740076

research-article2017
TAB0010.1177/1759720X17740076Therapeutic Advances in Musculoskeletal DiseaseD Kumbhare, S Ahmed

Therapeutic Advances in Musculoskeletal Disease Review

A narrative review on the difficulties

Ther Adv Musculoskel Dis

2018, Vol. 10(1) 13­–26

associated with fibromyalgia diagnosis DOI: 10.1177/

https://doi.org/10.1177/1759720X17740076
https://doi.org/10.1177/1759720X17740076
1759720X17740076

© The Author(s), 2017.

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Abstract:  Fibromyalgia presents a clinical enigma as its pathophysiology is not well

understood and its symptoms are nonspecific and overlap with many disorders, making its
diagnosis a challenge for clinicians and researchers. Efforts have been made to develop
a set of diagnostic criteria for this disorder. However, these criteria rely heavily on expert
clinician opinion and produce a large heterogeneity within the diagnosed population. With
no present specific technique reflecting the underlying pathophysiology of fibromyalgia, a
definitive diagnosis of fibromyalgia remains elusive. This review discusses some problems and
challenges associated with fibromyalgia diagnosis and presents some novel findings on the
pathophysiological nature of fibromyalgia.

Keywords:  Fibromyalgia; diagnostic criteria

Received: 17 July 2017; accepted in revised form: 11 October 2017

Introduction criteria were revisited in 2010 to account for Correspondence to:

Fibromyalgia presents a clinical enigma. Its
pathophysiology is not well understood and its
symptoms are nonspecific and overlap with many
disorders, making its diagnosis a challenge for cli-
nicians and researchers. Efforts have been made
to develop a set of diagnostic criteria for this dis-
order. Classification criteria were developed in
1990 and diagnostic criteria were implemented in
2010 by the American College of Rheumatology
(ACR). The 2010 criteria were modified in 2011
and further modifications to the criteria were
introduced in 2016,1–4 these are currently the
most accepted methods of fibromyalgia diagnosis.
These criteria rely heavily on expert clinician
opinion and are not definitive diagnostic tests,
therefore they produce large heterogeneity within
the diagnosed population. Additionally, many
physicians are not compliant with the diagnostic
criteria and do they do not have a comprehensive
understanding of the disorder.5–8 They rely on
their clinical acumen and judgment for diagnosis,
introducing additional variability into the diag-
nosed population.
The 1990 ACR diagnostic criteria suggest that
widespread pain is the main classifying and clini-
cal characteristic of fibromyalgia.1 The 1990
Dinesh Kumbhare
patients who present less muscle tenderness and Division of Physical
more secondary symptoms, in addition to address- Medicine and
Rehabilitation, Department
ing poor physician use of the tender point count. of Medicine, Toronto
The 2010 criteria introduced a new group of Rehabilitation Institute,
550 University Avenue,
patients who present with higher severity of sec- Toronto, ONT, Canada
ondary symptoms such as depression, poor sleep, M5G 2A2
dinesh.kumbhare@uhn.ca
cognitive symptoms, and somatic symptoms with Sara Ahmed
a minimum of three tender regions.2,4 The 2016 Faculty of Science,
McMaster University,
revision necessitated a minimum of four tender Hamilton, ON, Canada
regions, one in each of four quadrants in the Scott Watter
body, with a high symptom severity score (>9) Department of Psychology,
McMaster University,
for a diagnosis of fibromyalgia. These changes Hamilton, ON, Canada
introduce more heterogeneity into the diagnosis
of patients with fibromyalgia as some may present
with high affective distress and little muscle pain,
and others may present with high levels of muscle
pain and little affective and sleep distress.
Therefore, a substantial barrier for fibromyalgia
diagnosis is the lack of specificity of its diagnostic
signs and symptoms. The specific features of the
diagnostic criteria for fibromyalgia are themselves
common across a wide range of conditions,
beyond even immediate differential diagnoses for
fibromyalgia. Most patients presenting with one
or more of muscle aches and pain, fatigue, poor
sleep and mild cognitive symptoms still may not
have a formal diagnosis of fibromyalgia. It is also

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 Therapeutic Advances in Musculoskeletal Disease 10(1)
Figure 1.  Factors contributing to diagnostic
heterogeneity in clinical groups.
possible that the current fibromyalgia population
is composed of patients who may present primar-
ily with depression, a sleep disorder, a cognitive
affective disorder or a somatic disorder along with
a limited amount of muscle aches and pain.2–4
Symptoms such as pain, fatigue, sleep distur-
bances, cognitive difficulties and depression are
nonspecific and can also be caused by different
pathophysiological mechanisms.
Current literature shows that the tender point
count criterion has been shown to poorly differen-
tiate between fibromyalgia and other pain disor-
ders such as myofascial pain syndrome.9,10 Gerwin
and colleagues11,12 also report the clinical presence
of tender points in 79% of patients with myofas-
cial pain syndrome and an overlap with fibromyal-
gia of approximately 40%. Additionally, the tender
point count is typically higher in women relative to
men, therefore more women are likely to be diag-
nosed with fibromyalgia.13,14 Jones and colleagues15
found that more women were diagnosed with
fibromyalgia relative to men using the 1990, 2010
and modified 2010 criteria. However, the preva-
lence of women with fibromyalgia relative to men
using the 1990 criteria, which utilizes only the ten-
der point count, was 13.7 fold and was lower for
the other criteria. Several studies have delineated
clinical subgroups among patients with fibromyal-
gia diagnosed with the 1990 criteria, which is con-
sidered the most specific definition of fibromyalgia,
14 journals.sagepub.com/home/tab
02_TAB740076.indd 14
suggesting that the 1990 criteria diagnose a het-
erogeneous spectrum of patients.16–18 The severity
of the variables assessed in the subgroups ranged
from experiencing psychological wellbeing, low
pain and little disability to displaying physiological
(neuroendocrine, immune, metabolic) dysregula-
tion, high anxiety, as well as severe pain and disa-
bility. These presentations could theoretically
have been the result of various pathophysiological
mechanisms. Therefore, the 2010, 2011 and 2016
criteria likely diagnose a more heterogeneous
group of individuals relative to the 1990
criteria.16–18
Methodological problems associated with
the accepted classification and diagnostic
criteria
There are some methodological problems associ-
ated with the creation of the 1990 classification
criteria and subsequently the 2010, 2011 and
2016 criteria that may lead to the diagnosis of a
heterogeneous group of patients. Figure 1 high-
lights the factors that are contributing to the diag-
nostic heterogeneity.
The 1990 classification criteria were developed
through consensus from fibromyalgia experts
using clinical observations and assessments.1
Criteria developed through expert consensus
increases the chances for misdiagnosis because
they are limited to information available to the
expert at that time, which may not be compre-
hensive, and is biased by their internal concept of
the disorder which is dependent on their clinical
experience.19 These types of criteria also vary
across time and countries, where different repre-
sentations of the same condition are accepted.19
Therefore, the sensitivity of 88.4% and specificity
of 81.1% reported for the 1990 criteria may not
have been accurate. The 2010 criteria were devel-
oped using the 1990 criteria as the reference
standard.2 Since the 1990 criteria are not a per-
fect diagnostic tool, the chance of error when
developing the 2010 criteria increased. No statis-
tical adjustments were used to determine accu-
racy rates reflective of the variability in physician
and assessor judgments for both the 1990 and
2010 criteria. The 2011 modification used a dif-
ferent reference standard than the previous crite-
ria, the National Data Bank of Rheumatic
Diseases, in which the fibromyalgia population
was determined by many different clinicians with
undefined diagnostic methods. This further
impacts the diagnostic accuracy of these criteria
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 D Kumbhare, S Ahmed et al.

