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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:


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

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Therapeutic Advances in Musculoskeletal Disease 10(1)

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-
Figure 1.  Factors contributing to diagnostic
ated with the creation of the 1990 classification
heterogeneity in clinical groups. 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-
possible that the current fibromyalgia population nostic heterogeneity.
is composed of patients who may present primar-
ily with depression, a sleep disorder, a cognitive The 1990 classification criteria were developed
affective disorder or a somatic disorder along with through consensus from fibromyalgia experts
a limited amount of muscle aches and pain.2–4 using clinical observations and assessments.1
Symptoms such as pain, fatigue, sleep distur- Criteria developed through expert consensus
bances, cognitive difficulties and depression are increases the chances for misdiagnosis because
nonspecific and can also be caused by different they are limited to information available to the
pathophysiological mechanisms. expert at that time, which may not be compre-
hensive, and is biased by their internal concept of
Current literature shows that the tender point the disorder which is dependent on their clinical
count criterion has been shown to poorly differen- experience.19 These types of criteria also vary
tiate between fibromyalgia and other pain disor- across time and countries, where different repre-
ders such as myofascial pain syndrome.9,10 Gerwin sentations of the same condition are accepted.19
and colleagues11,12 also report the clinical presence Therefore, the sensitivity of 88.4% and specificity
of tender points in 79% of patients with myofas- of 81.1% reported for the 1990 criteria may not
cial pain syndrome and an overlap with fibromyal- have been accurate. The 2010 criteria were devel-
gia of approximately 40%. Additionally, the tender oped using the 1990 criteria as the reference
point count is typically higher in women relative to standard.2 Since the 1990 criteria are not a per-
men, therefore more women are likely to be diag- fect diagnostic tool, the chance of error when
nosed with fibromyalgia.13,14 Jones and colleagues15 developing the 2010 criteria increased. No statis-
found that more women were diagnosed with tical adjustments were used to determine accu-
fibromyalgia relative to men using the 1990, 2010 racy rates reflective of the variability in physician
and modified 2010 criteria. However, the preva- and assessor judgments for both the 1990 and
lence of women with fibromyalgia relative to men 2010 criteria. The 2011 modification used a dif-
using the 1990 criteria, which utilizes only the ten- ferent reference standard than the previous crite-
der point count, was 13.7 fold and was lower for ria, the National Data Bank of Rheumatic
the other criteria. Several studies have delineated Diseases, in which the fibromyalgia population
clinical subgroups among patients with fibromyal- was determined by many different clinicians with
gia diagnosed with the 1990 criteria, which is con- undefined diagnostic methods. This further
sidered the most specific definition of fibromyalgia, 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 limited by the methodological shortcomings of
were an improvement of the 2010/2011 criteria, the previous criteria. Table 1 contains methodo-
as they addressed shortcomings of the 2010/2011 logical measures that should be comprehensively
criteria when validated relative to the 1990 crite- evaluated when developing a diagnostic method,
ria and clinical diagnosis. They are however still 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 Findings on pathophysiological


diagnostic criteria based on the reports of Wolfe perturbations in fibromyalgia
and colleagues.1,2 Research elucidating the pathophysiology of
fibromyalgia provides some promising avenues
Wolfe and colleagues4 reviewed studies that vali- for novel diagnostic markers. There is a growing
dated the 2010 and 2011 criteria against the 1990 body of evidence suggesting links between chronic
criteria. They found several studies that accom- pain and central sensitization, including lower
plished this. Bidari and colleagues22 validated the pain thresholds and hyperalgesia.25,26 Widespread
2010 criteria against the 1990 criteria by using hyperalgesia differentiates fibromyalgia from
dolorimetry to characterize tender points. They other states of central sensitization, however it
sampled 168 patients with fibromyalgia and 100 does not yet have the capacity to differentiate it
controls in Iran. They found that the 2010 crite- from other similarly presenting disorders with or
ria had 79.1% accuracy when using the 1990 cri- without the presence of central sensitization, such
teria as the gold standard. Carrillo-de-la-Peña as myofascial pain syndrome.26,29
and colleagues23 validated the Spanish version of
the 2010 criteria against the 1990 criteria. They Several biological mechanisms have been impli-
recruited 80 patients with fibromyalgia and 59 cated in the development of the sensitized state in
healthy control Spanish participants. They used fibromyalgia. Biomarkers associated with these
algometry to identify tender points. They found mechanisms are shared between several disorders
an inter-criteria agreement of 0.73 between the and can be used to develop cutoffs specific to
2010 and 1990 criteria. Usui and colleagues24 fibromyalgia relative to other conditions. A com-
assessed the validity of the Japanese version of the prehensive systematic search of Medline, Central
2010 criteria relative to the 1990 criteria. They (including Medline ePub Ahead of Print,
recruited 94 patients with 1990 defined fibromy- In-Process, and Other Non-Indexed Citations),
algia and 43 controls from Japan. They found a and EMBASE was conducted to determine the
sensitivity of 82% when comparing the 2010 cri- mechanisms that led to or are associated with the
teria with the 1990 criteria. There is a general sensitized state in patients diagnosed with the
decrease in accuracy measures when comparing current definition of fibromyalgia. The complete
the 2010/2011 criteria with the 1990 criteria.4 search strategy includes a comprehensive list of
subject headings and text words to describe
The current challenge facing researchers and cli- ‘fibromyalgia’ and various classes of biomarkers;
nicians is to identify a diagnostic marker indica- this can be found in Appendix A. Studies assess-
tive of a causal mechanism associated with ing the presence of biomarkers (or lack thereof) in
fibromyalgia to increase the accuracy of diagno- fibromyalgia typically used the 1990 criteria to
sis. Current research suggests that central sensiti- diagnose their clinical population. The search
zation is a primary candidate representative of the indicated that hypothalamic pituitary axis (HPA)
pathophysiology underlying fibromyalgia.25,26 hormones, immune and inflammatory markers,
The current criteria were not constructed to be neuropeptides and neurohormones, and advanced
specific to people with central sensitization but brain imaging were the most investigated diag-
rather individuals with a cluster of symptoms that nostic markers indicative of central sensitization
expert panels of clinicians have defined as fibro- and fibromyalgia. Here we present a brief sum-
myalgia. The criteria likely diagnose a consistent mary of our literature search findings.
spectrum of patients; however, they may not cap-
ture the true presence of fibromyalgia. The spe- HPA hormone perturbations are present in fibro-
cific mechanism responsible for the sensitization myalgia and other related disorders with suspected
associated with fibromyalgia development should underlying central sensitization such as major
be elucidated since central sensitization has mul- depressive disorder, post-traumatic stress disorder
tiple etiologies (e.g. bacterial infection, inflamma- (PTSD) or chronic fatigue syndrome. The combi-
tion, etc.).27,28 This should allow for the separation nation of adrenocorticotropic releasing hormone
of the overall population based upon the underly- (ACTH) and cortisol levels in fibromyalgia pre-
ing mechanism into specific clinical groups each sents a distinct profile capable of differentiating it
with a unique underlying pathology and a consist- from other disorders. There is growing consensus
ent set of symptoms. The following section pre- in the literature that high ACTH levels suggest
sents findings on potential pathophysiological hyper responsiveness in pituitary release in
indicators of fibromyalgia. response to corticotropin releasing hormone

