Central Pain Syndrome

Earn CME/CE in your profession:

Continuing Education Activity

Central sensitization of pain occurs when the patient's nervous system is persistently in a state of high activity. This state decreases sensitivity to fire action potentials. When this happens, though the peripheral nervous system provides limited input, the central nervous system is responding as if there have been many painful stimuli. This chapter reviews the evaluation and treatment of central pain syndrome and highlights the healthcare team's role in managing patients with this condition.


  • Identify the etiology and epidemiology of central pain syndrome.
  • Review the appropriate elements of a physical exam to evaluate central pain syndrome properly.
  • Outline the management options available for central pain syndrome.
  • Describe some inter-professional team strategies for improving care coordination and communication to improve outcomes for patients with central pain syndrome.


Central sensitization of pain occurs when the patient's nervous system is persistently in a high activity state, which decreases sensitivity to fire action potentials. When this happens, though the peripheral nervous system provides limited input, the central nervous system is responding as if there has been a high level of painful stimuli. An increase in firing of action potential leads to an amplification of neural signaling. Patients become hypersensitive to pain. This state of high alert is commonly known as the wind-up; clinically, it is known at temporal summation. Ordinary touch may reproduce pain (allodynia), or potentially painful stimulus appear worse (hyperalgesia).[1] The pain can be made even worse by cold temperatures and changes in an emotional state. 

Central pain syndrome is also known as centralized pain, central pain, central sensitization, and widespread or diffuse pain. It is relatively common and has both genetic and environmental influences that predispose patients. Patients with multiple chronic disease states can experience both localized pain and centralized pain. Centralized pain often occurs in patients who have fibromyalgia and chronic pain syndrome, and it also presents following neurological injuries such as a stroke or a spinal cord injury. Healthcare providers need to be able to identify who is at risk for centralized pain.

Centralized pain is associated with memory loss and worsening anxiety. The treatment of central pain is different from nociceptor pain. It often requires patients to take antidepressants and anticonvulsants to provide adequate pain relief. Traditional pain relievers, such as NSAIDs or opioids, often are not useful. Central pain syndrome can lead to a chronic and disabling illness that causes a significant impact on a patient's quality of life. Reports exist of widespread generalized pain in up to one-fifth of the adult patient population.[2]


Central pain is often referred to as neuropathic pain, which has localized to the central nervous system.[1] Historically, central pain syndrome was a psychiatric diagnosis seen following a traumatic brain injury or thought to be a diagnosis of exclusion. The theory behind centralized pain was that it was a dysfunction of the nervous system rather than an adaptive change seen with musculoskeletal (nociceptive) pain.[3] For example, it is beneficial to withdraw one's hand away from an open flame. The purpose of pain is protection - to limit harm. Central pain was thought to be the feeling of pain without the fire. Not only is it not protective, but it is also actually maladaptive.

As multiple systemic syndromes overlap, sensory amplification and pain increase. An estimated 2% to 4% of the population suffers from fibromyalgia, 1% from chronic fatigue, and 4% from somatoform disorders. There is considerable overlap between regional pain syndromes such as these and psychiatric disorders.  

Central pain syndrome is a type of neuropathic pain in the central nervous system. It can occur in patients following a stroke or in patients who have multiple sclerosis. It is seen in various chronic rheumatological and musculoskeletal disorders as well. When any acute pain becomes chronic, it can undergo centralization, putting patients at risk for developing central pain syndrome.

Furthermore, though patients with chronic pain syndrome consider their pain to be peripheral in origin, in reality, it is mostly centralized. The neural signal has become amplified, leading to hyperalgesia and allodynia. When a patient suffers from a peripheral pain state with nociceptive pain, such as rheumatoid arthritis, this pain becomes centralized with time. The patient's pain is then considered to be in a mixed state.[1][2] Chronic back pain is such an example of peripheral pain becoming centralized.[4][5] Risk factors for fibromyalgia parallel the risk factors for central pain syndrome. These risk factors include trauma, infection, chronic stress, obesity, and depression. Centralized sensitization occurs when there is minimal or no nociceptive input. Functional neuroimaging can aid in diagnosis as well. 