Table 1.  Validity measures for the fibromyalgia American College of Rheumatology (ACR) diagnostic criteria, adapted from Lijmer
and colleagues (1999)20 and Reid and colleagues (1995)21.

Validity of Accomplished Accomplished Accomplished Accomplished Effect on accuracy and

diagnostic criteria by 1990 criteria by 2010 by 2011 by 2016 generalizability
criteria modification criteria
Specify spectrum of Yes Yes Yes NA Limits generalizability of
evaluated patients studied sample to the stated
demographics
Report test Yes Yes Yes Yes Indexes of accuracy provided
indexes for clinical represent the clinical error with
subgroups the subgroup
Avoid verification Yes Yes Yes NA Distorts indexes of accuracy
bias
Provide numerical No No No No Sensitivity and specificity values
precision for are numerically unstable with
indexes few or nonrepresentative
patients
Specify test No No No No Limits the capability for the
reproducibility criteria to diagnose outside of
the experimental setting
Avoided different No Yes No No Adds variability to reported
reference tests indexes
Avoided partial Yes Yes Yes NA Adds variability to reported
verification indexes
Blinded study Yes Yes NA NA Prevents bias when determining
whether index or reference tests
are positive
Consecutive Yes Yes Yes NA If participants are not enrolled
enrolment of randomly or in a consecutive
patients manner then there is a biased
sample
Prospective No No No NA Overestimation of diagnostic
accuracy if test is evaluated in a
group of patients already known
to have the disease
Description of index Yes Yes Yes Yes Description of tests should be
test described with sufficient detail to
allow for replication, validation,
and generalization
Description of No Yes No Yes Description of tests should be
reference test described with sufficient detail to
allow for replication, validation,
and generalization
NA, not applicable.

relative to the 2010 criteria. The 2016 criteria
were an improvement of the 2010/2011 criteria,
as they addressed shortcomings of the 2010/2011
criteria when validated relative to the 1990 crite-
ria and clinical diagnosis. They are however still
limited by the methodological shortcomings of
the previous criteria. Table 1 contains methodo-
logical measures that should be comprehensively
evaluated when developing a diagnostic method,
and their application during the creation of the

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 Therapeutic Advances in Musculoskeletal Disease 10(1)
1990 classification criteria, 2010, 2011 and 2016
diagnostic criteria based on the reports of Wolfe
and colleagues.1,2
Wolfe and colleagues4 reviewed studies that vali-
dated the 2010 and 2011 criteria against the 1990
criteria. They found several studies that accom-
plished this. Bidari and colleagues22 validated the
2010 criteria against the 1990 criteria by using
dolorimetry to characterize tender points. They
sampled 168 patients with fibromyalgia and 100
controls in Iran. They found that the 2010 crite-
ria had 79.1% accuracy when using the 1990 cri-
teria as the gold standard. Carrillo-de-la-Peña
and colleagues23 validated the Spanish version of
the 2010 criteria against the 1990 criteria. They
recruited 80 patients with fibromyalgia and 59
healthy control Spanish participants. They used
algometry to identify tender points. They found
an inter-criteria agreement of 0.73 between the
2010 and 1990 criteria. Usui and colleagues24
assessed the validity of the Japanese version of the
2010 criteria relative to the 1990 criteria. They
recruited 94 patients with 1990 defined fibromy-
algia and 43 controls from Japan. They found a
sensitivity of 82% when comparing the 2010 cri-
teria with the 1990 criteria. There is a general
decrease in accuracy measures when comparing
the 2010/2011 criteria with the 1990 criteria.4
The current challenge facing researchers and cli-
nicians is to identify a diagnostic marker indica-
tive of a causal mechanism associated with
fibromyalgia to increase the accuracy of diagno-
sis. Current research suggests that central sensiti-
zation is a primary candidate representative of the
pathophysiology underlying fibromyalgia.25,26
The current criteria were not constructed to be
specific to people with central sensitization but
rather individuals with a cluster of symptoms that
expert panels of clinicians have defined as fibro-
myalgia. The criteria likely diagnose a consistent
spectrum of patients; however, they may not cap-
ture the true presence of fibromyalgia. The spe-
cific mechanism responsible for the sensitization
associated with fibromyalgia development should
be elucidated since central sensitization has mul-
tiple etiologies (e.g. bacterial infection, inflamma-
tion, etc.).27,28 This should allow for the separation
of the overall population based upon the underly-
ing mechanism into specific clinical groups each
with a unique underlying pathology and a consist-
ent set of symptoms. The following section pre-
sents findings on potential pathophysiological
indicators of fibromyalgia.
16 journals.sagepub.com/home/tab
02_TAB740076.indd 16
Findings on pathophysiological
perturbations in fibromyalgia
Research elucidating the pathophysiology of
fibromyalgia provides some promising avenues
for novel diagnostic markers. There is a growing
body of evidence suggesting links between chronic
pain and central sensitization, including lower
pain thresholds and hyperalgesia.25,26 Widespread
hyperalgesia differentiates fibromyalgia from
other states of central sensitization, however it
does not yet have the capacity to differentiate it
from other similarly presenting disorders with or
without the presence of central sensitization, such
as myofascial pain syndrome.26,29
Several biological mechanisms have been impli-
cated in the development of the sensitized state in
fibromyalgia. Biomarkers associated with these
mechanisms are shared between several disorders
and can be used to develop cutoffs specific to
fibromyalgia relative to other conditions. A com-
prehensive systematic search of Medline, Central
(including Medline ePub Ahead of Print,
In-Process, and Other Non-Indexed Citations),
and EMBASE was conducted to determine the
mechanisms that led to or are associated with the
sensitized state in patients diagnosed with the
current definition of fibromyalgia. The complete
search strategy includes a comprehensive list of
subject headings and text words to describe
‘fibromyalgia’ and various classes of biomarkers;
this can be found in Appendix A. Studies assess-
ing the presence of biomarkers (or lack thereof) in
fibromyalgia typically used the 1990 criteria to
diagnose their clinical population. The search
indicated that hypothalamic pituitary axis (HPA)
hormones, immune and inflammatory markers,
neuropeptides and neurohormones, and advanced
brain imaging were the most investigated diag-
nostic markers indicative of central sensitization
and fibromyalgia. Here we present a brief sum-
mary of our literature search findings.
HPA hormone perturbations are present in fibro-
myalgia and other related disorders with suspected
underlying central sensitization such as major
depressive disorder, post-traumatic stress disorder
(PTSD) or chronic fatigue syndrome. The combi-
nation of adrenocorticotropic releasing hormone
(ACTH) and cortisol levels in fibromyalgia pre-
sents a distinct profile capable of differentiating it
from other disorders. There is growing consensus
in the literature that high ACTH levels suggest
hyper responsiveness in pituitary release in
response to corticotropin releasing hormone
26/12/2017 4:00:33 PM

