The association between a history of lifetime traumatic events and pain severity physical function and affective distress in patients with chronic pai

The Association Between a History of Lifetime
Traumatic Events and Pain Severity, Physical Function,
and Affective Distress in Patients With Chronic Pain
Andrea L. Nicol,* Christine B. Sieberg,y
Daniel J. Clauw,z
Afton L. Hassett,z
Stephanie E. Moser,z
and Chad M. Brummettz
*Department of Anesthesiology, University of Kansas School of Medicine, Kansas City, Kansas.
y
Division of Pain Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, and Biobehavioral
Pediatric Pain Lab, Boston Children’s Hospital; and Department of Psychiatry, Harvard Medical School, Boston,
Massachusetts.
z
Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan.
Abstract: Evidence suggests that pain patients who report lifetime abuse experience greater psy-
chological distress, have more severe pain and other physical symptoms, and greater functional
disability. The aim of the present study was to determine the associations between a history of life-
time abuse and affective distress, fibromyalgianess (measured using the 2011 Fibromyalgia Survey),
pain severity and interference, and physical functioning. A cross-sectional analysis of 3,081 individ-
uals presenting with chronic pain was performed using validated measures and a history of abuse
was assessed via patient self-report. Multivariate logistic regression showed that individuals with
a history of abuse (n = 470; 15.25%) had greater depression, greater anxiety, worse physical func-
tioning, greater pain severity, worse pain interference, higher catastrophizing, and higher scores
on the Fibromyalgia Survey criteria (P < .001 for all comparisons). Mediation models showed that
the Fibromyalgia Survey score and affective distress independently mediate the relationship between
abuse and pain severity and physical functioning (Ps < .001). Our mediation models support a novel
biopsychosocial paradigm wherein affective distress and fibromyalgianess interact to play significant
roles in the association between abuse and pain. We posit that having a centralized pain phenotype
underlies the mediation of increased pain morbidity in individuals with a history of abuse.
Perspective: This article examines the associations between a history of lifetime abuse and affec-
tive distress, fibromyalgianess, pain severity and interference, and physical functioning in chronic
pain patients. Our findings support a novel biopsychosocial paradigm in which affective distress
and fibromyalgianess interact to play roles in the association between abuse and pain.
ª 2016 by the American Pain Society
Key words: Chronic pain, pain severity, affective distress, fibromyalgia, traumatic events.
I
t is estimated that more than 100 million Americans
live with chronic pain.11
The development and mainte-
nance of chronic pain syndromes represent a compli-
cated and dynamic interplay between psychological,
social, and biological factors that still remains incom-
pletely elucidated to date, although the role of trau-
matic events has been identified as potentially salient
with those exposed to traumatic events reporting a
Received April 14, 2016; Revised September 5, 2016; Accepted September
7, 2016.
This research was funded by the Department of Anesthesiology, Uni-
versity of Michigan Medical School. Dr. Nicol receives research funding
from the Department of Anesthesiology at University of Kansas School
of Medicine. Dr. Sieberg receives research funding from a Boston Chil-
dren’s Hospital Career Development Fellowship Award, the Sara Page
Mayo Endowment for Pediatric Pain Research and Treatment, and the
Department of Anesthesiology, Perioperative and Pain Medicine at
Boston Children’s Hospital. Dr. Hassett receives research funding for
investigator-initiated studies from Bristol-Myers Squibb. Dr. Brummett
receives research funding from the National Institutes of Health,
NIAMS R01 AR060392 and NIDA 1R01DA038261-01A1, the University
of Michigan Medical School Dean’s Office (Michigan Genomics Initia-
tive), and Neuros Medical Inc (Willoughby Hills, OH).
Dr. Hassett is a consultant for Happify, Inc, and Precision Health Eco-
nomics. Dr. Brummett discloses that the University of Michigan holds
a patent for the use of peripheral perineural dexmedetomidine alone
and in combination with local anesthetics (application number 12/
791,506; issue date: April 2, 2013; patent number 8410140). Dr. Hassett
receives research funding for investigator-initiated studies from Bristol-
Myers Squibb. Dr. Brummett receives research funding from Neuros
Medical Inc (Willoughby Hills, OH). The remaining authors have no con-
flicts of interest to declare.
Supplementary data accompanying this article are available online at
www.jpain.org and www.sciencedirect.com.