In reality, centralized pain is not mutually exclusive to other types of pain. There is an overlap between pain states. Any central pain state can have a component of peripheral pain, such as peripheral neuropathy. Moreover, there is a significant family predisposition for centralized pain syndrome.[6][7] Psychological stressors can also trigger worsening symptoms. In many cases, environmental factors cause a triggering event in patients with genetic susceptibility, leading to widespread, centralized pain.[8][9] Thus environmental stressors require management. Early life trauma, infection, or emotional stress can cause centralized pain in 5% to 10% of patients.[10][11]

There is an estimated 50% environmental component to developing centralized pain and a 50% genetic component. First-degree relatives are at eight times greater risk of developing widespread pain compared to the average population. However, there is no significant difference based upon the sex of the patient or family member. The genetic association is more prominent in families with a history of mood disorders.[7][12][13] There may be a genetic component to the widespread pain, but there has not been a single genetic polymorphism identified.[14]


Chronic widespread pain seen in centralized pain occurs between 10 to 40 percent of patients with rheumatoid arthritis, psoriatic arthritis, osteoarthritis, spondyloarthritis, and lupus. Centralized pain occurs between five and fifteen percent of the general population, most of whom have fibromyalgia.[2][1] The criteria for fibromyalgia diagnosis overlap considerably with centralized pain, with patients with fibromyalgia who report severe fatigue at a fivefold increase for widespread pain.[15] The prevalence of the overlap of central pain syndrome and knee osteoarthritis is between 10 and 15 percent. The prevalence increases if knee pain was bilateral compared to only a single knee.[16][17][18]

The reported incidence of centralized pain in rheumatoid arthritis is estimated to be between 13 to 40 percent. One concern with this patient population is overtreating their rheumatoid arthritis because of increased symptoms, which are actually due to centralized pain. Inflammatory markers are lower in patients with comorbid fibromyalgia and rheumatoid arthritis, while simultaneously, they reported decreased quality of life compared to those with rheumatoid arthritis alone.[19][20]

Centralized pain syndrome appears in 10 to 30 percent of patients with spondyloarthritis. Separately, 13 to 20 percent of patients with ankylosing spondylitis meet the criteria for fibromyalgia.[21][22][23] Patients with widespread pain are much more likely to have clinically significant fatigue with a comorbid mood disorder with moderate to severe symptoms. In one study, centralized pain was present in 53 percent of patients with psoriatic arthritis but only five percent of the average population.[24] Patients with centralized pain were also more likely to be lost to follow up after initiating treatment. Separately, centralized pain presents in 20 to 40 percent of patients with lupus or Sjogren syndrome. Furthermore, symptoms were more prevalent as chronic diseases progressed and in patients with comorbid depression.[25][26] Over a third of women with chronic back pain suffer from centralized pain. The daily impact of central pain is significant in patients with chronic back pain, including severe limitations in their activity level. Given the significant prevalence of widespread, centralized pain in women with chronic low back pain, it is reasonable to consider central pain syndrome as part of the differential diagnosis in this patient population.[27]

History and Physical

The diagnosis of centralized pain is symptoms of pain lasting at least three months, with widespread allodynia or hyperalgesia, without any apparent cause of pain. Centralized pain can be either generalized or in multiple locations in the body. Upon normal pressure of palpation, if the pain is reproducible, there is likely hyperalgesia or allodynia secondary to mechanical pressure over a joint or muscle.[28] Centralized pain is associated with mood changes, fatigue, cognitive disturbances, sleep changes, pain catastrophizing, and symptoms of neuropathic pain (burning, numbness, tingling, and paraesthesias). Generally, patients with central pain syndrome will have multifocal pain, memory complaints, and often comorbid major depressive disorder or generalized anxiety disorder.[2] Noxious stimuli, such as extremes of temperature or loud sounds.[28] Providing the patient with a drawing of the human body can help document areas of pain.[15]