(CRH). This has been confirmed using exogenous
infusions of CRH. Plasma or 24 h urinary cortisol
levels are normal to low in people with fibromyal-
gia, indicating hyporesponsivenes at the adrenal
glands to ACTH.30–37 In depression and PTSD,
cortisol levels are chronically elevated whereas in
chronic fatigue syndrome cortisol and ACTH lev-
els are normal.37–40 Evening cortisol levels have
been shown to be higher than normal in fibromy-
algia and lower than normal in chronic fatigue
syndrome.39,41 These factors provide evidence of
differences in HPA regulation between fibromyal-
gia and other central sensitization disorders.
Total oxidative status and immune responses are
also high in fibromyalgia.42 The presence of
antiserotonin antibodies is more common
between fibromyalgia and chronic fatigue syn-
drome relative to other disorders.43 Polymorphisms
in genes coding for serotonin transporters and
catechol-o-methyl transferase are associated with
high pain sensitivity in fibromyalgia. These find-
ings suggest there may be a neuroimmune basis to
this disorder. A robust effect demonstrated in
several studies suggests that levels of interleukin
(IL)-6, IL-8 and IL-10 are high in fibromyalgia
relative to healthy normal or other pain and cen-
tral sensitivity disorders.44–46 Furthermore, tumor
necrosis factor α has been consistently elevated in
disorders of central sensitization, including fibro-
myalgia.45,47–49 Positive correlations exist between
these inflammatory markers and clinical symp-
tom severity. Zanette and colleagues50 identified a
strong correlation between increased serum
brain-derived neurotrophic factor and S100B
protein levels, which is associated with the coex-
istence of neurological disease and central sensi-
tivity syndrome, with lower pressure pain
thresholds in patients with fibromyalgia. Their
findings provide a significant initial step towards
developing biomarkers diagnostic of fibromyal-
gia, ultimately to create a well defined group and
clinical definition.
Advanced brain imaging in fibromyalgia has dem-
onstrated increases in functional connectivity
between anatomical cortical regions associated
with attention, emotion and somatosensory pro-
cessing, including the anterior cingulate cortex,
anterior prefrontal cortex, parietal cortex, dorso-
lateral prefrontal cortex and the insula.51 Increases
in functional connectivity between these areas is
associated with symptom (pain, depression) sever-
ity and pain duration in fibromyalgia.52 There
have also been studies demonstrating attenuated
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D Kumbhare, S Ahmed et al.
blood flow to brain areas associated with inducing
analgesic effects, and increased activity in the pri-
mary and secondary somatosensory cortices in
people with fibromyalgia.51 This suggests that
their nervous system is compensating for the
increase in nociceptive signals received from the
spinal cord and is being subject to hypermetabolic
states due to large amounts of sustained afferent
input. Increases in the glutamate to glutamine
ratio are positively associated with the degree of
functional connectivity and metabolism in brain
areas implicated in central sensitization and fibro-
myalgia.53,54 Decreases in dopamine binding and
precursor uptake are also associated with the
attentional and pain processing abnormalities
observed in fibromyalgia.55,56
These findings point to a multi axial interaction
between neurological, endocrine and immune
systems that results in the development of central
sensitization in fibromyalgia. We suggest the
development of new diagnostic criteria that are
based upon clinical and central sensitization
attributes that better characterize fibromyalgia.
At present, the application of the diagnostic crite-
ria will result in a heterogeneous group that con-
sists of subgroups.
Discussion
Given these findings, researchers should strive
towards creating subgroups within patients diag-
nosed by the current criteria or those with central
sensitization, using some of the well researched
biomarkers. This should identify distinct underly-
ing pathophysiological mechanisms among the
patients and create novel groups, one of which
should be fibromyalgia. For example, biomarkers
that are common to fibromyalgia and other disor-
ders, such as cortisol, can be used to develop
diagnostic cutoffs that help to create better
boundaries for each condition and thus improve
their distinct definitions. Biomarkers may also be
used to understand whether fibromyalgia is truly
a singular entity or a psychosomatic manifestation
of a spectrum disorder continuous with other psy-
chiatric and pain conditions such as depression,
chronic fatigue syndrome or myofascial pain syn-
drome. A cluster analysis or discriminative func-
tion analysis may be used to create a set of criteria
that diagnose a homogenous group representing
fibromyalgia. Clinical signs and symptoms in
combination with indicators of pathophysiologi-
cal mechanisms known to be associated with
fibromyalgia and overlapping disorders should be
26/12/2017 4:00:33 PM
 Therapeutic Advances in Musculoskeletal Disease 10(1)
included. These analyses may inform which vari-
ables are highly predictive of overlapping disor-
ders and whether there is a boundary that
separates symptomatically overlapping condi-
tions. Following this, the predictive ability of a
biomarker profile that can differentiate fibromyal-
gia from other central sensitization disorders
should be undertaken.
Ideally, selected biomarker panels should be able
to diagnose fibromyalgia during its earlier phases,
during a routine exam or in the presence of ques-
tionable symptoms.57–59 The biomarker panel
profile should indicate the stage or severity of the
disorder, be responsive to clinical change and
thereby allow for earlier intervention and preven-
tion of progression. Ideally, the biomarker panel
should also be responsive to the initiation, con-
tinuation, or cessation of external interventions as
this will indicate the patient’s responsiveness to
these interventions. This should address the limi-
tation presented by the 2010 and subsequent cri-
teria, whereby they measure the severity of a
patient who already has fibromyalgia symptoms
rather than to recognize the presence of the disor-
der at any of its stages.
In addition to these disease-specific attributes,
the ideal biomarker should be acquired easily,
noninvasively and affordably for efficient clinical
application. Other easily measured and validated