Address reprint requests to Andrea L. Nicol, MD, MSc, Anesthesiology,
University of Kansas School of Medicine, 3901 Rainbow Boulevard, MS
1034, Kansas City, KS 66160. E-mail: anicol@kumc.edu
1526-5900/$36.00
ª 2016 by the American Pain Society
http://dx.doi.org/10.1016/j.jpain.2016.09.003
1334
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Available online at www.jpain.org and www.sciencedirect.com
Downloaded from ClinicalKey.com at Salem Hospital February 17, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.

higher incidence of chronic pain.54
There are many re-
ports describing the association of sexual and physical
abuse and patients with abdominal pain,25,26,58
pelvic
pain,36,44,54,70,87,90
musculoskeletal pain,60,98
low back
pain,54,61,76
and fibromyalgia (FM).8,41,43,62,65,88,91
For
example, studies have shown that 28 to 71% of FM
patients report a history of abuse.2,42,66
Evidence
suggests that patients who report lifetime abuse
experience greater psychological distress, have more
severe physical symptoms, poorer psychological
adjustment, greater functional disability, and utilize
more health care services.3,68,86
Thus, further
understanding of the patterns of chronic pain in
survivors of abuse and trauma is important for
appropriate clinical assessment and intervention, which
in turn, should improve physical and psychological
functioning, as well as reduce disability and health care
utilization.
In adult patients with a history of abuse who present
to tertiary care centers for chronic pain symptoms, pe-
ripheral factors are likely important. However, central
nervous system (CNS) mechanisms such as diffuse hyper-
algesia/allodynia and impaired descending pain modula-
tion indicative of a strong component of centralized pain
are often playing even more prominent roles than
ongoing nociceptive input in many or even most chronic
pain patients.18,97
FM is the prototypical centralized pain
syndrome in which the pain is largely perceived to be the
result of CNS amplification of pain signals. FM is a
complex and difficult to treat painful medical condition
affecting between 2 to 4% of the population.19,56,89,95
Patients with FM and other similar centralized chronic
pain syndromes (chronic pelvic pain, irritable bowel
syndrome, migraine) tend to be female, exhibit altered
sensory and pain processing, have a family history of
chronic pain and/or psychiatric illness, and express an
array of comorbid symptoms. The traditionally
described diagnosis is primarily on the basis of
widespread pain and diffuse tenderness,96
but addi-
tional symptoms frequently include fatigue, sleep distur-
bance, anxiety, depression, various somatic complaints,
and cognitive impairment.9,77,94
In 2011, the FM Survey
Criteria were created as a way to assess the widespread
pain and comorbid symptoms associated with FM and
because of the self-report nature of the measure, it can
be used in epidemiological studies to better understand
patient characteristics and predict outcomes.13,14
Although individuals with FM have identifiable
depression (lifetime prevalence of 90% for depressive
symptoms and 62–86% for major depressive
disorder6,31
) or anxiety (lifetime prevalence 35–60% for
anxiety disorders6,27
), studies using the 2011 FM Survey
Criteria score as a continuous rather than categorical
variable have shown that this measure is only weakly
correlated with measures of anxiety and depression in
individuals who do not meet criteria for FM but have
high ‘‘subthreshold levels.13,15,45
These studies have
also shown that as the FM Survey Criteria score
increases individuals become less responsive to opioids
and to surgery intended to relieve pain, and this effect
is independent of measures of anxiety and depression.
Thus, this study is one of the first to separately
investigate the effects of the degree of FM or
centralized pain, and the effects of anxiety and
depression, on other pain outcomes.
Although there is ample evidence that traumatic
events, including abuse, are associated with affective
distress and chronic pain syndromes, there are few
studies investigating the complex associations and inter-
actions that link them. Our study sought to investigate
these relationships further and determine the associa-
tions between affective distress, including depression
and anxiety, pain severity and interference, physical
functioning, and a history of traumatic events in chronic
pain patients presenting to a tertiary care pain clinic with
a broad spectrum of pain diagnoses. Furthermore, we
aimed to explore a novel hypothesis that the continuous
FM score termed ‘‘fibromyalgianess,’’18,92
measured
using the 2011 FM Survey Criteria,93
could potentially
mediate the relationship between abuse history and af-
fective disease, pain severity, and physical functioning.