The history of the pain should include its onset, description, location, radiation, quality, and severity. Also, the mechanism of injury, if applicable, and factors contributing to its relief or worsening, its frequency, and whether there is any breakthrough pain. Furthermore, associated symptoms should be addressed, such as muscle spasms or aches, temperature changes, restrictions to range of motion, morning stiffness, weakness, changes in muscle strength, changes in sensation, and hair, skin, or nail changes.

Separately, on the physical exam, a detailed neurologic exam should be done and an examination of the area exhibiting pain. When evaluating for central pain syndrome, a full musculoskeletal exam is recommended. Further evaluation for symmetrical tender points, as seen in fibromyalgia, should also be considered. To be diagnosed with central pain syndrome, pain is often widespread, on the axial skeleton, on both sides of the body, and above and below the diaphragm.[2][15] Document any tenderness over soft tissues or joints. On exam, if there is swelling, structural changes, abnormal neurological findings, or concern for inflamed joints, centralized pain is less likely.


The diagnosis for central pain is mostly clinical, given that the laboratory workup, which includes a CBC, ESR, CRP, TSH, CK, is generally negative.[29] Labs are therefore not indicated unless there is clinical suspicion for their utility. There are also limited genetic biomarkers in the diagnosis of centralized pain.[1] Rheumatologic markers such as RF and ANA are not necessary unless an autoimmune disorder is suspected. 

Screening instruments for central pain are available. These tools included the central sensitization inventory (CSI), as well as the painDETECT measure. These tools can serve to assess neuropathic pain and centralized pain syndromes such as fibromyalgia, respectively.[30][31] It is challenging to differentiate the origin of pain, whether it is central or peripheral. The painDETECT instrument cannot distinguish between peripheral neuropathy secondary to a central or peripheral source.[30]

Furthermore, imaging can help confirm central pain syndrome. MRI and functional neuroimaging (fMRI) have helped shed light on central pain. An fMRI can help distinguish structural and functional brain abnormalities in patients with various chronic pain disorders. Patients with fibromyalgia have demonstrated unique brain patterns on fMRI. It can be a useful tool in diagnosing and predicting patients at risk for developing various pain disorders.[32][33] These abnormal findings on fMRI include decreased brain volume and cortical thickness and an increase in the level of excitatory neurotransmitters.[32]

Furthermore, fMRI is useful in helping to determine the connectivity between multiple regions of the brain. The extent of alteration correlates with the scope of the patient's pain. A functional MRI could be an objective measure of the severity of fibromyalgia.[34] The pain signals seen on fMRI in patients diagnosed with fibromyalgia are different than the average population. Functional MRI is a promising test that may be beneficial in the future to diagnose multiple pain disorders.[35][33]

Increased pain responses have been seen in patients with central pain syndrome on positron emission tomography and electroencephalography.[36][37]

Treatment / Management

Treatment often focuses on treating the underlying chronic disease state associated with centralized pain. Treatment of a comorbid condition associated with centralized pain is beneficial in relieving a patient's pain.[38] For example, in knee osteoarthritis, neuroimaging changes associated with central pain syndromes improved with joint replacement. Central pain disorders often respond to neuromodulators, antiepileptics, or antidepressants rather than peripheral pain pharmacological agents such as NSAIDs or opioid analgesics.[1][2] 

Motor cortex stimulation (MCS) and deep brain stimulation (DBS) are effective treatment modalities for patients with refractory pain, centralized pain, and peripheral neuropathy.[39]

Nonpharmacological interventions are also primary treatment for patients with centralized pain, including cognitive-behavioral therapy. A holistic approach is necessary for the treatment of centralized pain. There often can be a structural, immunologic, or inflammatory component to the underlying disease.