clinical features of central sensitization such as
the ‘pinch and roll’ technique, pressure algome-
try, brush allodynia and weighted pinpricks that
provide quantitative measures of pain pressure
thresholds and expansion of the receptive fields
should be investigated for their utility to diagnos-
ing fibromyalgia.2,60,61 Cold detection threshold
as well as dermatographia can also be considered
since they reflect the autonomic properties which
seem to associated with the manifestation of
fibromyalgia.62,63 Finally, the current clinical cri-
teria should be revisited upon the development of
an accurate marker that reflects the pathophysiol-
ogy underlying fibromyalgia. Validation of the
criteria or a subset of the criteria that accurately
capture the newly defined fibromyalgia popula-
tion should be conducted, and they should also
be used to augment and indicate the clinical pres-
ence of fibromyalgia.
Conclusion
A problem underlying the diagnosis and manage-
ment of fibromyalgia, extending to other chronic
pain disorders, is the symptom-specific rather
18 journals.sagepub.com/home/tab
02_TAB740076.indd 18
than a mechanistic approach taken towards its
diagnosis and treatment.64 This method of diag-
nosis results in the presence of different clinical
subgroups presenting different pathophysiologi-
cal mechanisms under a single pain disorder
diagnosis, as is present in fibromyalgia. Many
patients may be receiving treatments that may
not be suitable for their presenting condition.
There is a need for well defined mechanism-
based criteria to describe the specific characteris-
tics of fibromyalgia. This should guide the
development of more accurate diagnostic meth-
ods and effective treatments.
Author’s Note
Dinesh Kumbhare and Sara Ahmed are First
Co-Authors of the article.
Funding
This research received no specific grant from any
funding agency in the public, commercial, or not-
for-profit sectors.
Conflict of interest statement
The authors declare that there is no conflict of
interest.
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J Clin Endocrinol Metab 2001; 86: 1034–1039.
35. Korszun A, Sackett-Lundeen L, Papadopoulos
E, et al. Melatonin levels in women with
fibromyalgia and chronic fatigue syndrome.
J Rheumatol 1999; 26: 2675–2680.
36. Lentjes EG, Griep EN, Boersma JW, et al.
Glucocorticoid receptors, fibromyalgia and low
back pain. Psychoneuroendocrinology 1997; 22:
603–614.
37. Maes M, Lin A, Bonacccorso S, et al. Increased
24-hour urinary cortisol excretion in patients
with post-traumatic stress disorder and patients
with major depression, but not in patients with
fibromyalgia. Acta Psychiatr Scand 1998; 9:
328–335.
38. Bazzichi L, Rossi A, Zirafa C, et al. Thyroid
autoimmunity may represent a predisposition for
the development of fibromyalgia? Rheumatol Int
2012; 32: 335–341.
39. Crofford LJ, Young EA, Engleberg NC, et al.
Basal circadian and pulsatile ACTH and cortisol
secretion in patients with fibromyalgia and/or
chronic fatigue syndrome. Brain Behav Immun
2004; 18: 314–325.
40. Holsboer F, Gerken A, Stalla GK, et al. ACTH,
cortisol, and corticosterone output after ovine
corticotropin-releasing factor challenge during
depression and after recovery. Biol Psychiatry
1985; 20: 276–286.
41. Fatima G, Das SK, Mahdi AA, et al. Circadian
rhythm of serum cortisol in female patients with
fibromyalgia syndrome. Indian J Clin Biochem
2013; 28: 181–184.
42. Bozkurt M, Caglayan M, Oktayoglu P, et al.
Serum prolidase enzyme activity and oxidative
status in patients with fibromyalgia. Redox Rep
2014; 19: 148–153.
43. Klein R and Berg PA. High incidence of
antibodies to 5-hydroxytryptamine, gangliosides
and phospholipids in patients with chronic fatigue
and fibromyalgia syndrome and their relatives:
evidence for a clinical entity of both disorders.
Eur J Med Res 1995; 1: 21–26.
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44. Cordero MD, Díaz-Parrado E, Carrión AM, et al.
Is inflammation a mitochondrial dysfunction-
dependent event in fibromyalgia? Antioxid Redox
Signal 2013; 18: 800–807.
45. Cordero MD, De Miguel M, Fernández
AM, et al. Mitochondrial dysfunction and
mitophagy activation in blood mononuclear
cells of fibromyalgia patients: implications in the
pathogenesis of the disease. Arthritis Res Ther
2010; 12: R17.
46. Miyamae T, Seki M, Naga T, et al. Increased
oxidative stress and coenzyme Q10 deficiency
in juvenile fibromyalgia: amelioration of
hypercholesterolemia and fatigue by ubiquinol-10
supplementation. Redox Rep 2013; 18: 12–19.
47. Bote ME, García JJ, Hinchado MD,
et al. Inflammatory/stress feedback
dysregulation in women with fibromyalgia.
Neuroimmunomodulation 2012; 19: 343–351.
48. Blanco I, Janciauskiene S, Nita I, et al. Low
plasma levels of monocyte chemoattractant
protein-1 (MCP-1), tumor necrosis factor-alpha
(TNFα), and vascular endothelial growth factor
(VEGF) in patients with alpha1-antitrypsin
deficiency-related fibromyalgia. Clin Rheumatol
2010; 29: 189–197.
49. Bazzichi L, Rossi A, Massimetti G, et al. Cytokine
patterns in fibromyalgia and their correlation with
clinical manifestations. Clin Exp Rheumatol 2007;
25: 225–230.
50. Zanette SA, Dussan-Sarria JA, Souza A, et al.
Higher serum S100B and BDNF levels are
correlated with a lower pressure-pain threshold in
fibromyalgia. Mol Pain 2014; 10: 46.
51. Williams DA and Gracely RH. Biology and
therapy of fibromyalgia. Functional magnetic
resonance imaging findings in fibromyalgia.
Arthritis Res Ther 2007; 8: 224.
52. Truini A, Tinelli E, Gerardi MC, et al. Abnormal
resting state functional connectivity of the
periaqueductal grey in patients with fibromyalgia.
Clin Exp Rheumatol 2016; 34(2 Suppl. 96):
129–133.
53. Feraco P, Bacci A, Pedrabissi F, et al. Metabolic
abnormalities in pain-processing regions of patients
with fibromyalgia: a 3T MR spectroscopy study.
AJNR Am J Neuroradiol 2011; 32: 1585–1590.
54. Fayed N, Andres E, Rojas G, et al. Brain
dysfunction in fibromyalgia and somatization
disorder using proton magnetic resonance
spectroscopy: a controlled study. Acta Psychiatr
Scand 2012; 126: 115–125.
55. Potvin S, Larouche A, Normand E, et al. DRD3
Ser9Gly polymorphism is related to thermal pain
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10: 969–975.  
56. Wood PB, Patterson JC, Sunderland JJ, et al.  
Reduced presynaptic dopamine activity in  
fibromyalgia syndrome demonstrated with  
positron emission tomography: a pilot study. J  
Pain 2007; 8: 51–58.  
57. Biomedical FAST. NIH definition of biomarker.  
Clin Pharmacol Ther 2001; 69: 89–95.  
 