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D Kumbhare, S Ahmed et al.

(CRH). This has been confirmed using exogenous blood flow to brain areas associated with inducing
infusions of CRH. Plasma or 24 h urinary cortisol analgesic effects, and increased activity in the pri-
levels are normal to low in people with fibromyal- mary and secondary somatosensory cortices in
gia, indicating hyporesponsivenes at the adrenal people with fibromyalgia.51 This suggests that
glands to ACTH.30–37 In depression and PTSD, their nervous system is compensating for the
cortisol levels are chronically elevated whereas in increase in nociceptive signals received from the
chronic fatigue syndrome cortisol and ACTH lev- spinal cord and is being subject to hypermetabolic
els are normal.37–40 Evening cortisol levels have states due to large amounts of sustained afferent
been shown to be higher than normal in fibromy- input. Increases in the glutamate to glutamine
algia and lower than normal in chronic fatigue ratio are positively associated with the degree of
syndrome.39,41 These factors provide evidence of functional connectivity and metabolism in brain
differences in HPA regulation between fibromyal- areas implicated in central sensitization and fibro-
gia and other central sensitization disorders. myalgia.53,54 Decreases in dopamine binding and
precursor uptake are also associated with the
Total oxidative status and immune responses are attentional and pain processing abnormalities
also high in fibromyalgia.42 The presence of observed in fibromyalgia.55,56
antiserotonin antibodies is more common
between fibromyalgia and chronic fatigue syn- These findings point to a multi axial interaction
drome relative to other disorders.43 Polymorphisms between neurological, endocrine and immune
in genes coding for serotonin transporters and systems that results in the development of central
catechol-o-methyl transferase are associated with sensitization in fibromyalgia. We suggest the
high pain sensitivity in fibromyalgia. These find- development of new diagnostic criteria that are
ings suggest there may be a neuroimmune basis to based upon clinical and central sensitization
this disorder. A robust effect demonstrated in attributes that better characterize fibromyalgia.
several studies suggests that levels of interleukin At present, the application of the diagnostic crite-
(IL)-6, IL-8 and IL-10 are high in fibromyalgia ria will result in a heterogeneous group that con-
relative to healthy normal or other pain and cen- sists of subgroups.
tral sensitivity disorders.44–46 Furthermore, tumor
necrosis factor α has been consistently elevated in
disorders of central sensitization, including fibro- Discussion
myalgia.45,47–49 Positive correlations exist between Given these findings, researchers should strive
these inflammatory markers and clinical symp- towards creating subgroups within patients diag-
tom severity. Zanette and colleagues50 identified a nosed by the current criteria or those with central
strong correlation between increased serum sensitization, using some of the well researched
brain-derived neurotrophic factor and S100B biomarkers. This should identify distinct underly-
protein levels, which is associated with the coex- ing pathophysiological mechanisms among the
istence of neurological disease and central sensi- patients and create novel groups, one of which
tivity syndrome, with lower pressure pain should be fibromyalgia. For example, biomarkers
thresholds in patients with fibromyalgia. Their that are common to fibromyalgia and other disor-
findings provide a significant initial step towards ders, such as cortisol, can be used to develop
developing biomarkers diagnostic of fibromyal- diagnostic cutoffs that help to create better
gia, ultimately to create a well defined group and boundaries for each condition and thus improve
clinical definition. their distinct definitions. Biomarkers may also be
used to understand whether fibromyalgia is truly
Advanced brain imaging in fibromyalgia has dem- a singular entity or a psychosomatic manifestation
onstrated increases in functional connectivity of a spectrum disorder continuous with other psy-
between anatomical cortical regions associated chiatric and pain conditions such as depression,
with attention, emotion and somatosensory pro- chronic fatigue syndrome or myofascial pain syn-
cessing, including the anterior cingulate cortex, drome. A cluster analysis or discriminative func-
anterior prefrontal cortex, parietal cortex, dorso- tion analysis may be used to create a set of criteria
lateral prefrontal cortex and the insula.51 Increases that diagnose a homogenous group representing
in functional connectivity between these areas is fibromyalgia. Clinical signs and symptoms in
associated with symptom (pain, depression) sever- combination with indicators of pathophysiologi-
ity and pain duration in fibromyalgia.52 There cal mechanisms known to be associated with
have also been studies demonstrating attenuated fibromyalgia and overlapping disorders should be