Pharmacological therapies recommended for central pain syndrome include TCA's, SNRIs, and anticonvulsants. There is strong evidence for the use of TCA’s such as amitriptyline, SNRIs such as duloxetine or venlafaxine, as well as the anticonvulsants pregabalin and gabapentin. There is moderate evidence for the use of tramadol or an SSRI and weak evidence for using S-adenosyl-L-methionine (SAMe). 

Differential Diagnosis

Central pain presents in many chronic pain disorders, including fibromyalgia, interstitial cystitis, temporomandibular disease, and irritable bowel syndrome. The differential diagnosis for central pain syndrome includes rheumatologic disorders such as polymyalgia rheumatica (PMR), myopathy or myositis, rheumatoid arthritis, psoriatic arthritis, or lupus.

Furthermore, centralized pain often accompanies chronic back and neck pain. It also has correlations with trauma, carpal tunnel syndrome, complex regional pain syndrome, lateral epicondylitis, osteoarthritis, and joint hypermobility syndrome. Centralized pain following a stroke or sequella of a neurological disorder such as multiple sclerosis is also part of the differential.[40][41] A thalamic stroke is also associated with a specific form of centralized pain syndrome. Lastly, mood disorders such as major depressive disorder or generalized anxiety disorder are related to centralized pain.


Prognosis is better in patients when the underlying disease state, which initially caused the pain, can be cured, corrected, or managed, as in a shoulder replacement in osteoarthritis. Patients with osteoarthritis and centralized pain report pain reduction with pharmacological therapy aimed at osteoarthritis and an increase in adverse pain outcomes following joint replacement surgery.[42] 

Prognostically, when osteoarthritis is comorbid with central pain syndrome, the severity of patients' pain does not correlate with the radiographic severity of osteoarthritis. Furthermore, these patients with radiological evidence of osteoarthritis in a single joint were at increased risk of having multiple painful joints.[16] Furthermore, this comorbid population has a higher degree of synovitis and effusion in knee osteoarthritis.[18]

Central sensitization also plays a role in inflammatory arthritis. It occurs in a significant subset of the patient population.[19] Furthermore, patients with rheumatoid arthritis and comorbid fibromyalgia have worse reported pain, poorer mental health, take more medications for pain, including prednisone, while simultaneously have lower levels of inflammatory markers.[43][20][44][20] Patients with inflammatory arthritis and central pain syndrome also have poorer outcomes.[45] Patients with centralized pain and comorbid rheumatoid arthritis suffer from hyperalgesia at nonarticular sites in addition to articular surfaces.[46][22]


The impact of central pain disorder affects multiple conditions. 

  • In rheumatoid arthritis, central pain is associated with neuropathic symptoms, increase pain scores without changes to inflammatory markers, increased adverse outcomes, as well as reduced remission rates.
  • Central sensitization is associated with the increased use of opioids, as well as increased pain severity in patients with osteoarthritis and is related to poorer patient outcomes.
  • Patients with bilateral knee pain are at increased risk for joint pain in areas other than the knees at a one-year follow-up.[16][38]
  • For spondyloarthritis, central sensitization correlates with worse outcomes and disease scores, as well as poorer results in treatment.
  • In chronic back pain, central pain syndrome causes more significant pain and mood changes, as well as increased adverse outcomes. In joint hypermobility syndrome it correlates with increased pain severity and poorer patient outcomes.
  • For chronic whiplash injuries, centralized pain correlates with cognitive disturbances, increased pain, and poorer outcomes. 
  • In lupus, centralized pain carries associations with more significant sleep disturbances and mood changes and worse outcomes.
  • In patients with carpal tunnel syndrome, central pain syndrome is associated with poorer surgical outcomes, while in lateral epicondylitis, it is associated with more severe pain, increased duration of pain, and greater risk of failed treatment responses.
  • Preoperative increases in fibromyalgia pain scores correlated with the administration of more postoperative morphine equivalents and a reduced response of NSAIDs.[47][38]