Our hypothesis was that patients with a history of life-
time trauma would present with a worse clinical pheno-
type and would describe higher levels of negative affect,
greater pain severity, and reduced physical functioning,
even when controlling for the FM Survey Criteria score.
Further, we also hypothesized that FM and affect would
serve as the mechanisms through which trauma is related
to pain and function. Thus, not only would those with
trauma have higher FM Survey Criteria scores and poorer
affect, but in turn, higher FM Survey Criteria scores and
poor affect would be associated with increased pain
and decreased function.
Methods
Study Participants
The data for this cross-sectional study were derived
from a clinical care and research initiative at the Univer-
sity of Michigan Back and Pain Center (Department of
Anesthesiology). All new patients presenting for care
complete an initial assessment packet, which includes a
questionnaire about medical comorbidities and multiple
validated self-report measures of pain, mood, and func-
tion.40
For the present study, patients aged 18 years and
older who presented to the Back and Pain Center from
November 2010 to February 2014 were included
(N = 3,081). During their initial consultation, patients
were provided a cover letter outlining the use of their
data for clinical care and research and provided the op-
portunity to not participate in research. Because the
data are collected in the context of routine clinical
care, informed consent is not required and a waiver of
informed consent is obtained. At the time of this study,
no patients had opted out of participating in the
research portion of the initiative. New patient packets
are collected at the patient’s initial visit and the data
are entered into the Assessment of Pain Outcomes Longi-
tudinal Data Capture system. The Assessment of Pain
Outcomes Longitudinal data collection and all subse-
quent analyses from this database have been approved
Nicol et al The Journal of Pain 1335

by the institutional review board (University of Michi-
gan, Ann Arbor, MI).
Measures
History of Trauma
In the new patient questionnaire packet, part of the
assessment used in this study, includes specific questions
about traumatic events. The first question asks, ‘‘Do you
have a history of physical or sexual abuse?’’ The follow-
up question then determines when the traumatic events
occurred, ‘‘If yes, did this occur when you were a.?’’ and
3 options provided, ‘‘Child (<13 years),’’ ‘‘Adolescent (13–
18 years),’’ or ‘‘Adult.’’ For this study, the primary predic-
tor of interest was considered to be a binary response on
the basis of whether or not the patient had reported a
history of lifetime abuse. Subsequent analyses investi-
gated those patients describing child or adolescent
abuse versus abuse as an adult.
Chronic Pain Diagnosis
International Classification of Diseases, Ninth Revision
(ICD-9) diagnosis codes were obtained for all patients
included in the present study. The primary pain diagnosis
was then classified into one of the following types of ma-
jor chronic pain syndromes on the basis of their primary
ICD-9 diagnosis code: 1) spine pain (including cervical,
thoracic, and lumbar spine); 2) headache and facial
pain; 3) joint pain (eg, shoulders, elbows, hip, knees);
4) extremity pain (eg, arms, legs, feet, hands); 5) neuro-
pathic pain; 6) abdominal and genitourinary pain; 7)
widespread musculoskeletal pain; 8) cancer pain; and 9)
miscellaneous pain (eg, chest, teeth, ribs).
Pain Severity and Interference
The Brief Pain Inventory (BPI) is a commonly used, well
validated self-report measure that assesses pain severity
and the interference of the pain on daily living.20
The
severity of pain is assessed using a 4-item scale that asks
about pain at its average, worst, and least right now,
and in the past week. Patients rate their pain for each
item on a scale of 0 to 10, where 0 = ‘‘No pain’’ and
10 = ‘‘Pain as bad as you can imagine.’’ A single composite
score of pain severity is then calculated as an average of
the scores for the 4 items.46
Cronbach a for the BPI pain
severity scale was .87. Pain interference is measured us-
ing a 7-item scale. Patients are asked to rate the degree
to which their pain interfered with different facets of
their daily life (general activity, mood, walking ability,
normal work, relationships with others, sleep, and enjoy-
ment of life) over the past week on a scale of 0 to 10,
where 0 = ‘‘Does not interfere’’ and 10 = ‘‘Completely in-
terferes.’’ Cronbach a for the BPI pain interference scale
was .89.