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Therapeutic Advances in Musculoskeletal Disease 10(1)

included. These analyses may inform which vari- than a mechanistic approach taken towards its
ables are highly predictive of overlapping disor- diagnosis and treatment.64 This method of diag-
ders and whether there is a boundary that nosis results in the presence of different clinical
separates symptomatically overlapping condi- subgroups presenting different pathophysiologi-
tions. Following this, the predictive ability of a cal mechanisms under a single pain disorder
biomarker profile that can differentiate fibromyal- diagnosis, as is present in fibromyalgia. Many
gia from other central sensitization disorders patients may be receiving treatments that may
should be undertaken. not be suitable for their presenting condition.
There is a need for well defined mechanism-
Ideally, selected biomarker panels should be able based criteria to describe the specific characteris-
to diagnose fibromyalgia during its earlier phases, tics of fibromyalgia. This should guide the
during a routine exam or in the presence of ques- development of more accurate diagnostic meth-
tionable symptoms.57–59 The biomarker panel ods and effective treatments.
profile should indicate the stage or severity of the
disorder, be responsive to clinical change and Author’s Note
thereby allow for earlier intervention and preven- Dinesh Kumbhare and Sara Ahmed are First
tion of progression. Ideally, the biomarker panel Co-Authors of the article.
should also be responsive to the initiation, con-
tinuation, or cessation of external interventions as Funding
this will indicate the patient’s responsiveness to This research received no specific grant from any
these interventions. This should address the limi- funding agency in the public, commercial, or not-
tation presented by the 2010 and subsequent cri- for-profit sectors.
teria, whereby they measure the severity of a
patient who already has fibromyalgia symptoms Conflict of interest statement
rather than to recognize the presence of the disor- The authors declare that there is no conflict of
der at any of its stages. interest.

In addition to these disease-specific attributes,


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38. Bazzichi L, Rossi A, Zirafa C, et al. Thyroid patterns in fibromyalgia and their correlation with
autoimmunity may represent a predisposition for clinical manifestations. Clin Exp Rheumatol 2007;
the development of fibromyalgia? Rheumatol Int 25: 225–230.
2012; 32: 335–341.
50. Zanette SA, Dussan-Sarria JA, Souza A, et al.
39. Crofford LJ, Young EA, Engleberg NC, et al. Higher serum S100B and BDNF levels are
Basal circadian and pulsatile ACTH and cortisol correlated with a lower pressure-pain threshold in
secretion in patients with fibromyalgia and/or fibromyalgia. Mol Pain 2014; 10: 46.
chronic fatigue syndrome. Brain Behav Immun
51. Williams DA and Gracely RH. Biology and
2004; 18: 314–325.
therapy of fibromyalgia. Functional magnetic
40. Holsboer F, Gerken A, Stalla GK, et al. ACTH, resonance imaging findings in fibromyalgia.
cortisol, and corticosterone output after ovine Arthritis Res Ther 2007; 8: 224.
corticotropin-releasing factor challenge during 52. Truini A, Tinelli E, Gerardi MC, et al. Abnormal
depression and after recovery. Biol Psychiatry resting state functional connectivity of the
1985; 20: 276–286. periaqueductal grey in patients with fibromyalgia.
41. Fatima G, Das SK, Mahdi AA, et al. Circadian Clin Exp Rheumatol 2016; 34(2 Suppl. 96):
rhythm of serum cortisol in female patients with 129–133.
fibromyalgia syndrome. Indian J Clin Biochem 53. Feraco P, Bacci A, Pedrabissi F, et al. Metabolic
2013; 28: 181–184. abnormalities in pain-processing regions of patients
42. Bozkurt M, Caglayan M, Oktayoglu P, et al. with fibromyalgia: a 3T MR spectroscopy study.
Serum prolidase enzyme activity and oxidative AJNR Am J Neuroradiol 2011; 32: 1585–1590.
status in patients with fibromyalgia. Redox Rep 54. Fayed N, Andres E, Rojas G, et al. Brain
2014; 19: 148–153. dysfunction in fibromyalgia and somatization
disorder using proton magnetic resonance
43. Klein R and Berg PA. High incidence of
spectroscopy: a controlled study. Acta Psychiatr
antibodies to 5-hydroxytryptamine, gangliosides
Scand 2012; 126: 115–125.
and phospholipids in patients with chronic fatigue
and fibromyalgia syndrome and their relatives: 55. Potvin S, Larouche A, Normand E, et al. DRD3
evidence for a clinical entity of both disorders. Ser9Gly polymorphism is related to thermal pain
Eur J Med Res 1995; 1: 21–26. perception and modulation in chronic widespread