Deterrence and Patient Education

  • Centralized pain occurs when the central nervous system becomes sensitized to pain, leading to a lower pain threshold.
  • The prevalence of widespread pain or central pain is relatively common. It is present in up to 20% of patients with chronic pain from any cause.
  • Common symptoms of centralized pain are: pain from nonpainful contact or pressure (allodynia) and increased pain from painful stimuli (hyperalgesia).
  • Patients suffering from chronic rheumatological and musculoskeletal conditions for at least three months are at increased risk of developing central pain syndrome.
  • There is both an environmental and genetic component to developing central pain syndrome.
  • A patient can both have a chronic disease causing pain (peripheral pain) and centralized pain (central pain syndrome), and this risk increases over time.
  • Functional MRI may be a useful diagnostic test in the diagnosis of various pain disorders.
  • Centralized pain can significantly and negatively impact multiple chronic disease states, including osteoarthritis and rheumatoid arthritis.
  • A pain medicine specialist alongside a primary care physician may be necessary to treat central pain syndrome. 
  • Treatment of a comorbid disease alongside centralized pain can improve a patient's pain.
  • First-line treatments for centralized pain include antidepressants and anticonvulsants.

Enhancing Healthcare Team Outcomes

Managing central pain syndrome requires an interprofessional team that includes a pharmacist, nursing staff, and several physicians in different specialties. The healthcare team consists of a primary care physician, a pain medicine specialist, and possibly a specialist for the primary source of the patient's pain, such as a rheumatologist or neurologist, and a pharmacist should also consult on these cases. Without proper management, the morbidity from central pain syndrome is high. Centralized pain requires proper identification to receive appropriate treatment. It requires a different treatment strategy compared with peripheral or mechanical pain:

  • Ordering a CBC, ESR, CRP, and CK is often part of the initial workup in central pain disorder.
  • Monitor the patient for signs and symptoms of centralized pain such as allodynia or hyperalgesia.
  • Pain typically lasts for greater than three months. There is possibly a genetic component to the pain, as well as an environmental component.
  • Consult with the pharmacist about the use of anticonvulsants and or antidepressants for chronic pain.
  • Consult with a pain medicine specialist and the primary care physician for further management, which may include neuromodulation.
  • Consult with the radiologist about imaging tests such as a functional MRI, which can aid in diagnosis.
  • Consult with the rheumatologist or neurologist to treat the underlying inflammatory or neurological disorder, respectively.

The management of central pain disorder requires a full complement of healthcare professionals. Prevention of the development of centralized pain is a worthy goal, given the significant morbidity associated with the diagnosis. The long-term improvement of the symptoms of centralized pain remains guarded. Nursing staff can monitor the patient, serve as a liaison between disciplines, and answer patient questions while charting and informing the team of their observations. Treatment requires meaningful patient education and patience on the part of both healthcare professionals and patients. Complete eliminating pain may not be possible, but improving the quality of life for the patients is nearly always achievable. [Level 2] AN interprofessional team approach will optimize the patient outcomes in these cases. [Level 5]

Article Details

Article Author

Alexander Dydyk

Article Editor:

Amy Givler


7/12/2021 8:33:31 PM

PubMed Link:

Central Pain Syndrome



Woolf CJ, Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011 Mar;     [PubMed PMID: 20961685]


McBeth J,Jones K, Epidemiology of chronic musculoskeletal pain. Best practice     [PubMed PMID: 17602991]


Clauw DJ,Hassett AL, The role of centralised pain in osteoarthritis. Clinical and experimental rheumatology. 2017 Sep-Oct;     [PubMed PMID: 28967359]


Mutso AA,Petre B,Huang L,Baliki MN,Torbey S,Herrmann KM,Schnitzer TJ,Apkarian AV, Reorganization of hippocampal functional connectivity with transition to chronic back pain. Journal of neurophysiology. 2014 Mar;     [PubMed PMID: 24335219]


