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Central Pain Mechanisms In The Rheumatic Diseases: Future Directions.

K. Phillips, D. Clauw
Published 2013 · Medicine

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Pain is a prominent component of many rheumatologic conditions, and is the result of a complex physiologic interaction of central and peripheral nervous system signaling that results in a highly individualized symptom complex. Pain is frequently categorized as acute or chronic (generally greater than three months duration). Chronic pain is not simply acute pain that has lasted longer, and is more likely to be influenced by input from the central nervous system, whereas acute pain is often attributable primarily to inflammation and/or damage in peripheral structures (i.e., nociceptive input). The prominent role of central factors in chronic pain is highlighted by the fact that there is currently no chronic pain condition in which the degree of tissue inflammation or damage alone (e.g., as measured by radiographs, magnetic resonance imaging (MRI), or endoscopy) accurately predicts the presence or severity of pain. Central factors alter pain processing by setting the “gain”, such that when peripheral input is present, it is processed against a background of central factors that can enhance or diminish the experience of pain. There are very large inter-individual differences in these central nervous system factors that influence pain perception, such that some individuals with significant peripheral nociceptive input (e.g. from joint damage or inflammation) will feel little or no pain, whereas others are very pain sensitive, and they can experience pain with minimal or no identifiable abnormal peripheral nociceptive input. This emerging knowledge has important implications for pain management in individuals with chronic rheumatologic disorders.
This paper references
Quality-of-Life Measurements Versus Disease Activity in Systemic Lupus Erythematosus
A. Kiani (2010)
Sensitization, glutamate, and the link between migraine and fibromyalgia
P. Sarchielli (2007)
Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia. Arthritis ResTher 2007;9:R110
G Vargas-Alarcon (2007)
: results from the 1958 British Birth Cohort Study
BI Nicholl (2010)
The relationship of anxiety and depression with self-reported knee pain in the community: data from the Baltimore Longitudinal Study of Aging.
P. Creamer (1999)
Understanding fibromyalgia: lessons from the broader pain research community.
D. Williams (2009)
A population-based twin study of functional somatic syndromes.
K. Kato (2009)
From fibrositis to functional somatic syndromes to a bell-shaped curve of pain and sensory sensitivity: evolution of a clinical construct.
K. Ablin (2009)
Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity
R. E. Sorge (2012)
Evidence-based data on pain relief with antidepressants
D. Fishbain (2000)
The relationship between fibromyalgia and interstitial cystitis.
D. Clauw (1997)
Work disability in systemic lupus erythematosus is prevalent and associated with socio-demographic and disease related factors
K. Baker (2009)
Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize ra patients with fibromyalgia.
F. Wolfe (2004)
Prediction of chronic post-operative pain: Pre-operative DNIC testing identifies patients at risk
D. Yarnitsky (2008)
Co-morbidities of patients with knee osteoarthritis.
K. W. Chan (2009)
Enhanced central pain processing of fibromyalgia patients is maintained by muscle afferent input: A randomized, double-blind, placebo-controlled study
R. Staud (2009)
How neuroimaging studies have challenged us to rethink: is chronic pain a disease?
D. Doleys (2010)
hypersensitivity states
DJ Clauw (1991)
processing of fibromyalgia patients is maintained by muscle afferent input : a randomized , double - blind , placebo - controlled study
G Affaitati (2009)
Learning from discordance in patient and physician global assessments of systemic lupus erythematosus disease activity.
C. Neville (2000)
Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms.
D. Clauw (1997)
Sensitization in patients with painful knee osteoarthritis
L. Arendt-Nielsen (2010)
Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain
J. Baraniuk (2004)
Osteoarthritis and sleep: the Johnston County Osteoarthritis Project.
K. Allen (2008)
Regional cerebral blood flow between primary and concomitant fibromyalgia patients: a possible way to differentiate concomitant fibromyalgia from the primary disease
J. Chen (2007)
Genetic variation in the beta2-adrenergic receptor but not catecholamine-O-methyltransferase predisposes to chronic pain: Results from the 1958 British Birth Cohort Study
L. Hocking (2010)
Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1.