58. Coriell Institute for Medical Research.  
Characteristics of the ideal biomarker, https://
 
www.coriell.org/research-services/biomarkers/
characteristics-of-the-ideal-biomarker
 
 
59. NCSS Fact Finding Cardiotoxicity Expert  
Working Group. https://www.fda.gov/ohrms/  
dockets/ac/01/briefing/3798b1_04_HOLT.PPT  
60. Fischer AA. Algometry in diagnosis of  
musculoskeletal pain and evaluation of treatment  
outcome: an update. J Musculoskeletal Pain 1998;  
6: 5–32.
61. King CD, Mano KE, Barnett KA, et al. Pressure  
pain threshold and anxiety in adolescent females  
with and without juvenile fibromyalgia: a pilot  
study. Clin J Pain 2017; 33: 620–626.
62. Borg-Stein J and Simons DG. Myofascial pain.
 
Arch Phys Med Rehabil 2002; 83: S40–S47.
 
63. Maier C, Baron R, Tölle TR, et al. Quantitative  
sensory testing in the German Research Network  
on Neuropathic Pain (DFNS): somatosensory
 
abnormalities in 1236 patients with different
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439–450.  
 
64. Simon LS. Relieving pain in America: a blueprint  
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26: 197–198.
 
 
Appendix A  
Database: Ovid MEDLINE(R) Epub Ahead of  
Print, In-Process & Other Non-Indexed Citations,  
Ovid MEDLINE(R) Daily and Ovid MEDLINE(R)  
<1946 to Present>  
Search Strategy:  
 
  1 Fibromyalgia/ (7608)  
  2 Fibromyalgi*.tw,kw. (8857)  
  3 fibrositis*.tw,kw. (586)  
  4 or/1-3 (10300)  
   5 exp Reactive Oxygen Species/ (160522)  
   6 reactive oxygen spec*.tw,kw. (86480)  
  7 ROS*1.tw,kw. (127059)  
   8 active oxygen*.tw,kw. (2664)  
   9 pro oxidant*.tw,kw. (4490)  
journals.sagepub.com/home/tab 21
02_TAB740076.indd 21
D Kumbhare, S Ahmed et al.
10 prooxidant*.tw,kw. (2705)
11 oxygen radical*.tw,kw. (8512)
12 Hydroxyl Radical*.tw,kw. (15891)
13 hypochlorous acid*.tw,kw. (1866)
14 hypochlorite*.tw,kw. (5723)
15 peroxide*.tw,kw. (62557)
16 singlet oxygen*.tw,kw. (6764)
17 singlet dioxygen*.tw,kw. (19)
18 or/5-17 [ROS terms] (318259)
19 4 and 18 (49)
20 Nerve Growth Factors/ (19795)
21 Nerve Growth Factor/ (6367)
22 ngf.tw,kw. (14151)
23 nerve growth factor*.tw,kw. (17267)
24 neurotrophin*.tw,kw. (10853)
25 neurotrophic protein*.tw,kw. (130)
26 neurotrophic factor*.tw,kw. (23498)
27 neurite outgrowth factor*.tw,kw. (37)
28 neuronotrophic factor*.tw,kw. (153)
29 neuronal growth-associated protein*.
tw,kw. (63)
30 or/20-29 [NGF Terms] (52362)
31 4 and 30 (36)
32 Brain-Derived Neurotrophic Factor/
(12600)
33 brain derived neurotrophic factor*.tw,kw.
(14020)
34 bdnf*1.tw,kw. (15555)
35 or/32-34 [BDNF Terms] (19119)
36 4 and 35 (20)
37 Insulin-Like Growth Factor I/ (31283)
38 insulin like growth factor I.tw,kw. (14082)
39 insulin like growth factor 1.tw,kw. (11139)
40 igf-i.tw,kw. (21983)
41 igf-1.tw,kw. (13669)
42 somatomedin c.tw,kw. (1084)
43 insulin-like somatomedin peptide i.tw,kw. (0)
44 insulin-like somatomedin peptide
1.tw,kw. (0)
45 exp Somatomedins/ (38738)
46 Somatomedin*.tw,kw. (2456)
47 or/37-46 [IGF Terms] (54087)
48 4 and 47 (67)
49 Growth Hormone/ (42705)
50 Human Growth Hormone/ (13200)
51 Somatotropin.rn. (42)
52 Growth Hormone*.tw,kw. (53440)
53 somatotropin*.tw,kw. (4018)
54 somatropin*.tw,kw. (224)
55 GH.tw,kw. (36498)
56 HGH.tw,kw. (4266)
57 RHGH.tw,kw. (1662)
58 “HGH(m)”.tw,kw. (2)
59 “rHGH(m)”.tw,kw. (5)
60 or/49-59 [GH Terms] (79019)
61 4 and 60 (98)
26/12/2017 4:00:34 PM
 Therapeutic Advances in Musculoskeletal Disease 10(1)
  62 Transforming Growth Factor alpha/
(4123)
 63 transforming growth factor alpha.tw,kw.
(4016)
  64 transforming growth factor a.tw,kw. (32)
  65 tgf-alpha.tw,kw. (4097)
  66 tgf-a.tw,kw. (50)
  67 tgfalpha.tw,kw. (821)
  68 tgfa.tw,kw. (276)
  69 (epidermal adj4 transforming growth fac-
tor*).tw,kw. (1300)
  70 or/62-69 [TGF-a Terms] (7573)
  71 4 and 70 (0)
 72 exp Transforming Growth Factor beta/
(52202)
 73 transforming growth factor beta*.tw,kw.
(44111)
 74 transforming growth factor b*2.tw,kw.
(200)
  75 tgf-beta*.tw,kw. (54851)
  76 tgf-b*2.tw,kw. (527)
  77 tgfbeta*.tw,kw. (11183)
  78 tgfb*2.tw,kw. (3109)
 79 (platelet adj4 transforming growth fac-
tor*).tw,kw. (667)
 80 (bone derived adj4 transforming growth
factor*).tw,kw. (8)
  81 milk growth factor*.tw,kw. (24)
  82 Transforming Growth Factors/ (2367)
  83 or/72-82 [TGF-b Terms] (90052)
  84 4 and 83 (4)
  85 exp Growth Substances/ (707474)
  86 growth factor*.tw,kw. (316069)
  87 growth regulat*.tw,kw. (10005)
  88 growth substanc*.tw,kw. (508)
 89 “Intercellular Signaling Peptides and
Proteins”/ (23315)
  90 or/85-89 [Growth sub/Animal GS Terms]
(1007586)
  91 4 and 90 (206)
  92 Pituitary-Adrenal System/ (13648)
 93 Hypothalamo-Hypophyseal System/
(20362)
  94 92 and 93 (10492)
 95 (hypothalam* adj2 pituitar* adj2 adre-
nal*).tw,kw. (14564)
  96 HPA hormone*.tw,kw. (58)
  97 Corticotropin-Releasing Hormone/ (11355)
  98 (corticotropin releasing adj (hormone* or
factor*)).tw,kw. (10836)
  99 corticoliberin*.tw,kw. (159)
100 crf-41.tw,kw. (145)
101 crf41.tw,kw. (9)
102 CRH.tw,kw. (6220)
103 (acth releasing adj (hormone* or factor*))
.tw,kw. (51)
22 journals.sagepub.com/home/tab
02_TAB740076.indd 22
104 exp Growth Hormone-Releasing Hormone/
(4933)
105 (growth hormone releasing adj (hormone*
or factor*)).tw,kw. (3374)
106 somatocrinin*.tw,kw. (60)
107 somatoliberin*.tw,kw. (17)
108 hpgrf.tw,kw. (178)
109 ghrh.tw,kw. (3293)
110 Gonadotropin-Releasing Hormone/ (26158)
111 gonadotropin releasing hormone*.tw,kw.
(12740)
112 gonadorelin*.tw,kw. (221)
113 gonadoliberin*.tw,kw. (164)
114 gnrh.tw,kw. (19801)
115 gn-rh.tw,kw. (380)
116 luteinizing hormone releasing hormone*.
tw,kw. (5418)
117 luliberin*.tw,kw. (178)
118 (lh adj2 releasing hormone*).tw,kw.
(1853)
119 (lhfsh adj2 releasing hormone*).tw,kw.
(0)
120 lh-rh.tw,kw. (3307)
121 lhrh.tw,kw. (6255)
122 lhfshrh.tw,kw. (3)
123 lfrh.tw,kw. (3)
124 Thyrotropin-Releasing Hormone/
(12769)
125 (thyrotropin releasing adj (hormone* or
factor*)).tw,kw. (6959)
126 thyroliberin*.tw,kw. (456)
127 trh.tw,kw. (11230)
128 Pituitary Hormone-Releasing Hormones/
(3114)
129 exp Thyrotropin/ (30229)
130 thyrotropin*.tw,kw. (16865)
131 thyroid stimulating hormone*.tw,kw.
(10850)
132 TSH.tw,kw. (28136)
133 Adrenocorticotropic Hormone/ (48013)
134 (Adrenocorticotropic adj3 hormone*).
tw,kw. (7525)
135 ACTH.tw,kw. (36978)
136 exp Luteinizing Hormone/ (45646)
137 Luteinizing Hormone*.tw,kw. (27538)
138 interstitial cell-stimulating hormone*.
tw,kw. (100)
139 lh.tw,kw. (50271)
140 icsh.tw,kw. (405)
141 exp Follicle Stimulating Hormone/
(36262)
142 Follicle Stimulating Hormone*.tw,kw.
(17748)
143 FSH.tw,kw. (32350)
144 Gonadotropins, Pituitary/ (6582)
145 exp Testosterone/ (66499)
26/12/2017 4:00:34 PM