Yu R,Gollub RL,Spaeth R,Napadow V,Wasan A,Kong J, Disrupted functional connectivity of the periaqueductal gray in chronic low back pain. NeuroImage. Clinical. 2014;     [PubMed PMID: 25379421]


Buskila D, Genetics of chronic pain states. Best practice     [PubMed PMID: 17602998]


Arnold LM,Hudson JI,Hess EV,Ware AE,Fritz DA,Auchenbach MB,Starck LO,Keck PE Jr, Family study of fibromyalgia. Arthritis and rheumatism. 2004 Mar;     [PubMed PMID: 15022338]


Williams DA,Clauw DJ, Understanding fibromyalgia: lessons from the broader pain research community. The journal of pain : official journal of the American Pain Society. 2009 Aug;     [PubMed PMID: 19638325]


Clauw DJ,Chrousos GP, Chronic pain and fatigue syndromes: overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation. 1997 May-Jun;     [PubMed PMID: 9500148]


Clauw DJ,Schmidt M,Radulovic D,Singer A,Katz P,Bresette J, The relationship between fibromyalgia and interstitial cystitis. Journal of psychiatric research. 1997 Jan-Feb;     [PubMed PMID: 9201654]


McLean SA,Clauw DJ, Predicting chronic symptoms after an acute     [PubMed PMID: 15325010]


Kato K,Sullivan PF,Evengård B,Pedersen NL, Importance of genetic influences on chronic widespread pain. Arthritis and rheumatism. 2006 May;     [PubMed PMID: 16646040]


Buskila D,Sarzi-Puttini P, Biology and therapy of fibromyalgia. Genetic aspects of fibromyalgia syndrome. Arthritis research     [PubMed PMID: 16887010]


Arnold LM,Fan J,Russell IJ,Yunus MB,Khan MA,Kushner I,Olson JM,Iyengar SK, The fibromyalgia family study: a genome-wide linkage scan study. Arthritis and rheumatism. 2013 Apr;     [PubMed PMID: 23280346]


Dean LE,Arnold L,Crofford L,Bennett R,Goldenberg D,Fitzcharles MA,Paiva ES,Staud R,Clauw D,Sarzi-Puttini P,Jones GT,Ayorinde A,Flüß E,Beasley M,Macfarlane GJ, Impact of Moving From a Widespread to Multisite Pain Definition on Other Fibromyalgia Symptoms. Arthritis care     [PubMed PMID: 28182834]


Felson DT,Niu J,Quinn EK,Neogi T,Lewis CL,Lewis CE,Frey Law L,McCulloch C,Nevitt M,LaValley M, Multiple Nonspecific Sites of Joint Pain Outside the Knees Develop in Persons With Knee Pain. Arthritis     [PubMed PMID: 27589036]


Neogi T,Frey-Law L,Scholz J,Niu J,Arendt-Nielsen L,Woolf C,Nevitt M,Bradley L,Felson DT, Sensitivity and sensitisation in relation to pain severity in knee osteoarthritis: trait or state? Annals of the rheumatic diseases. 2015 Apr;     [PubMed PMID: 24351516]


Neogi T,Guermazi A,Roemer F,Nevitt MC,Scholz J,Arendt-Nielsen L,Woolf C,Niu J,Bradley LA,Quinn E,Law LF, Association of Joint Inflammation With Pain Sensitization in Knee Osteoarthritis: The Multicenter Osteoarthritis Study. Arthritis     [PubMed PMID: 26554395]


Pollard LC,Kingsley GH,Choy EH,Scott DL, Fibromyalgic rheumatoid arthritis and disease assessment. Rheumatology (Oxford, England). 2010 May;     [PubMed PMID: 20100795]


