widespread. An extensive network of nociceptors can signal damage from anyplace on the skin, or in deeper tissues including muscles an...

This article considers four broad classes of psychological techniques and their effects on fibromyalgia (FM) pain. A literature search identified 14 randomized controlled trials (RCTs) of cognitive-behavioral therapy (CBT) and operant-behavioral therapy (OBT), five relaxation RCTs, five biofeedback RCTs, five hypnotherapy RCTs, and two writing inte...

Controversy remains regarding the mechanisms of acupuncture analgesia. A prevailing theory, largely unproven in humans, is that it involves the activation of endogenous opioid antinociceptive systems and mu-opioid receptors (MORs). This is also a neurotransmitter system that mediates the effects of placebo-induced analgesia. This overlap in potenti...

Functional MRI blood oxygenation level dependent activation studies on patients who have fibromyalgia have demonstrated augmented sensitivity to painful pressure and the association of this augmentation with variables such as depression and catastrophizing and have also been used to evaluate the symptoms of cognitive dysfunction. Using a wide array...

Although dyspnea is a common and troubling symptom, our understanding of the neurophysiology of dyspnea is woefully incomplete. Most measurements of dyspnea treat it as a single entity. Although the multidimensional dyspnea concept has been mentioned for many decades, only recently has the concept been the subject of experimental tests. Emerging ev...

Over the years, many have viewed Fibromyalgia syndrome (FMS) as a so-called "functional disorder" and patients have experienced a concomitant lack of interest and legitimacy from the medical profession. The symptoms have not been explained by peripheral mechanisms alone nor by specific central nervous system mechanisms. In this study, we objectivel...

Temporomandibular disorders (TMD) are poorly understood. Although symptoms are located in masticatory muscles and/or temporomandibular joints, peripheral structures do not appear to be the primary cause of symptoms. This has led to the hypotheses that TMD involve changes in pain processing, that can be identified using experimental pain testing and...

Fibromyalgia (FM) is a chronic widespread pain condition that is often accompanied by comorbid negative mood states including stress and depression. Positron emission tomography (PET) studies have demonstrated alterations in central -opioid receptor (MOR) availability in fibromyalgia patients as well as patients diagnosed with major depressive diso...

Clinical trials of acupuncture for the treatment of chronic pain conditions such as fibromyalgia (FM) have resulted in equivocal findings. In most studies, traditional acupuncture and sham acupuncture are equally effective. However no study has used functional magnetic resonance imaging (fMRI) in FM patients to examine more detailed changes in cent...

Co-morbid conditions are common among persons with chronic pain, and assessment of these conditions may be beneficial in the evaluation and treatment of pain. The Complex Medical Symptoms Inventory (CMSI) is a 52-item inventory that measures presence or absence of persistent physical symptoms (lasting at least 3 months) over the past year and durin...

Chronic pain disorders such as fibromyalgia (FM) are often precipitated by a stressful event (e.g., motor vehicle accident) that prevents normal sleep and exercise. We hypothesize that stressors disrupt regular sleep and exercise routines, and that this leads to increased pain and other symptoms. Furthermore, we hypothesize that individuals are not...