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D Kumbhare, S Ahmed et al.

pain patients and healthy controls. J Pain 2009;   10 prooxidant*.tw,kw. (2705)


10: 969–975.   11 oxygen radical*.tw,kw. (8512)
56. Wood PB, Patterson JC, Sunderland JJ, et al.   12 Hydroxyl Radical*.tw,kw. (15891)
Reduced presynaptic dopamine activity in   13 hypochlorous acid*.tw,kw. (1866)
fibromyalgia syndrome demonstrated with   14 hypochlorite*.tw,kw. (5723)
positron emission tomography: a pilot study. J   15 peroxide*.tw,kw. (62557)
Pain 2007; 8: 51–58.   16 singlet oxygen*.tw,kw. (6764)
57. Biomedical FAST. NIH definition of biomarker.   17 singlet dioxygen*.tw,kw. (19)
Clin Pharmacol Ther 2001; 69: 89–95.   18 or/5-17 [ROS terms] (318259)
  19 4 and 18 (49)
58. Coriell Institute for Medical Research.   20 Nerve Growth Factors/ (19795)
Characteristics of the ideal biomarker, https://
  21 Nerve Growth Factor/ (6367)
www.coriell.org/research-services/biomarkers/
characteristics-of-the-ideal-biomarker
  22 ngf.tw,kw. (14151)
  23 nerve growth factor*.tw,kw. (17267)
59. NCSS Fact Finding Cardiotoxicity Expert   24 neurotrophin*.tw,kw. (10853)
Working Group. https://www.fda.gov/ohrms/   25 neurotrophic protein*.tw,kw. (130)
dockets/ac/01/briefing/3798b1_04_HOLT.PPT   26 neurotrophic factor*.tw,kw. (23498)
60. Fischer AA. Algometry in diagnosis of   27 neurite outgrowth factor*.tw,kw. (37)
musculoskeletal pain and evaluation of treatment   28 neuronotrophic factor*.tw,kw. (153)
outcome: an update. J Musculoskeletal Pain 1998;   29 neuronal growth-associated protein*.
6: 5–32. tw,kw. (63)
61. King CD, Mano KE, Barnett KA, et al. Pressure   30 or/20-29 [NGF Terms] (52362)
pain threshold and anxiety in adolescent females   31 4 and 30 (36)
with and without juvenile fibromyalgia: a pilot   32 Brain-Derived Neurotrophic Factor/
study. Clin J Pain 2017; 33: 620–626. (12600)
62. Borg-Stein J and Simons DG. Myofascial pain.
  33 brain derived neurotrophic factor*.tw,kw.
Arch Phys Med Rehabil 2002; 83: S40–S47. (14020)
  34 bdnf*1.tw,kw. (15555)
63. Maier C, Baron R, Tölle TR, et al. Quantitative   35 or/32-34 [BDNF Terms] (19119)
sensory testing in the German Research Network   36 4 and 35 (20)
on Neuropathic Pain (DFNS): somatosensory
  37 Insulin-Like Growth Factor I/ (31283)
abnormalities in 1236 patients with different
neuropathic pain syndromes. Pain 2010; 150:
  38 insulin like growth factor I.tw,kw. (14082)
439–450.   39 insulin like growth factor 1.tw,kw. (11139)
  40 igf-i.tw,kw. (21983)
64. Simon LS. Relieving pain in America: a blueprint   41 igf-1.tw,kw. (13669)
for transforming prevention, care, education, and   42 somatomedin c.tw,kw. (1084)
research. J Pain Palliat Care Pharmacother 2012;
  43 insulin-like somatomedin peptide i.tw,kw. (0)
26: 197–198.
  44 insulin-like somatomedin peptide
1.tw,kw. (0)
  45 exp Somatomedins/ (38738)
Appendix A   46 Somatomedin*.tw,kw. (2456)
Database: Ovid MEDLINE(R) Epub Ahead of   47 or/37-46 [IGF Terms] (54087)
Print, In-Process & Other Non-Indexed Citations,   48 4 and 47 (67)
Ovid MEDLINE(R) Daily and Ovid MEDLINE(R)   49 Growth Hormone/ (42705)
<1946 to Present>   50 Human Growth Hormone/ (13200)
Search Strategy:   51 Somatotropin.rn. (42)
  52 Growth Hormone*.tw,kw. (53440)
  1 Fibromyalgia/ (7608)   53 somatotropin*.tw,kw. (4018)
  2 Fibromyalgi*.tw,kw. (8857)   54 somatropin*.tw,kw. (224)
  3 fibrositis*.tw,kw. (586)   55 GH.tw,kw. (36498)
  4 or/1-3 (10300)   56 HGH.tw,kw. (4266)
   5 exp Reactive Oxygen Species/ (160522)   57 RHGH.tw,kw. (1662)
   6 reactive oxygen spec*.tw,kw. (86480)   58 “HGH(m)”.tw,kw. (2)
  7 ROS*1.tw,kw. (127059)   59 “rHGH(m)”.tw,kw. (5)
   8 active oxygen*.tw,kw. (2664)   60 or/49-59 [GH Terms] (79019)
   9 pro oxidant*.tw,kw. (4490)   61 4 and 60 (98)