Anxiety and Depressive Symptoms
The presence of anxiety and depressive symptoms was
assessed using the Hospital Anxiety and Depression Scale
(HADS). This simple self-report tool measures psycholog-
ical distress and has been validated in general and
medical populations.99
It consists of 7 items to assess
symptoms of anxiety and 7 items to evaluate for depres-
sive symptoms. For this study, we included the anxiety
and depression subscales. Scores range from 0 to 21 for
each subscale and higher scores indicate increased levels
of depressive or anxiety symptoms. A score of 0 to 7 is
considered to be within the normal range; a score of 8
to 10 is suggestive of the presence of depression or anx-
iety; and a score of 11 or higher represents a high likeli-
hood that depression or anxiety is present. Cronbach a
for the depression subscale was .84 and a for the anxiety
subscale was .82.
Catastrophizing Phenotype
The Coping Strategies Questionnaire contains a sub-
scale for pain catastrophizing, which is a valid and reli-
able measure of this cognitive process. Scores range
from 0 to 36 with higher scores indicating higher levels
of pain catastrophizing.78
Cronbach a for the catastroph-
izing scale was .88.
Functional Status
The Patient-Reported Outcomes Measurement Infor-
mation System (PROMIS) Physical Function Short
Form-1 scale is a validated 10-item self-report measure-
ment tool used to assess physical functioning.16
Raw
scores are converted to T scores, per PROMIS guidelines,
and range from 14.1 to 61.7, with higher scores repre-
senting better physical functioning. Cronbach a for the
physical function scale was .91.
FM Survey Criteria
The Widespread Pain Index is derived from the Michi-
gan Body Map,12
a 2-dimensional mannequin checklist
that illustrates 35 potentially painful body locations
including the 19 areas comprising the 2011 FM Survey
Criteria (scores range from 0 to 19).93
Associated symp-
tom presence and severity were assessed using the Symp-
tom Severity Scale, with scores ranging from 0 to 12.93
The 2 scores are combined to create a single 0 to 31 FM
Survey Criteria score. Cut points for being termed ‘‘FM-
positive’’ have previously been described.93
In addition,
the variable can also be scored in a continuous fashion
termed ‘‘fibromyalgianess.’’18,92
Cronbach a for the FM
scale was .87.
Statistical Analysis
All analyses were conducted using Stata version 13.1
(StataCorp, College Station, TX). Patients with missing
data for the history of abuse item or those with current
abuse were excluded from the analyses. Missing data
for the validated self-report measures were handled as
described by the authors of the measures.40
Univariate
differences were evaluated between those with a history
of abuse and those without for demographic character-
istics (ie, age, gender), pain severity, FM Survey Criteria
score, affect, and physical functioning using t-tests and
c2
tests. A multivariate logistic regression was conducted
to assess independent associations between the ele-
ments of the cross-sectional pain phenotype (eg, pain
1336 The Journal of Pain Lifetime Traumatic Events and Pain

severity, depression, anxiety, catastrophizing, FM scores)
and a history of abuse.
A series of 6 multivariable linear regression models
were evaluated using the following outcomes: HADS
Depression, HADS Anxiety, PROMIS Function, BPI Pain
Severity, BPI Pain Interference, and Coping Strategies
Questionnaire Pain Catastrophizing. In each model, the
binary variable of whether patient has a history of abuse
was the primary predictor of interest. The continuous FM
Survey Criteria score was included as a covariate. To
assess potential differences between childhood/adoles-
cent abuse and adult abuse histories, univariate analyses
of the same demographic and pain phenotype variables
were conducted using t-tests and c2
tests.
Finally, to further explore the relationships between
abuse, FM Survey Criteria score, affect, and pain, 4 medi-
ation models were tested that were variations from the
general model presented in Fig 1. The general model
posits that fibromyalgianess and affect are potential me-
diators of the relationship between abuse and pain and
function. A correlation is allowed between the errors of
fibromyalgianess and affect. Rather than examining only
the effect of abuse compared with no abuse, the model
further includes 3 dummy variables created to compare
those with childhood or adolescent abuse, those with
adult abuse only, and those with childhood and adult
abuse with those with no history of abuse. Age, sex,
and marital status were included as covariates of each
mediator and outcome. The 4 model variations each
include fibromyalgianess as a mediator between abuse
and outcome, and also included: 1) depression as the af-
fective mediator and pain severity as the outcome, 2)
depression as the affective mediator and physical func-
tion as the outcome, 3) anxiety as the affective mediator
and pain severity as the outcome, and 4) anxiety as the
affective mediator and physical function as the outcome.