146 testosteron*.tw,kw. (75376)
147 exp Estradiol/ (79371)
148 estradiol*.tw,kw. (75793)
149 oestradiol*.tw,kw. (12797)
150 Hydrocortisone/ (67625)
151 hydrocortison*.tw,kw. (17704)
152 cortisol*.tw,kw. (54435)
153 epicortisol*.tw,kw. (21)
154 Prolactin/ (38745)
155 prolactin*.tw,kw. (42404)
156 pituitary mammotropic hormone*.tw,kw.
(2)
157 pituitary lactogenic hormone*.tw,kw. (33)
158 prl.tw,kw. (15849)
159 Thyroxine/ (35677)
160 thyroxin*.tw,kw. (29628)
161 lthyroxin*.tw,kw. (7)
162 thyrox*.tw,kw. (29650)
163 tyrosine*.tw,kw. (154357)
164 (t4 adj3 thyroid hormone*).tw,kw. (726)
165 Neurotransmitter Agents/ (26591)
166 neurohormone*.tw,kw. (3022)
167 neuro-hormone*.tw,kw. (57)
168 neuroendocrine hormone*.tw,kw. (331)
169 neuro-endocrine hormone*.tw,kw. (7)
170 neuropeptides/ (24351)
171 neuropeptide*.tw,kw. (39401)
172 neuro-peptide*.tw,kw. (64)
173 or/94-172 [HPA Hormones Terms]
(709727)
174 4 and 173 (408)
175 Calcitonin Gene-Related Peptide*.tw,kw.
(10352)
176 CGRP.tw,kw. (8801)
177 Calcitonin Gene-Related Peptide/
(10955)
178 or/175-177 [CGRP Terms] (14822)
179 4 and 178 (12)
180 Substance P/ (16556)
181 substance p*2.tw,kw. (21651)
182 “sp(1-11)”.tw,kw. (30)
183 sub-p*2.tw,kw. (698)
184 or/180-183 [Sub-P Terms] (24608)
185 4 and 184 (91)
186 (brain adj3 metabolit*).tw,kw. (2389)
187 brain/me (134766)
188 or/186-187 [Brain metabolite Terms]
(136039)
189 4 and 188 (33)
190 Neurotransmitter Agents/ (26591)
191 neurotransmitter*.tw,kw. (61107)
192 neuroregulator*.tw,kw. (458)
193 neuromodulator*.tw,kw. (8532)
194 neurohumor*.tw,kw. (3776)
195 nerve transmitter*.tw,kw. (44)
196 neuro transmitter*.tw,kw. (141)
journals.sagepub.com/home/tab 23
02_TAB740076.indd 23
D Kumbhare, S Ahmed et al.
197 neuro regulator*.tw,kw. (20)
198 neuro modulator*.tw,kw. (63)
199 neuro humor*.tw,kw. (258)
200 NT.tw,kw. (32894)
201 or/190-200 [NT Terms] (118788)
202 4 and 201 (195)
203 Serotonin/ (65738)
204 serotonin*.tw,kw. (89169)
205 5-hydroxytryptamine*.tw,kw. (20767)
206 5hydroxytryptamine*.tw,kw. (4)
207 5-ht.tw,kw. (35796)
208 5ht.tw,kw. (3638)
209 hippophaine*.tw,kw. (1)
210 enteramine*.tw,kw. (91)
211 exp Dopamine/ (72455)
212 dopamine*.tw,kw. (137358)
213 hydroxytyramine*.tw,kw. (85)
214 dihydroxyphenethylamine*.tw,kw. (54)
215 exp Norepinephrine/ (84410)
216 methoxynoradrenaline*.tw,kw. (1)
217 metadrenaline*.tw,kw. (70)
218 normetadrenaline*.tw,kw. (50)
219 Norepinephrine*.tw,kw. (54056)
220 noradrenaline*.tw,kw. (36004)
221 noradrenalin*.tw,kw. (37562)
222 Epinephrine/ (53789)
223 epinephrine*.tw,kw. (36758)
224 adrenalin*.tw,kw. (21615)
225 adrenaline*.tw,kw. (18628)
226 epifrin*.tw,kw. (3)
227 metadrenaline*.tw,kw. (70)
228 metanephrine*.tw,kw. (1265)
229 Melatonin/ (17360)
230 N-acetyl-5-methoxy tryptamine.tw,kw.
(19)
231 Melatonin*.tw,kw. (20941)
232 Catecholamines/ (35231)
233 catecholamine*.tw,kw. (57751)
234 sympathin*.tw,kw. (85)
235 Biogenic Monoamines/ (3486)
236 monoamine*.tw,kw. (31317)
237 gamma-Aminobutyric Acid/ (35956)
238 gamma aminobutyric acid*.tw,kw.
(22499)
239 gaba.tw,kw. (48856)
240 gammalon*.tw,kw. (9)
241 aminalon*.tw,kw. (20)
242 4-aminobutyric acid*.tw,kw. (185)
243 4-aminobutanoic acid*.tw,kw. (32)
244 y-aminobutyric acid*.tw,kw. (48)
245 Glutamic Acid/ (35530)
246 glutamate.tw,kw. (92033)
247 glutamic.tw,kw. (26711)
248 Glu.tw,kw. (26545)
249 or/203-248 [NT Terms continued]
(620917)
26/12/2017 4:00:34 PM
 Therapeutic Advances in Musculoskeletal Disease 10(1)

250 4 and 249 (799)   27 neurite outgrowth factor*.tw,kw. (0)