Andersson ML,Svensson B,Bergman S, Chronic widespread pain in patients with rheumatoid arthritis and the relation between pain and disease activity measures over the first 5 years. The Journal of rheumatology. 2013 Dec;     [PubMed PMID: 24187108]


Baraliakos X,Regel A,Kiltz U,Menne HJ,Dybowski F,Igelmann M,Kalthoff L,Krause D,Saracbasi-Zender E,Schmitz-Bortz E,Braun J, Patients with fibromyalgia rarely fulfil classification criteria for axial spondyloarthritis. Rheumatology (Oxford, England). 2018 Sep 1;     [PubMed PMID: 28968885]


Duffield SJ,Miller N,Zhao S,Goodson NJ, Concomitant fibromyalgia complicating chronic inflammatory arthritis: a systematic review and meta-analysis. Rheumatology (Oxford, England). 2018 Aug 1;     [PubMed PMID: 29788461]


Bello N,Etcheto A,Béal C,Dougados M,Moltó A, Evaluation of the impact of fibromyalgia in disease activity and treatment effect in spondyloarthritis. Arthritis research     [PubMed PMID: 26860612]


Magrey MN,Antonelli M,James N,Khan MA, High frequency of fibromyalgia in patients with psoriatic arthritis: a pilot study. Arthritis. 2013;     [PubMed PMID: 23476767]


Torrente-Segarra V,Salman-Monte TC,Rúa-Figueroa Í,Pérez-Vicente S,López-Longo FJ,Galindo-Izquierdo M,Calvo-Alén J,Olivé-Marqués A,Ibañez-Ruán J,Horcada L,Sánchez-Atrio A,Montilla C,Rodríguez-Gómez M,Díez-Álvarez E,Martinez-Taboada V,Andreu JL,Fernández-Berrizbeitia O,Hernández-Beriain JA,Gantes M,Hernández-Cruz B,Pecondón-Español Á,Marras C,Bonilla G,Pego-Reigosa JM, Fibromyalgia prevalence and related factors in a large registry of patients with systemic lupus erythematosus. Clinical and experimental rheumatology. 2016 Mar-Apr;     [PubMed PMID: 26575317]


Wolfe F,Petri M,Alarcón GS,Goldman J,Chakravarty EF,Katz RS,Karlson EW, Fibromyalgia, systemic lupus erythematosus (SLE), and evaluation of SLE activity. The Journal of rheumatology. 2009 Jan;     [PubMed PMID: 19004039]


Nordeman L,Gunnarsson R,Mannerkorpi K, Prevalence and characteristics of widespread pain in female primary health care patients with chronic low back pain. The Clinical journal of pain. 2012 Jan;     [PubMed PMID: 21677567]


Staud R,Robinson ME,Price DD, Temporal summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patients. The journal of pain : official journal of the American Pain Society. 2007 Nov;     [PubMed PMID: 17681887]


Lesuis N,van Vliet J,Boers N,den Broeder N,Cats H,Hulscher ME,Verrips A,den Broeder AA, The value of routine creatine kinase and thyroid stimulating hormone testing in patients with suspected fibromyalgia: a cross-sectional study. Rheumatology (Oxford, England). 2016 Jul;     [PubMed PMID: 27032423]


Timmerman H,Wolff AP,Bronkhorst EM,Wilder-Smith OHG,Schenkels MJ,van Dasselaar NT,Huygen FJPM,Steegers MAH,Vissers KCP, Avoiding Catch-22: validating the PainDETECT in a in a population of patients with chronic pain. BMC neurology. 2018 Jun 29;     [PubMed PMID: 29958535]


Neblett R,Cohen H,Choi Y,Hartzell MM,Williams M,Mayer TG,Gatchel RJ, The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample. The journal of pain : official journal of the American Pain Society. 2013 May;     [PubMed PMID: 23490634]


Jensen KB,Srinivasan P,Spaeth R,Tan Y,Kosek E,Petzke F,Carville S,Fransson P,Marcus H,Williams SC,Choy E,Vitton O,Gracely R,Ingvar M,Kong J, Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain. Arthritis and rheumatism. 2013 Dec;     [PubMed PMID: 23982850]