Full information maximum likelihood was used to
handle missing data and bootstrapped standard errors
with 50 replications were computed. Because the models
were fully saturated (ie, all possible paths were
included), no c2
-based fit statistics could be calculated.
Individual indirect effects of each single mediation
model were calculated with a Sobel test.
Results
Participants
A total of 3,459 patients were available for possible in-
clusion into the study; however, a total of 378 patients
had missing data for the history of abuse item or those
with current abuse and thus, were excluded from the an-
alyses. Patients with missing data for this item were an
average of 2.23 years older (P = .009) and had an average
of 1.45 points higher score on the catastrophizing scale
(P = .026) than those with complete data or no current
abuse. No other significant differences on any other de-
mographic or phenotypic variables were found between
those with data and those excluded.
Abuse History, Type of Chronic Pain,
Affective Distress, Pain Severity, FM
Survey Criteria Scores, and Functioning
A total of 470 (15.25%) patients had a history of abuse.
Univariate demographic and phenotypic differences be-
tween those with and without a history of abuse are pre-
sented in Table 1. Those with a history of abuse were also
older, more likely to be female, and less likely to be
Figure 1. Base mediation model predicts that the relationship between abuse and pain and function is mediated by fibromyalgia-
ness and affect. The model template posits that FM criteria survey score and affect (depression or anxiety) are potential mediators of
the relationship between abuse and pain and function. A correlation is allowed between the errors of the FM Survey Criteria score and
affect. Rather than examining only the effect of abuse compared with no abuse, the model further includes 3 dummy variables
created to compare those with childhood or adolescent abuse, those with adult abuse only, and those with childhood and adult abuse
with those with no history of abuse. Age, sex, and marital status were included as covariates of each mediator and outcome (not
shown).

married (P < .001 for all comparisons). Compared with
those with no history of abuse, those with a history of
abuse had greater depression, greater anxiety, worse
physical functioning, greater pain severity, worse pain
interference, higher levels of catastrophizing, and
higher scores on the FM Survey Criteria (P < .001 for all
comparisons). Pearson correlations were calculated to
assess the relationship between FM and depression
(r = .45, P < .001), and also FM and anxiety (r = .48,
P < .001). Collinearity diagnostics were also assessed,
and these 3 variables did not demonstrate problematic
variance inflation factors, which were all <1.70.
Diagnostic codes (ICD-9) were available for 2,880 (93%)
patients in our sample and the types of chronic pain that
for which the patients in this study presented are
described in Table 2. Spine pain was the most common
type of pain for the full group (n = 1,204 [41.8%]), in those
with a history of abuse (n = 171 [40.1%]), and in those
without a history of abuse (n = 1,033 [42%]). There were
no statistical differences in the distributions of the chronic
pain types between those with and without a history of
abuse, with the exception of neuropathic pain and wide-
spread musculoskeletal pain. Neuropathic pain had a
higher percentage of prevalence in those without a his-
tory of abuse (n = 470 [19.2%]) compared with those
with a history of abuse (n = 59 [13.9%], P = .02). In
contrast, widespread musculoskeletal pain was more
prevalent in those with a history of abuse (n = 39 [9.2%]
than without (n = 89 [3.6%], P < .001).
Results from a multivariate logistic regression model
conducted to assess the unique phenotypic differences
between those with a history of abuse and those without
are presented in Table 3. In this model, each pain, affect,
and function variable was included with history of abuse
as the outcome. Higher anxiety scores (adjusted odds ra-
tio [aOR] = 1.05, P = .015), poorer physical functioning
(aOR = .96, P = .001), less pain interference (aOR = .87,
P = .012), and higher FM Survey Criteria scores
(aOR = 1.09, P < .001) were independently associated
with history of abuse.
Univariate analysis of demographic and phenotypic
differences between those who had abuse as a child or
adolescent compared with those who only reported
abuse as an adult are presented in Table 4. No significant
differences in pain, affect, or function were observed;
however, those who experienced abuse as an adult
were more likely to be female (P = .005).
A series of 6 multivariable linear regression models
were conducted to assess the relationship between
abuse and affect, pain, and function controlling for FM
Survey Criteria score (Table 5). After controlling for FM,
significant relationships between abuse and increased
depression (P = .015), increased anxiety (P < .001),
decreased physical function (P = .008), and increased cat-
astrophizing (P = .026) were observed. In all models, FM
Survey Criteria score was significantly predictive of each
outcome (Ps < .001).