M. Costigan (2010)
Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder.
L. Aaron (2000)
FibroCollective. A framework for fibromyalgia management for primary care providers
LM Arnold (2012)
A functional polymorphism in the catechol-O-methyltransferase gene is associated with osteoarthritis-related pain.
J. V. van Meurs (2009)
Fatigue in lupus is not correlated with disease activity.
B. Wang (1998)
The impact of momentary pain and fatigue on physical activity in women with osteoarthritis.
S. Murphy (2008)
Pain and rheumatology: thinking outside the joint.
D. Clauw (2009)
A 13-Week, Randomized Double-Blind, Placebo-Controlled, Cross-Over Trial of Ziprasidone in Bipolar Spectrum Disorder
A. Patkar (2015)
Role of the COMT gene Val158Met polymorphism in mental disorders: a review.
L. Hosák (2007)
Number of fibromyalgia tender points is associated with health status in patients with systemic lupus erythematosus
D. Buchwald
Modulatory influence on somatosensory perception from vibration and heterotopic noxious conditioning stimulation (HNCS) in fibromyalgia patients and healthy subjects
E. Kosek (1997)
The relationship between psychosocial variables and pain reporting in osteoarthritis of the knee.
P. Creamer (1998)
Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia
G. Vargas-Alarcón (2007)
Fibromyalgianess [editorial
F. Wolfe (2009)
Enhanced central
R Staud
Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli
L. Diatchenko (2006)
Chronic multisymptom illness affecting Air Force veterans of the Gulf War.
K. Fukuda (1998)
Prediction of chronic post - operative
D Yarnitsky
Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis.
I. J. Russell (1992)
Reduced insular γ-aminobutyric acid in fibromyalgia.
B. Foerster (2012)
Experimental and clinical applications of quantitative sensory testing applied to skin, muscles and viscera.
L. Arendt-Nielsen (2009)
Genetic basis for individual variations in pain perception and the development of a chronic pain condition.
L. Diatchenko (2005)
European Male Ageing Study Group. No evidence for a role of the catechol-O-methyltransferase pain sensitivity haplotypes in chronic widespread pain
BI Nicholl (2009)
Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: A 13-week, randomized, placebo-controlled trial
A. Chappell (2009)
The Overlap Between Fibromyalgia and Inflammatory Rheumatic Disease: When and Why Does it Occur?
D. Clauw (1995)
An epidemiologic study of fatigue with relevance for the chronic fatigue syndrome.
K. Fukuda (1997)
The induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states
C. Woolf (1991)
The role of stress in rheumatic diseases
A. Hassett (2010)
The relationship between disease activity, sleep, psychiatric distress and pain sensitivity in rheumatoid arthritis: a cross-sectional study
Y. Lee (2009)
Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia. Arthritis Rheum 2002;46:1333–43
RH Gracely (2002)
Idiopathic pain disorders – Pathways of vulnerability
L. Diatchenko (2006)
disorders — pathways of vulnerability
K Kato (2006)
Fatigue in systemic lupus erythematosus: contributions of disordered sleep, sleepiness, and depression.
A. Iaboni (2006)
Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome
H. Wilder (2007)
No evidence for a role of the catechol-O-methyltransferase pain sensitivity haplotypes in chronic widespread pain
B. Nicholl (2010)
Catechol O-methyltransferase haplotype predicts immediate musculoskeletal neck pain and psychological symptoms after motor vehicle collision.
S. McLean (2011)
A functional polymorphism in the catechol-Omethyltransferase gene is associated with osteoarthritis-related pain. Arthritis Rheum 2009;60:628–9
JB Van Meurs (2009)
Measurement of pain threshold in patients with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and healthy controls
E. Gerecz-Simon (2005)
The methodology of experimentally induced diffuse noxious inhibitory control (DNIC)-like effect in humans
D. Pud (2009)
Increased pressure pain sensibility in fibromyalgia patients is located deep to the skin but not restricted to muscle tissue
E. Kosek (1995)
Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty: a longitudinal voxel-based morphometric study.