251 Biomarkers/ (209394)   28 neuronotrophic factor*.tw,kw. (0)
252 biomarker*.tw,kw. (168003)   29 neuronal growth-associated protein*.
253 (bio* adj3 marker*).tw,kw. (28734) tw,kw. (1)
254 (clinical adj3 marker*).tw,kw. (9163)   30 or/20-29 [NGF Terms] (760)
255 (surrogate adj3 endpoint).tw,kw. (791)   31 4 and 30 (7)
256 (surrogate adj3 end point*).tw,kw. (1107)   32 Brain-Derived Neurotrophic Factor/ (190)
257 (surrogate adj3 marker*).tw,kw. (10668)   33 brain derived neurotrophic factor*.tw,kw.
258 (laboratory adj3 marker*).tw,kw. (2143) (375)
259 (serum adj3 marker*).tw,kw. (13751)   34 bdnf*1.tw,kw. (387)
260 or/251-259 [General Biomarker Terms]   35 or/32-34 [BDNF Terms] (457)
(368274)   36 4 and 35 (3)
261 4 and 260 (261)   37 Insulin-Like Growth Factor I/ (1521)
262 19 or 31 or 36 or 48 or 61 or 71 or 84 or   38 insulin like growth factor I.tw,kw. (787)
91 or 174 or 179 or 185 or 189 or 202 or   39 insulin like growth factor 1.tw,kw. (547)
250 or 261 (1608)   40 igf-i.tw,kw. (1337)
263 262 not (exp animal/ not exp humans/)   41 igf-1.tw,kw. (801)
(1573)   42 somatomedin c.tw,kw. (253)
264 limit 263 to english language (1456)   43 insulin-like somatomedin peptide i.tw,kw.
265 limit 264 to yr=“1990 -Current” (1420) (0)
 44 insulin-like somatomedin peptide 1.tw,
kw. (0)
***************************   45 exp Somatomedins/ (1567)
Database: EBM Reviews - Cochrane Central   46 Somatomedin*.tw,kw. (327)
Register of Controlled Trials <February   47 or/37-46 [IGF Terms] (2858)
2017>   48 4 and 47 (16)
Search Strategy:   49 Growth Hormone/ (1708)
--------------------------------------------------------------------------------   50 Human Growth Hormone/ (1448)
  51 [Somatotropin.rn.] (0)
  1 Fibromyalgia/ (664)   52 Growth Hormone*.tw,kw. (4160)
  2 Fibromyalgi*.tw,kw. (1374)   53 somatotropin*.tw,kw. (64)
  3 fibrositis*.tw,kw. (60)   54 somatropin*.tw,kw. (49)
  4 or/1-3 (1442)   55 GH.tw,kw. (3265)
   5 exp Reactive Oxygen Species/ (1211)   56 HGH.tw,kw. (279)
   6 reactive oxygen spec*.tw,kw. (736)   57 RHGH.tw,kw. (417)
  7 ROS*1.tw,kw. (5341)   58 “HGH(m)”.tw,kw. (0)
   8 active oxygen*.tw,kw. (16)   59 “rHGH(m)”.tw,kw. (1)
   9 pro oxidant*.tw,kw. (89)   60 or/49-59 [GH Terms] (5223)
  10 prooxidant*.tw,kw. (43)   61 4 and 60 (19)
  11 oxygen radical*.tw,kw. (218)   62 Transforming Growth Factor alpha/ (22)
  12 Hydroxyl Radical*.tw,kw. (52)  63 transforming growth factor alpha.tw,kw.
  13 hypochlorous acid*.tw,kw. (9) (44)
  14 hypochlorite*.tw,kw. (283)   64 transforming growth factor a.tw,kw. (574)
  15 peroxide*.tw,kw. (1570)   65 tgf-alpha.tw,kw. (36)
  16 singlet oxygen*.tw,kw. (19)   66 tgf-a.tw,kw. (723)
  17 singlet dioxygen*.tw,kw. (0)   67 tgfalpha.tw,kw. (10)
  18 or/5-17 [ROS terms] (8296)   68 tgfa.tw,kw. (14)
  19 4 and 18 (4)   69 (epidermal adj4 transforming growth fac-
  20 Nerve Growth Factors/ (121) tor*).tw,kw. (14)
  21 Nerve Growth Factor/ (57)   70 or/62-69 [TGF-a Terms] (962)
  22 ngf.tw,kw. (121)   71 4 and 70 (0)
  23 nerve growth factor*.tw,kw. (175)  72 exp Transforming Growth Factor beta/
  24 neurotrophin*.tw,kw. (80) (373)
  25 neurotrophic protein*.tw,kw. (3)  73 transforming growth factor beta*.tw,kw.
  26 neurotrophic factor*.tw,kw. (465) (519)