Mediation Models
Model 1: Fibromyalgianess and Depression as
Mediators of Pain Severity
Unstandardized path coefficients and model results
are presented in Fig 2. The indirect effects of each abuse
Table 1. Demographic and Phenotypic
Differences Between Those With and Without a
History of Abuse
VARIABLE
HISTORY OF ABUSE
(N = 470)
NO HISTORY OF
ABUSE (N = 2,611) P
Age 45.47 (13.05) 50.66 (15.87) <.001
Female 85.71% 54.89% <.001
Caucasian 89.08% 88.81% .864
Married 41.16% 59.33% <.001
HADS Depression 10.30 (4.40) 8.49 (4.55) <.001
HADS Anxiety 10.39 (4.44) 8.06 (4.35) <.001
PROMIS Physical
Functioning
34.05 (6.42) 36.96 (7.75) <.001
BPI Pain Severity 6.79 (1.5) 6.23 (1.86) <.001
BPI Pain
Interference
7.35 (1.9) 6.68 (2.26) <.001
Catastrophizing 19.18 (9.17) 15.45 (9.59) <.001
FM Criteria
Survey Score
14.85 (5.85) 11.01 (5.46) <.001
Meet criteria for
FM positive
56.14% 30.29% <.001
Table 2. Distribution of Chronic Pain Types Among Adult Pain Patients at a Tertiary Care Clinic
(n = 2,880)
TYPE OF Pain
FULL GROUP HISTORY OF ABUSE (N = 426) NO HISTORY OF ABUSE (N = 2,454)
PFREQUENCY % FREQUENCY % FREQUENCY %
Spine pain (neck and back) 1,204 41.8 171 40.1 1,033 42 .56
Headache/facial pain 240 8.3 40 9.4 200 8.1 .41
Joint pain (eg, knees, elbows, hip) 198 6.9 24 5.6 174 7.2 .29
Extremity pain (arms, legs, feet, hands) 210 7.3 36 8.5 174 7.2 .34
Neuropathic pain 529 18.4 59 13.9 470 19.2 .02
Abdominal and genitourinary pain 235 8.2 35 8.2 200 8.1 .96
Widespread musculoskeletal pain 128 4.4 39 9.2 89 3.6 < .001
Cancer pain 19 .6 1 .2 18 .7 .24
Miscellaneous pain (eg, chest, teeth, ribs) 117 4.1 21 4.9 96 3.9 .34

comparison group on pain severity according to FM Sur-
vey Criteria score were each statistically significant
(Ps < .001), providing evidence to support the notion
that fibromyalgianess mediates the relationship be-
tween abuse and pain severity.
The indirect effects of each abuse comparison group
on pain severity according to depression were statisti-
cally significant (child abuse only P < .001, adult abuse
only P = .001, child and adult abuse P < .001), providing
evidence to support the idea that depression mediates
the relationship between abuse and pain severity. After
accounting for the mediated effects of FM and depres-
sion, the direct effects between each abuse comparison
group and pain severity were no longer statistically sig-
nificant (child abuse only P = .875; adult abuse only
P = .653; child and adult abuse P = .521).
Model 2: Fibromyalgianess and Depression as
Mediators of Physical Function
comparison group were statistically significant
(Ps < .001), providing evidence to support our hypothesis
that fibromyalgianess mediates the relationship be-
tween abuse and physical functioning.
were statistically significant (Ps < .001), providing evi-
dence of depression as a mediator of the relationship be-
tween abuse and physical functioning. After accounting
for the mediated effects of FM Survey Criteria score and
depression, the direct effects between the adult abuse
comparison group and the combined abuse comparison
group and physical function were no longer statistically
significant (P = .105; P = .875, respectively). This finding
indicates that the relationship between abuse and phys-
ical functioning is mediated by fibromyalgianess and
depression. For the childhood abuse comparison group,
the relationship between abuse and physical function
was still statistically significant (P < .001) even after ac-
counting for mediated effects of FM and depression.
This indicates that the relationship between abuse and
physical function for those with childhood abuse may
not be fully accounted for by increased fibromyalgianess
or increased depression.