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Therapeutic Advances in Musculoskeletal Disease 10(1)

  62 Transforming Growth Factor alpha/ 104 exp Growth Hormone-Releasing Hormone/


(4123) (4933)
 63 transforming growth factor alpha.tw,kw. 105 (growth hormone releasing adj (hormone*
(4016) or factor*)).tw,kw. (3374)
  64 transforming growth factor a.tw,kw. (32) 106 somatocrinin*.tw,kw. (60)
  65 tgf-alpha.tw,kw. (4097) 107 somatoliberin*.tw,kw. (17)
  66 tgf-a.tw,kw. (50) 108 hpgrf.tw,kw. (178)
  67 tgfalpha.tw,kw. (821) 109 ghrh.tw,kw. (3293)
  68 tgfa.tw,kw. (276) 110 Gonadotropin-Releasing Hormone/ (26158)
  69 (epidermal adj4 transforming growth fac- 111 gonadotropin releasing hormone*.tw,kw.
tor*).tw,kw. (1300) (12740)
  70 or/62-69 [TGF-a Terms] (7573) 112 gonadorelin*.tw,kw. (221)
  71 4 and 70 (0) 113 gonadoliberin*.tw,kw. (164)
 72 exp Transforming Growth Factor beta/ 114 gnrh.tw,kw. (19801)
(52202) 115 gn-rh.tw,kw. (380)
 73 transforming growth factor beta*.tw,kw. 116 luteinizing hormone releasing hormone*.
(44111) tw,kw. (5418)
 74 transforming growth factor b*2.tw,kw. 117 luliberin*.tw,kw. (178)
(200) 118 (lh adj2 releasing hormone*).tw,kw.
  75 tgf-beta*.tw,kw. (54851) (1853)
  76 tgf-b*2.tw,kw. (527) 119 (lhfsh adj2 releasing hormone*).tw,kw.
  77 tgfbeta*.tw,kw. (11183) (0)
  78 tgfb*2.tw,kw. (3109) 120 lh-rh.tw,kw. (3307)
 79 (platelet adj4 transforming growth fac- 121 lhrh.tw,kw. (6255)
tor*).tw,kw. (667) 122 lhfshrh.tw,kw. (3)
 80 (bone derived adj4 transforming growth 123 lfrh.tw,kw. (3)
factor*).tw,kw. (8) 124 Thyrotropin-Releasing Hormone/
  81 milk growth factor*.tw,kw. (24) (12769)
  82 Transforming Growth Factors/ (2367) 125 (thyrotropin releasing adj (hormone* or
  83 or/72-82 [TGF-b Terms] (90052) factor*)).tw,kw. (6959)
  84 4 and 83 (4) 126 thyroliberin*.tw,kw. (456)
  85 exp Growth Substances/ (707474) 127 trh.tw,kw. (11230)
  86 growth factor*.tw,kw. (316069) 128 Pituitary Hormone-Releasing Hormones/
  87 growth regulat*.tw,kw. (10005) (3114)
  88 growth substanc*.tw,kw. (508) 129 exp Thyrotropin/ (30229)
 89 “Intercellular Signaling Peptides and 130 thyrotropin*.tw,kw. (16865)
Proteins”/ (23315) 131 thyroid stimulating hormone*.tw,kw.
  90 or/85-89 [Growth sub/Animal GS Terms] (10850)
(1007586) 132 TSH.tw,kw. (28136)
  91 4 and 90 (206) 133 Adrenocorticotropic Hormone/ (48013)
  92 Pituitary-Adrenal System/ (13648) 134 (Adrenocorticotropic adj3 hormone*).
 93 Hypothalamo-Hypophyseal System/ tw,kw. (7525)
(20362) 135 ACTH.tw,kw. (36978)
  94 92 and 93 (10492) 136 exp Luteinizing Hormone/ (45646)
 95 (hypothalam* adj2 pituitar* adj2 adre- 137 Luteinizing Hormone*.tw,kw. (27538)
nal*).tw,kw. (14564) 138 interstitial cell-stimulating hormone*.
  96 HPA hormone*.tw,kw. (58) tw,kw. (100)
  97 Corticotropin-Releasing Hormone/ (11355) 139 lh.tw,kw. (50271)
  98 (corticotropin releasing adj (hormone* or 140 icsh.tw,kw. (405)
factor*)).tw,kw. (10836) 141 exp Follicle Stimulating Hormone/
  99 corticoliberin*.tw,kw. (159) (36262)
100 crf-41.tw,kw. (145) 142 Follicle Stimulating Hormone*.tw,kw.
101 crf41.tw,kw. (9) (17748)
102 CRH.tw,kw. (6220) 143 FSH.tw,kw. (32350)
103 (acth releasing adj (hormone* or factor*)) 144 Gonadotropins, Pituitary/ (6582)
.tw,kw. (51) 145 exp Testosterone/ (66499)

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D Kumbhare, S Ahmed et al.