S. Gwilym (2010)
Increased levels of neurotrophins are not specific for chronic migraine: evidence from primary fibromyalgia syndrome.
P. Sarchielli (2007)
Quantitative Sensory Testing in Vulvodynia Patients and Increased Peripheral Pressure Pain Sensitivity
Jutta Giesecke (2004)
Corrigendum to “Genetic variation in the beta2-adrenergic receptor but not catecholamine-O-methyltransferase predisposes to chronic pain: Results from the 1958 British Birth Cohort Study” [Pain 149 (2010) 143–151]
Lynne J. Hocking (2010)
Altered heat pain thresholds and cerebral event-related potentials following painful CO2 laser stimulation in subjects with fibromyalgia syndrome
S. Gibson (1994)
Fibromyalgia: an overview.
D. Clauw (2009)
The Voltage-Gated Sodium Channel Nav1.9 Is an Effector of Peripheral Inflammatory Pain Hypersensitivity
F. Amaya (2006)
Power spectral analysis of sleep EEG in twins discordant for chronic fatigue syndrome.
R. Armitage (2009)
Distinguishing fibromyalgia from rheumatoid arthritis and systemic lupus in clinical questionnaires: an analysis of the revised Fibromyalgia Impact Questionnaire (FIQR) and its variant, the Symptom Impact Questionnaire (SIQR), along with pain locations
Ronald Friend (2011)
The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort. Arthritis Rheum 2005;52:1577–84
T Giesecke (2005)
Antecedent nonbladder syndromes in case-control study of interstitial cystitis/painful bladder syndrome.
J. Warren (2009)
Functional imaging of pain in patients with primary fibromyalgia.
D. Cook (2004)
Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain
W. Maixner (1995)
, fatigue , and sleep disturbance and improves functionality in fibromyalgia : results from a 14 - week , randomized , double - blind , placebo - controlled study
DJ Clauw (2011)
Evidence of augmented central pain processing in idiopathic chronic low back pain.
T. Giesecke (2004)
Functional magnetic resonance imaging evidence of augmented pain processing in fibromyalgia.
R. Gracely (2002)
Pain genes?: natural variation and transgenic mutants.
J. Mogil (2000)
Pain inhibition is deficient in chronic widespread pain but normal in major depressive disorder.
Edith Normand (2011)
Interoception: the sense of the physiological condition of the body
A. Craig (2003)
Fibromyalgia is a major contributor to quality of life in lupus.
D. Gladman (1997)
erythem - atosus
R Friend (1994)
Increased rates of fibromyalgia following cervical spine injury. A controlled study of 161 cases of traumatic injury.
D. Buskila (1997)
Association between radiographic features of knee osteoarthritis and pain: results from two cohort studies
T. Neogi (2009)
Depression and pain comorbidity: a literature review.
M. Bair (2003)
Neural correlates of interindividual differences in the subjective experience of pain
R. Coghill (2003)
Pain Mechanisms in Osteoarthritis: Understanding the Role of Central Pain and Current Approaches to Its Treatment
P. Mease (2011)
Increased Sensitivity to Thermal Pain Following a Single Opiate Dose Is Influenced by the COMT val158met Polymorphism
K. Jensen (2009)
Cerebral Activation in Patients With Irritable Bowel Syndrome and Control Subjects During Rectosigmoid Stimulation
B. Naliboff (2001)
Unexplained Symptoms After Terrorism and War: An Expert Consensus Statement
D. Clauw (2003)
The development of fibromyalgia – I: Examination of rates and predictors in patients with rheumatoid arthritis (RA)
F. Wolfe (2011)
Preclinical and early clinical investigations related to monoaminergic pain modulation
K. Bannister (2011)
Diffuse Noxious Inhibitory Controls (DNIC) in Animals and in Man
D. Le Bars (1991)
The prevalence and associations of sleep disturbances in patients with systemic lupus erythematosus
P. Chandrasekhara (2009)
The role of the central nervous system in the generation and maintenance of chronic pain in rheumatoid arthritis, osteoarthritis and fibromyalgia
Y. Lee (2011)
Importance of genetic influences on chronic widespread pain.