Model 3: Fibromyalgianess and Anxiety as
Mediators of Pain Severity
are presented in Fig 4. The indirect effects of
each abuse comparison group were statistically signifi-
cant (Ps < .001), providing evidence to support
Table 3. Multivariate Logistic Model Used to
Assess the Unique Phenotypic Differences
Between Those With History of Abuse and
Those Without
VARIABLE
ADJUSTED
OR
STANDARD
ERROR OR 95% CI P
HADS Depression 1.02 .02 .98–1.07 .344
HADS Anxiety 1.05 .02 1.01–1.09 .015
PROMIS Physical
Functioning
.96 .01 .94–.98 .001
BPI Pain Severity 1.04 .06 .94–1.16 .391
BPI Pain Interference .87 .05 .78–.97 .012
Catastrophizing 1.00 .01 .98–1.03 .673
FM Criteria Survey
Score
1.09 .02 1.06–1.12 <.001
Abbreviation: OR, odds ratio.
NOTE. History of abuse is the outcome. ORs are adjusted for each of the other
phenotype variables include in the model.
Table 4. Demographic and Phenotypic
Differences Between Those With Childhood/
Adolescent Abuse and Those With Adult Abuse
Only
VARIABLE
CHILD/ADOLESCENT
ABUSE (N = 375)
ADULT ABUSE ONLY
(N = 86) P
Age 45.81 (13.13) 45.23 (12.85) .704
Female 83.69% 95.35% .005
Caucasian 89.29% 89.41% .973
Married 41.46% 41.86% .946
HADS depression 10.1 (4.47) 10.34 (4.35) .647
HADS anxiety 9.93 (4.62) 10.49 (4.43) .302
PROMIS physical
functioning
33.93 (6.29) 34.19 (6.44) .732
BPI pain severity 6.8 (1.38) 6.8 (1.51) .991
BPI pain
interference
7.28 (1.91) 7.37 (1.89) .696
Catastrophizing 18.92 (9.07) 19.27 (9.1) .780
FM Criteria
Survey score
14.04 (5.35) 15.1 (5.94) .167
Meet criteria for
FM positive
58.31% 51.32% .267
Table 5. Multivariate Linear Regression Models
Predicting 6 Separate Outcomes From Abuse
and FM Survey Criteria Score to Assess the
Unique Relationship of Abuse and Each
Outcome After Controlling for FM
VARIABLE COEFFICIENT STANDARD ERROR P
HADS depression
Abuse .57 .23 .015
FM Survey Criteria score .36 .02 <.001
HADS anxiety
Abuse 1.00 .22 <.001
PROMIS physical function
Abuse À1.08 .40 .008
FM Survey Criteria score À.49 .03 <.001
BPI pain severity
Abuse .13 .09 .156
BPI pain interference
Abuse .01 .11 .905
Catastrophizing
Abuse 1.27 .57 .026

Figure 2. Model 1: Compared with patients with no abuse, the relationship between child abuse, adult abuse, and both forms of
abuse on pain severity are mediated by fibromyalgianess and depression. Unstandardized coefficients are presented. Covariances
among all exogenous variables and between FM and depression are presented. Not shown are paths from covariates age, gender,
and marital status to depression, FM, and pain severity. Compared with patients with no abuse, patients with either child abuse, adult
abuse, or both, each had significantly higher FM criteria survey scores. Further, there was a significant positive relationship between
FM criteria survey score and pain severity, indicating that those with higher FM scores had higher levels of pain severity. The indirect
effects of each abuse comparison group on pain severity through the FM criteria survey score were each statistically significant
(Ps < .001), providing evidence to support that fibromyalgianess mediates the relationship between abuse and pain severity.
Compared with patients with no abuse, patients with either child abuse, adult abuse, or both, each had significantly higher depres-
sion scores. Further, there was a significant positive relationship between depression and pain severity, indicating that those
with higher depression had higher levels of pain severity. The indirect effects of each abuse comparison group on pain severity
through depression were statistically significant (child abuse only P < .001, adult abuse only P = .001, and child and adult abuse
P < .001), providing evidence to support that depression mediates the relationship between abuse and pain severity. **P < .01,
***P < .001.
abuse on physical function are mediated by fibromyalgianess and depression. Unstandardized coefficients are presented. Covariances
among all exogenous variables and between FM and depression are presented. Not shown are paths from covariates age, gender, and
marital status to depression, FM, and physical function. Compared with patients with no abuse, patients with either child abuse, adult
abuse, or both, each had significantly higher FM criteria survey scores. Further, there was a significant negative relationship between
FM criteria survey score and physical function, indicating that those with higher FM scores had lower levels of physical functioning.