Wager TD,Atlas LY,Lindquist MA,Roy M,Woo CW,Kross E, An fMRI-based neurologic signature of physical pain. The New England journal of medicine. 2013 Apr 11;     [PubMed PMID: 23574118]


Napadow V,Kim J,Clauw DJ,Harris RE, Decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia. Arthritis and rheumatism. 2012 Jul;     [PubMed PMID: 22294427]


López-Solà M,Woo CW,Pujol J,Deus J,Harrison BJ,Monfort J,Wager TD, Towards a neurophysiological signature for fibromyalgia. Pain. 2017 Jan;     [PubMed PMID: 27583567]


Usui C,Soma T,Hatta K,Aratani S,Fujita H,Nishioka K,Machida Y,Kuroiwa Y,Nakajima T,Nishioka K, A study of brain metabolism in fibromyalgia by positron emission tomography. Progress in neuro-psychopharmacology     [PubMed PMID: 28153806]


Lee U,Kim M,Lee K,Kaplan CM,Clauw DJ,Kim S,Mashour GA,Harris RE, Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain. Scientific reports. 2018 Jan 10;     [PubMed PMID: 29321621]


Brummett CM,Urquhart AG,Hassett AL,Tsodikov A,Hallstrom BR,Wood NI,Williams DA,Clauw DJ, Characteristics of fibromyalgia independently predict poorer long-term analgesic outcomes following total knee and hip arthroplasty. Arthritis     [PubMed PMID: 25772388]


Moore NZ,Lempka SF,Machado A, Central neuromodulation for refractory pain. Neurosurgery clinics of North America. 2014 Jan;     [PubMed PMID: 24262901]


Report of the American College of Rheumatology Pain Management Task Force. Arthritis care     [PubMed PMID: 20461782]


Borenstein DG,Hassett AL,Pisetsky D, Pain management in rheumatology research, training, and practice. Clinical and experimental rheumatology. 2017 Sep-Oct;     [PubMed PMID: 28967362]


Finan PH,Buenaver LF,Bounds SC,Hussain S,Park RJ,Haque UJ,Campbell CM,Haythornthwaite JA,Edwards RR,Smith MT, Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization. Arthritis and rheumatism. 2013 Feb;     [PubMed PMID: 22961435]


Lee YC,Lu B,Boire G,Haraoui BP,Hitchon CA,Pope JE,Thorne JC,Keystone EC,Solomon DH,Bykerk VP, Incidence and predictors of secondary fibromyalgia in an early arthritis cohort. Annals of the rheumatic diseases. 2013 Jun;     [PubMed PMID: 22791744]


Chakr RMDS,Brenol C,Ranzolin A,Bernardes A,Dalosto AP,Ferrari G,Scalco S,Olszewski V,Kohem C,Monticielo O,Brenol JCT,Xavier RM, Rheumatoid arthritis seems to have DMARD treatment decision influenced by fibromyalgia. Revista brasileira de reumatologia. 2017 Sep - Oct;     [PubMed PMID: 29037312]


Koop SM,ten Klooster PM,Vonkeman HE,Steunebrink LM,van de Laar MA, Neuropathic-like pain features and cross-sectional associations in rheumatoid arthritis. Arthritis research     [PubMed PMID: 26335941]


Meeus M,Vervisch S,De Clerck LS,Moorkens G,Hans G,Nijs J, Central sensitization in patients with rheumatoid arthritis: a systematic literature review. Seminars in arthritis and rheumatism. 2012 Feb;     [PubMed PMID: 22035625]


Edwards RR,Dolman AJ,Martel MO,Finan PH,Lazaridou A,Cornelius M,Wasan AD, Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis. BMC musculoskeletal disorders. 2016 Jul 13;     [PubMed PMID: 27412526]