Kenji Kato (2006)
Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta‐analysis
T. Tzellos (2010)
Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews.
K. Kroenke (2009)
Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients.
S. Gwilym (2009)
Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition
Nancy Julien (2005)
Human brain mechanisms of pain perception and regulation in health and disease
A. Apkarian (2005)
Peripheral and central nervous changes in patients with rheumatoid arthritis in response to repetitive painful stimulation.
T. Hummel (2000)
The prevalence and clinical impact of fibromyalgia in systemic lupus erythematosus.
G. D. Middleton (1994)
The relationship between antidepressant and analgesic responses: findings from six placebo-controlled trials assessing the efficacy of duloxetine in patients with major depressive disorder.
D. Fishbain (2008)
Fibromyalgia Syndrome and Disease Activity in Systemic Lupus Erythematosus
E. Morand (1994)
Etiology of fibromyalgia: the possible role of infection and vaccination.
D. Buskila (2008)
Epidemiology of osteoarthritis.
T. Neogi (2013)
Somatosensory perception in a remote pain‐free area and function of diffuse noxious inhibitory controls (DNIC) in patients suffering from long‐term trapezius myalgia
A. Leffler (2002)
Effects of treatment of peripheral pain generators in fibromyalgia patients
G. Affaitati (2011)
Outcome and Predictor Relationships in Fibromyalgia and Rheumatoid Arthritis: Evidence Concerning the Continuum versus Discrete Disorder Hypothesis
F. Wolfe (2009)
Lack of pressure pain modulation by heterotopic noxious conditioning stimulation in patients with painful osteoarthritis before, but not following, surgical pain relief
E. Kosek (2000)
Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee.
M. Hannan (2000)
Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: Do conditioning stimulus painfulness, gender and personality variables matter?
M. Granot (2008)
Measures of disease activity and damage in SLE.
M. Urowitz (1998)
Increased pain sensitivity of the upper extremities of TMD patients with myalgia to experimentally-evoked noxious stimulation: possibility of worsened endogenous opioid systems.
K. Kashima (1999)
Report of the American College of Rheumatology Pain Management Task Force
D. Borenstein (2010)
Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome.
I. J. Russell (1994)
Potential genetic risk factors for chronic TMD: genetic associations from the OPPERA case control study.
S. Smith (2011)
A framework for fibromyalgia management for primary care providers.
L. Arnold (2012)
Individual differences in diffuse noxious inhibitory controls (DNIC): association with clinical variables
R. Edwards (2003)
The health consequences of the first Gulf war
D. Clauw (2003)
Tolerance for rectosigmoid distention in irritable bowel syndrome.
W. E. Whitehead (1990)
Sodium oxybate reduces pain, fatigue, and sleep disturbance and improves functionality in fibromyalgia: Results from a 14-week, randomized, double-blind, placebo-controlled study
I. J. Russell (2011)
Comparison of hip and knee arthroplasty outcomes at early and intermediate follow-up.
S. O'brien (2009)
Central sensitization: Implications for the diagnosis and treatment of pain
C. Woolf (2011)
COMT val158met Genotype Affects µ-Opioid Neurotransmitter Responses to a Pain Stressor
J. Zubieta (2003)
Regulation of human affective responses by anterior cingulate and limbic mu-opioid neurotransmission.
J. Zubieta (2003)
GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence
I. Tegeder (2006)
Decreased Central μ-Opioid Receptor Availability in Fibromyalgia
R. Harris (2007)
Functional imaging of brain responses to pain. A review and meta-analysis (2000)
R. Peyron (2000)
Comment on Diatchenko et al. Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain-evoking stimuli. Pain 2006;125:216–24
H. Kim (2007)
thresholds and cerebral event - related potentials following painful CO 2 laser stimulation in subjects with fibromyalgia syndrome
E Kosek (1994)
The relationship between depression, clinical pain, and experimental pain in a chronic pain cohort.
T. Giesecke (2005)
Co-morbidities of patients with knee osteoarthritis.
Chan Kw (2009)
Why does osteoarthritis of the knee hurt--sometimes?