146 testosteron*.tw,kw. (75376) 197 neuro regulator*.tw,kw. (20)


147 exp Estradiol/ (79371) 198 neuro modulator*.tw,kw. (63)
148 estradiol*.tw,kw. (75793) 199 neuro humor*.tw,kw. (258)
149 oestradiol*.tw,kw. (12797) 200 NT.tw,kw. (32894)
150 Hydrocortisone/ (67625) 201 or/190-200 [NT Terms] (118788)
151 hydrocortison*.tw,kw. (17704) 202 4 and 201 (195)
152 cortisol*.tw,kw. (54435) 203 Serotonin/ (65738)
153 epicortisol*.tw,kw. (21) 204 serotonin*.tw,kw. (89169)
154 Prolactin/ (38745) 205 5-hydroxytryptamine*.tw,kw. (20767)
155 prolactin*.tw,kw. (42404) 206 5hydroxytryptamine*.tw,kw. (4)
156 pituitary mammotropic hormone*.tw,kw. 207 5-ht.tw,kw. (35796)
(2) 208 5ht.tw,kw. (3638)
157 pituitary lactogenic hormone*.tw,kw. (33) 209 hippophaine*.tw,kw. (1)
158 prl.tw,kw. (15849) 210 enteramine*.tw,kw. (91)
159 Thyroxine/ (35677) 211 exp Dopamine/ (72455)
160 thyroxin*.tw,kw. (29628) 212 dopamine*.tw,kw. (137358)
161 lthyroxin*.tw,kw. (7) 213 hydroxytyramine*.tw,kw. (85)
162 thyrox*.tw,kw. (29650) 214 dihydroxyphenethylamine*.tw,kw. (54)
163 tyrosine*.tw,kw. (154357) 215 exp Norepinephrine/ (84410)
164 (t4 adj3 thyroid hormone*).tw,kw. (726) 216 methoxynoradrenaline*.tw,kw. (1)
165 Neurotransmitter Agents/ (26591) 217 metadrenaline*.tw,kw. (70)
166 neurohormone*.tw,kw. (3022) 218 normetadrenaline*.tw,kw. (50)
167 neuro-hormone*.tw,kw. (57) 219 Norepinephrine*.tw,kw. (54056)
168 neuroendocrine hormone*.tw,kw. (331) 220 noradrenaline*.tw,kw. (36004)
169 neuro-endocrine hormone*.tw,kw. (7) 221 noradrenalin*.tw,kw. (37562)
170 neuropeptides/ (24351) 222 Epinephrine/ (53789)
171 neuropeptide*.tw,kw. (39401) 223 epinephrine*.tw,kw. (36758)
172 neuro-peptide*.tw,kw. (64) 224 adrenalin*.tw,kw. (21615)
173 or/94-172 [HPA Hormones Terms] 225 adrenaline*.tw,kw. (18628)
(709727) 226 epifrin*.tw,kw. (3)
174 4 and 173 (408) 227 metadrenaline*.tw,kw. (70)
175 Calcitonin Gene-Related Peptide*.tw,kw. 228 metanephrine*.tw,kw. (1265)
(10352) 229 Melatonin/ (17360)
176 CGRP.tw,kw. (8801) 230 N-acetyl-5-methoxy tryptamine.tw,kw.
177 Calcitonin Gene-Related Peptide/ (19)
(10955) 231 Melatonin*.tw,kw. (20941)
178 or/175-177 [CGRP Terms] (14822) 232 Catecholamines/ (35231)
179 4 and 178 (12) 233 catecholamine*.tw,kw. (57751)
180 Substance P/ (16556) 234 sympathin*.tw,kw. (85)
181 substance p*2.tw,kw. (21651) 235 Biogenic Monoamines/ (3486)
182 “sp(1-11)”.tw,kw. (30) 236 monoamine*.tw,kw. (31317)
183 sub-p*2.tw,kw. (698) 237 gamma-Aminobutyric Acid/ (35956)
184 or/180-183 [Sub-P Terms] (24608) 238 gamma aminobutyric acid*.tw,kw.
185 4 and 184 (91) (22499)
186 (brain adj3 metabolit*).tw,kw. (2389) 239 gaba.tw,kw. (48856)
187 brain/me (134766) 240 gammalon*.tw,kw. (9)
188 or/186-187 [Brain metabolite Terms] 241 aminalon*.tw,kw. (20)
(136039) 242 4-aminobutyric acid*.tw,kw. (185)
189 4 and 188 (33) 243 4-aminobutanoic acid*.tw,kw. (32)
190 Neurotransmitter Agents/ (26591) 244 y-aminobutyric acid*.tw,kw. (48)
191 neurotransmitter*.tw,kw. (61107) 245 Glutamic Acid/ (35530)
192 neuroregulator*.tw,kw. (458) 246 glutamate.tw,kw. (92033)
193 neuromodulator*.tw,kw. (8532) 247 glutamic.tw,kw. (26711)
194 neurohumor*.tw,kw. (3776) 248 Glu.tw,kw. (26545)
195 nerve transmitter*.tw,kw. (44) 249 or/203-248 [NT Terms continued]
196 neuro transmitter*.tw,kw. (141) (620917)

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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)

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D Kumbhare, S Ahmed et al.