24 journals.sagepub.com/home/tab

02_TAB740076.indd 24 26/12/2017 4:00:34 PM


 74 transforming growth factor b*2.tw,kw.
(17)
  75 tgf-beta*.tw,kw. (637)
  76 tgf-b*2.tw,kw. (51)
  77 tgfbeta*.tw,kw. (115)
  78 tgfb*2.tw,kw. (44)
 79 (platelet adj4 transforming growth fac-
tor*).tw,kw. (21)
 80 (bone derived adj4 transforming growth
factor*).tw,kw. (0)
  81 milk growth factor*.tw,kw. (0)
  82 Transforming Growth Factors/ (4)
  83 or/72-82 [TGF-b Terms] (1082)
  84 4 and 83 (0)
  85 exp Growth Substances/ (19004)
  86 growth factor*.tw,kw. (7786)
  87 growth regulat*.tw,kw. (38)
  88 growth substanc*.tw,kw. (11)
 89 “Intercellular Signaling Peptides and
Proteins”/ (209)
  90 or/85-89 [Growth sub/Animal GS Terms]
(26394)
  91 4 and 90 (33)
  92 Pituitary-Adrenal System/ (628)
  93 Hypothalamo-Hypophyseal System/ (649)
  94 92 and 93 (544)
 95 (hypothalam* adj2 pituitar* adj2 adre-
nal*).tw,kw. (1034)
  96 HPA hormone*.tw,kw. (6)
  97 Corticotropin-Releasing Hormone/ (225)
  98 (corticotropin releasing adj (hormone* or
factor*)).tw,kw. (294)
  99 corticoliberin*.tw,kw. (0)
100 crf-41.tw,kw. (3)
101 crf41.tw,kw. (2)
102 CRH.tw,kw. (277)
103 (acth releasing adj (hormone* or factor*))
.tw,kw. (6)
104 exp Growth Hormone-Releasing Hormone/
(333)
105 (growth hormone releasing adj (hormone*
or factor*)).tw,kw. (259)
106 somatocrinin*.tw,kw. (2)
107 somatoliberin*.tw,kw. (0)
108 hpgrf.tw,kw. (8)
109 ghrh.tw,kw. (412)
110 Gonadotropin-Releasing Hormone/ (1152)
111 gonadotropin releasing hormone*.tw,kw.
(974)
112 gonadorelin*.tw,kw. (424)
113 gonadoliberin*.tw,kw. (4)
114 gnrh.tw,kw. (2139)
115 gn-rh.tw,kw. (16)
116 luteinizing hormone releasing hormone*.
tw,kw. (302)
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117 luliberin*.tw,kw. (1)
118 (lh adj2 releasing hormone*).tw,kw. (69)
119 (lhfsh adj2 releasing hormone*).tw,
kw. (0)
120 lh-rh.tw,kw. (149)
121 lhrh.tw,kw. (412)
122 lhfshrh.tw,kw. (0)
123 lfrh.tw,kw. (0)
124 Thyrotropin-Releasing Hormone/ (295)
125 (thyrotropin releasing adj (hormone* or
factor*)).tw,kw. (264)
126 thyroliberin*.tw,kw. (4)
127 trh.tw,kw. (483)
128 Pituitary Hormone-Releasing Hormones/
(33)
129 exp Thyrotropin/ (792)
130 thyrotropin*.tw,kw. (773)
131 thyroid stimulating hormone*.tw,kw.
(513)
132 TSH.tw,kw. (1370)
133 Adrenocorticotropic Hormone/ (1247)
134 (Adrenocorticotropic adj3 hormone*).
tw,kw. (481)
135 ACTH.tw,kw. (1791)
136 exp Luteinizing Hormone/ (1555)
137 Luteinizing Hormone*.tw,kw. (1694)
138 interstitial cell-stimulating hormone*.
tw,kw. (1)
139 lh.tw,kw. (2679)
140 icsh.tw,kw. (3)
141 exp Follicle Stimulating Hormone/ (1758)
142 Follicle Stimulating Hormone*.tw,kw.
(1458)
143 FSH.tw,kw. (2696)
144 Gonadotropins, Pituitary/ (76)
145 exp Testosterone/ (2259)
146 testosteron*.tw,kw. (4121)
147 exp Estradiol/ (3568)
148 estradiol*.tw,kw. (5292)
149 oestradiol*.tw,kw. (1036)
150 Hydrocortisone/ (5011)
151 hydrocortison*.tw,kw. (2910)
152 cortisol*.tw,kw. (7255)
153 epicortisol*.tw,kw. (0)
154 Prolactin/ (1618)
155 prolactin*.tw,kw. (2766)
156 pituitary mammotropic hormone*.tw,
kw. (0)
157 pituitary lactogenic hormone*.tw,kw. (0)
158 prl.tw,kw. (852)
159 Thyroxine/ (820)
160 thyroxin*.tw,kw. (1063)
161 lthyroxin*.tw,kw. (2)
162 thyrox*.tw,kw. (1064)
163 tyrosine*.tw,kw. (1988)
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 Therapeutic Advances in Musculoskeletal Disease 10(1)
164 (t4 adj3 thyroid hormone*).tw,kw. (32)
165 Neurotransmitter Agents/ (237)
166 neurohormone*.tw,kw. (205)
167 neuro-hormone*.tw,kw. (1)
168 neuroendocrine hormone*.tw,kw. (16)
169 neuro-endocrine hormone*.tw,kw. (0)
170 neuropeptides/ (100)
171 neuropeptide*.tw,kw. (660)
172 neuro-peptide*.tw,kw. (2)
173 or/94-172 [HPA Hormones Terms] (30462)
174 4 and 173 (35)
175 Calcitonin Gene-Related Peptide*.tw,kw.
(256)
176 CGRP.tw,kw. (224)
177 Calcitonin Gene-Related Peptide/ (128)
178 or/175-177 [CGRP Terms] (308)
179 4 and 178 (2)
180 Substance P/ (166)
181 substance p*2.tw,kw. (395)
182 “sp(1-11)”.tw,kw. (0)
183 sub-p*2.tw,kw. (339)
184 or/180-183 [Sub-P Terms] (750)
185 4 and 184 (8)
186 (brain adj3 metabolit*).tw,kw. (89)
187 brain/me (88)
188 or/186-187 [Brain metabolite Terms] (175)
189 4 and 188 (1)
190 Neurotransmitter Agents/ (237)
191 neurotransmitter*.tw,kw. (974)
192 neuroregulator*.tw,kw. (11)
193 neuromodulator*.tw,kw. (207)
194 neurohumor*.tw,kw. (339)
195 nerve transmitter*.tw,kw. (0)
196 neuro transmitter*.tw,kw. (6)
197 neuro regulator*.tw,kw. (2)
198 neuro modulator*.tw,kw. (2)
199 neuro humor*.tw,kw. (9)
200 NT.tw,kw. (1642)
201 or/190-200 [NT Terms] (3293)
202 4 and 201 (13)
203 Serotonin/ (924)
204 serotonin*.tw,kw. (5531)
205 5-hydroxytryptamine*.tw,kw. (694)
206 5hydroxytryptamine*.tw,kw. (0)
207 5-ht.tw,kw. (1325)
208 5ht.tw,kw. (205)
209 hippophaine*.tw,kw. (0)
210 enteramine*.tw,kw. (0)
211 exp Dopamine/ (1070)
212 dopamine*.tw,kw. (5405)
Visit SAGE journals online
213 hydroxytyramine*.tw,kw. (0)
journals.sagepub.com/ 214 dihydroxyphenethylamine*.tw,kw. (1)
home/tab
215 exp Norepinephrine/ (2472)
SAGE journals 216 methoxynoradrenaline*.tw,kw. (0)
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217 metadrenaline*.tw,kw. (2)
218 normetadrenaline*.tw,kw. (2)
219 Norepinephrine*.tw,kw. (3401)
220 noradrenaline*.tw,kw. (1701)
221 noradrenalin*.tw,kw. (2271)
222 Epinephrine/ (2877)
223 epinephrine*.tw,kw. (4260)
224 adrenalin*.tw,kw. (2698)
225 adrenaline*.tw,kw. (1898)
226 epifrin*.tw,kw. (0)
227 metadrenaline*.tw,kw. (2)
228 metanephrine*.tw,kw. (42)
229 Melatonin/ (773)
230 N-acetyl-5-methoxy tryptamine.tw,kw. (1)
231 Melatonin*.tw,kw. (1355)
232 Catecholamines/ (980)
233 catecholamine*.tw,kw. (2798)
234 sympathin*.tw,kw. (1)
235 Biogenic Monoamines/ (38)
236 monoamine*.tw,kw. (1001)
237 gamma-Aminobutyric Acid/ (916)
238 gamma aminobutyric acid*.tw,kw. (348)
239 gaba.tw,kw. (804)
240 gammalon*.tw,kw. (3)
241 aminalon*.tw,kw. (1)
242 4-aminobutyric acid*.tw,kw. (156)
243 4-aminobutanoic acid*.tw,kw. (0)
244 y-aminobutyric acid*.tw,kw. (4)
245 Glutamic Acid/ (232)
246 glutamate.tw,kw. (1038)
247 glutamic.tw,kw. (487)
248 Glu.tw,kw. (286)
249 or/203-248 [NT Terms continued]
(26653)
250 4 and 249 (146)
251 Biomarkers/ (10511)
252 biomarker*.tw,kw. (10630)
253 (bio* adj3 marker*).tw,kw. (5248)
254 (clinical adj3 marker*).tw,kw. (903)
255 (surrogate adj3 endpoint).tw,kw. (96)
256 (surrogate adj3 end point*).tw,kw. (142)
257 (surrogate adj3 marker*).tw,kw. (902)
258 (laboratory adj3 marker*).tw,kw. (146)
259 (serum adj3 marker*).tw,kw. (1746)
260 or/251-259 [General Biomarker Terms]
(23066)
261 4 and 260 (36)
262 19 or 31 or 36 or 48 or 61 or 71 or 84 or
91 or 174 or 179 or 185 or 189 or 202 or
250 or 261 (233)
263 262 not (exp animal/ not exp humans/)
(233)
264 limit 263 to english language (205)
265 limit 264 to yr=“1990 -Current” (203)
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