P. Creamer (1997)

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Type, rather than number, of mental and physical comorbidities increases the severity of symptoms in patients with irritable bowel syndrome.
J. Lackner (2013)
Functional reorganisation in chronic pain and neural correlates of pain sensitisation: A coordinate based meta-analysis of 266 cutaneous pain fMRI studies
R. Tanasescu (2016)
Evaluating the psychometric properties of the Widespread Pain Index and the Symptom Severity Scale in youth with painful conditions
Joanne Dudeney (2019)
Association of rheumatic diseases with symptom severity, quality of life, and treatment outcome in patients with fibromyalgia
Juan Jiao (2016)
Reflecting on pain management for patients with osteoarthritis and other rheumatic disorders: there's more to pain management than managing pain.
Danielle Perret (2013)
Changes in inflammatory plasma proteins from patients with chronic pain associated with treatment in an interdisciplinary multimodal rehabilitation program – an explorative multivariate pilot study
B. Gerdle (2019)
Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of biological therapy: a cross-sectional study
P. R. Lage-Hansen (2016)
Fibromyalgia and Centralized Pain States
Chad M Brummett (2018)
Nociceptin/orphanin FQ opioid peptide (NOP) receptor and &mgr;‐opioid peptide (MOP) receptors both contribute to the anti‐hypersensitive effect of cebranopadol in a rat model of arthritic pain
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Involvement of Peripheral and Spinal Tumor Necrosis Factor α in Spinal Cord Hyperexcitability During Knee Joint Inflammation in Rats
C. Koenig (2014)
Reflections on ‘older’ drugs: learning new lessons in rheumatology
S. Kerrigan (2020)
Musculoskeletal manifestations of tuberculosis: An observational study
Nikhil Gupta (2018)
Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer.
N. Henry (2014)
Two sides on the fibromyalgia coin: physical pain and social pain (invalidation)
Banafsheh Ghavidel-Parsa (2020)
The management of fibromyalgia from a psychosomatic perspective: an overview
F. Sancassiani (2017)
Avaliação dos efeitos da imersão diária em água termomineral de Caldas da Imperatriz-SC na inflamação periférica em camundongos
Fernanda Madeira (2016)
Work Ability in Fibromyalgia: An Update in the 21st Century
A. Palstam (2017)
Editorial: Fibromyalgia: A Never‐Ending Story of Central and Peripheral Pain Mechanisms
P. Sarzi-Puttini (2014)
Diclofenac attenuates inflammation through TLR4 pathway and improves exercise performance after exhaustive swimming.
F. M. Steckling (2019)
Patient-Reported Outcomes Measurement Information System (PROMIS) instruments among individuals with symptomatic knee osteoarthritis: a cross-sectional study of floor/ceiling effects and construct validity
J. Driban (2015)
Improvement in the Spatial Distribution of Pain, Somatic Symptoms, and Depression After a Weight Loss Intervention.
A. Schrepf (2017)
The sources of pain in osteoarthritis: a pathophysiological review.
F. Salaffi (2014)
Chronic widespread pain and fibromyalgia from the perspective of rehabilitation Aspects of clinical assessment and management
U. Wewer (2016)
Novel Insights into the Pathophysiology and Treatment of Fibromyalgia
Bente Danneskiold-Samsøe (2014)
Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; characteristics, antecedents and sequelae
Daniel F. McWilliams (2019)
Attitudes of Israeli Rheumatologists to the Use of Medical Cannabis as Therapy for Rheumatic Disorders
Jacob N Ablin (2016)
Dynamic weight bearing is an efficient and predictable method for evaluation of arthritic nociception and its pathophysiological mechanisms in mice
A. U. Quadros (2015)
Fibromyalgia: Timely diagnosis and treatment options.
Yvonne Dʼarcy (2016)
Fibromyalgia and Chronic Pain Syndromes
L. Arnold (2016)
Temporal dynamics of pain: an application of regime-switching models to ecological momentary assessments in patients with rheumatic diseases
Stefan Schneider (2018)
Fibromyalgia-Like Syndrome Associated with Parkinson’s Disease—A Cohort Study
Ran Abuhasira (2019)
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