 74 transforming growth factor b*2.tw,kw. 117 luliberin*.tw,kw. (1)


(17) 118 (lh adj2 releasing hormone*).tw,kw. (69)
  75 tgf-beta*.tw,kw. (637) 119 (lhfsh adj2 releasing hormone*).tw,
  76 tgf-b*2.tw,kw. (51) kw. (0)
  77 tgfbeta*.tw,kw. (115) 120 lh-rh.tw,kw. (149)
  78 tgfb*2.tw,kw. (44) 121 lhrh.tw,kw. (412)
 79 (platelet adj4 transforming growth fac- 122 lhfshrh.tw,kw. (0)
tor*).tw,kw. (21) 123 lfrh.tw,kw. (0)
 80 (bone derived adj4 transforming growth 124 Thyrotropin-Releasing Hormone/ (295)
factor*).tw,kw. (0) 125 (thyrotropin releasing adj (hormone* or
  81 milk growth factor*.tw,kw. (0) factor*)).tw,kw. (264)
  82 Transforming Growth Factors/ (4) 126 thyroliberin*.tw,kw. (4)
  83 or/72-82 [TGF-b Terms] (1082) 127 trh.tw,kw. (483)
  84 4 and 83 (0) 128 Pituitary Hormone-Releasing Hormones/
  85 exp Growth Substances/ (19004) (33)
  86 growth factor*.tw,kw. (7786) 129 exp Thyrotropin/ (792)
  87 growth regulat*.tw,kw. (38) 130 thyrotropin*.tw,kw. (773)
  88 growth substanc*.tw,kw. (11) 131 thyroid stimulating hormone*.tw,kw.
 89 “Intercellular Signaling Peptides and (513)
Proteins”/ (209) 132 TSH.tw,kw. (1370)
  90 or/85-89 [Growth sub/Animal GS Terms] 133 Adrenocorticotropic Hormone/ (1247)
(26394) 134 (Adrenocorticotropic adj3 hormone*).
  91 4 and 90 (33) tw,kw. (481)
  92 Pituitary-Adrenal System/ (628) 135 ACTH.tw,kw. (1791)
  93 Hypothalamo-Hypophyseal System/ (649) 136 exp Luteinizing Hormone/ (1555)
  94 92 and 93 (544) 137 Luteinizing Hormone*.tw,kw. (1694)
 95 (hypothalam* adj2 pituitar* adj2 adre- 138 interstitial cell-stimulating hormone*.
nal*).tw,kw. (1034) tw,kw. (1)
  96 HPA hormone*.tw,kw. (6) 139 lh.tw,kw. (2679)
  97 Corticotropin-Releasing Hormone/ (225) 140 icsh.tw,kw. (3)
  98 (corticotropin releasing adj (hormone* or 141 exp Follicle Stimulating Hormone/ (1758)
factor*)).tw,kw. (294) 142 Follicle Stimulating Hormone*.tw,kw.
  99 corticoliberin*.tw,kw. (0) (1458)
100 crf-41.tw,kw. (3) 143 FSH.tw,kw. (2696)
101 crf41.tw,kw. (2) 144 Gonadotropins, Pituitary/ (76)
102 CRH.tw,kw. (277) 145 exp Testosterone/ (2259)
103 (acth releasing adj (hormone* or factor*)) 146 testosteron*.tw,kw. (4121)
.tw,kw. (6) 147 exp Estradiol/ (3568)
104 exp Growth Hormone-Releasing Hormone/ 148 estradiol*.tw,kw. (5292)
(333) 149 oestradiol*.tw,kw. (1036)
105 (growth hormone releasing adj (hormone* 150 Hydrocortisone/ (5011)
or factor*)).tw,kw. (259) 151 hydrocortison*.tw,kw. (2910)
106 somatocrinin*.tw,kw. (2) 152 cortisol*.tw,kw. (7255)
107 somatoliberin*.tw,kw. (0) 153 epicortisol*.tw,kw. (0)
108 hpgrf.tw,kw. (8) 154 Prolactin/ (1618)
109 ghrh.tw,kw. (412) 155 prolactin*.tw,kw. (2766)
110 Gonadotropin-Releasing Hormone/ (1152) 156 pituitary mammotropic hormone*.tw,
111 gonadotropin releasing hormone*.tw,kw. kw. (0)
(974) 157 pituitary lactogenic hormone*.tw,kw. (0)
112 gonadorelin*.tw,kw. (424) 158 prl.tw,kw. (852)
113 gonadoliberin*.tw,kw. (4) 159 Thyroxine/ (820)
114 gnrh.tw,kw. (2139) 160 thyroxin*.tw,kw. (1063)
115 gn-rh.tw,kw. (16) 161 lthyroxin*.tw,kw. (2)
116 luteinizing hormone releasing hormone*. 162 thyrox*.tw,kw. (1064)
tw,kw. (302) 163 tyrosine*.tw,kw. (1988)

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Therapeutic Advances in Musculoskeletal Disease 10(1)

164 (t4 adj3 thyroid hormone*).tw,kw. (32) 217 metadrenaline*.tw,kw. (2)


165 Neurotransmitter Agents/ (237) 218 normetadrenaline*.tw,kw. (2)
166 neurohormone*.tw,kw. (205) 219 Norepinephrine*.tw,kw. (3401)
167 neuro-hormone*.tw,kw. (1) 220 noradrenaline*.tw,kw. (1701)
168 neuroendocrine hormone*.tw,kw. (16) 221 noradrenalin*.tw,kw. (2271)
169 neuro-endocrine hormone*.tw,kw. (0) 222 Epinephrine/ (2877)
170 neuropeptides/ (100) 223 epinephrine*.tw,kw. (4260)
171 neuropeptide*.tw,kw. (660) 224 adrenalin*.tw,kw. (2698)
172 neuro-peptide*.tw,kw. (2) 225 adrenaline*.tw,kw. (1898)
173 or/94-172 [HPA Hormones Terms] (30462) 226 epifrin*.tw,kw. (0)
174 4 and 173 (35) 227 metadrenaline*.tw,kw. (2)
175 Calcitonin Gene-Related Peptide*.tw,kw. 228 metanephrine*.tw,kw. (42)
(256) 229 Melatonin/ (773)
176 CGRP.tw,kw. (224) 230 N-acetyl-5-methoxy tryptamine.tw,kw. (1)
177 Calcitonin Gene-Related Peptide/ (128) 231 Melatonin*.tw,kw. (1355)
178 or/175-177 [CGRP Terms] (308) 232 Catecholamines/ (980)
179 4 and 178 (2) 233 catecholamine*.tw,kw. (2798)
180 Substance P/ (166) 234 sympathin*.tw,kw. (1)
181 substance p*2.tw,kw. (395) 235 Biogenic Monoamines/ (38)
182 “sp(1-11)”.tw,kw. (0) 236 monoamine*.tw,kw. (1001)
183 sub-p*2.tw,kw. (339) 237 gamma-Aminobutyric Acid/ (916)
184 or/180-183 [Sub-P Terms] (750) 238 gamma aminobutyric acid*.tw,kw. (348)
185 4 and 184 (8) 239 gaba.tw,kw. (804)
186 (brain adj3 metabolit*).tw,kw. (89) 240 gammalon*.tw,kw. (3)
187 brain/me (88) 241 aminalon*.tw,kw. (1)
188 or/186-187 [Brain metabolite Terms] (175) 242 4-aminobutyric acid*.tw,kw. (156)
189 4 and 188 (1) 243 4-aminobutanoic acid*.tw,kw. (0)
190 Neurotransmitter Agents/ (237) 244 y-aminobutyric acid*.tw,kw. (4)
191 neurotransmitter*.tw,kw. (974) 245 Glutamic Acid/ (232)
192 neuroregulator*.tw,kw. (11) 246 glutamate.tw,kw. (1038)
193 neuromodulator*.tw,kw. (207) 247 glutamic.tw,kw. (487)
194 neurohumor*.tw,kw. (339) 248 Glu.tw,kw. (286)
195 nerve transmitter*.tw,kw. (0) 249 or/203-248 [NT Terms continued]
196 neuro transmitter*.tw,kw. (6) (26653)
197 neuro regulator*.tw,kw. (2) 250 4 and 249 (146)
198 neuro modulator*.tw,kw. (2) 251 Biomarkers/ (10511)
199 neuro humor*.tw,kw. (9) 252 biomarker*.tw,kw. (10630)
200 NT.tw,kw. (1642) 253 (bio* adj3 marker*).tw,kw. (5248)
201 or/190-200 [NT Terms] (3293) 254 (clinical adj3 marker*).tw,kw. (903)
202 4 and 201 (13) 255 (surrogate adj3 endpoint).tw,kw. (96)
203 Serotonin/ (924) 256 (surrogate adj3 end point*).tw,kw. (142)
204 serotonin*.tw,kw. (5531) 257 (surrogate adj3 marker*).tw,kw. (902)
205 5-hydroxytryptamine*.tw,kw. (694) 258 (laboratory adj3 marker*).tw,kw. (146)
206 5hydroxytryptamine*.tw,kw. (0) 259 (serum adj3 marker*).tw,kw. (1746)
207 5-ht.tw,kw. (1325) 260 or/251-259 [General Biomarker Terms]
208 5ht.tw,kw. (205) (23066)
209 hippophaine*.tw,kw. (0) 261 4 and 260 (36)
210 enteramine*.tw,kw. (0) 262 19 or 31 or 36 or 48 or 61 or 71 or 84 or
211 exp Dopamine/ (1070) 91 or 174 or 179 or 185 or 189 or 202 or
212 dopamine*.tw,kw. (5405) 250 or 261 (233)
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213 hydroxytyramine*.tw,kw. (0) 263 262 not (exp animal/ not exp humans/)
journals.sagepub.com/ 214 dihydroxyphenethylamine*.tw,kw. (1) (233)
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215 exp Norepinephrine/ (2472) 264 limit 263 to english language (205)
SAGE journals 216 methoxynoradrenaline*.tw,kw. (0) 265 limit 264 to yr=“1990 -Current” (203)

26 journals.sagepub.com/home/tab

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