The indirect effects of each abuse comparison group on physical function through FM criteria survey score were statistically significant
(Ps < .001), providing evidence to support that FM fibromyalgianess mediates the relationship between abuse and physical func-
tioning. Compared with patients with no abuse, patients with either child abuse, adult abuse, or both, each had significantly higher
depression scores (Ps < .001). Further, there was a significant negative relationship between depression and physical function
(P < .001), indicating that those with higher depression had lower levels of physical functioning. The indirect effects of each abuse
comparison group on physical function through depression were statistically significant (Ps < .001), providing evidence to support
that depression mediates the relationship between abuse and physical functioning. ***P < .001.

abuse on pain severity are mediated by fibromyalgianess and anxiety. Unstandardized coefficients are presented. Covariances among
all exogenous variables and between FM and anxiety are presented. Not shown are paths from covariates age, gender, and marital
status to anxiety, FM, and pain severity. Compared with patients with no abuse, patients with either child abuse, adult abuse, or both,
each had significantly higher FM criteria survey scores (Ps < .001). Further, there was a significant positive relationship between FM
criteria survey score and pain severity (P < .001), indicating that those with higher FM scores had higher levels of pain severity. The
indirect effects of each abuse comparison group on pain severity through FM criteria survey score were statistically significant
(Ps < .001), providing evidence to support that fibromyalgianess mediates the relationship between abuse and pain severity.
Compared with patients with no abuse, patients with either child abuse, adult abuse, or both, each had significantly higher anxiety
scores (P < .001; P = .006; P < .001, respectively). Further, there was a significant positive relationship between anxiety and pain severity
(P < .001), indicating that those with higher anxiety had higher levels of pain severity. The indirect effects of each abuse comparison
group were statistically significant (child abuse only P < .001; adult abuse only P = .007, child and adult abuse P < .001), providing
evidence to support that anxiety mediates the relationship between abuse and pain severity. **P < .01, ***P < .001.
abuse on physical function are mediated by fibromyalgianess and anxiety. Unstandardized coefficients are presented. Covariances
among all exogenous variables and between FM and anxiety are presented. Not shown are paths from covariates age, gender, and
marital status to anxiety, FM, and physical function. Compared with patients with no abuse, patients with either child abuse, adult
abuse, or both, each had significantly higher FM criteria survey scores (Ps < .001). Further, there was a significant negative relationship
between FM criteria survey score and physical function (P < .001), indicating that those with higher FM scores had lower levels of physi-
cal functioning. The indirect effects of each abuse comparison group were statistically significant (Ps < .001), providing evidence to
support that fibromyalgianess mediates the relationship between abuse and physical functioning. Compared with patients with
no abuse, patients with either child abuse, adult abuse, or both, each had significantly higher anxiety scores (P < .001; P = .001;
P < .001, respectively). Further, there was a significant negative relationship between anxiety and physical function (P < .001), indi-
cating that those with higher anxiety had lower levels of physical functioning. The indirect effects of each abuse comparison group
were statistically significant (child abuse only P < .001; adult abuse only P = .007, child and adult abuse P < .001), providing evidence to
support that anxiety mediates the relationship between abuse and physical functioning. *P < .05, **P < .01, ***P < .001.

fibromyalgianess as a mediator of the relationship be-
tween abuse and pain severity.
were statistically significant (child abuse only P < .001;
adult abuse only P = .007, child and adult abuse
P < .001), providing evidence to support anxiety as a
mediator of the relationship between abuse and pain
severity. After accounting for the mediated effects of fi-
bromyalgianess and anxiety, the direct effects between
each abuse comparison group and pain severity were
no longer statistically significant (P = .913, P = .493,
P = .464), which again provides support for the idea
that this relationship is mediated by fibromyalgianess
and anxiety.
Model 4: Fibromyalgianess and Anxiety as
Mediators of Physical Function
comparison group were statistically significant
(Ps < .001), providing evidence to suggest that FM medi-
ates the relationship between abuse and physical func-
tioning.
were statistically significant (child abuse only P < .001;
adult abuse only P = .007, child and adult abuse
P < .001), providing evidence to support that anxiety me-
diates the relationship between abuse and physical func-
tioning. After accounting for the mediated effects of FM
and anxiety, the direct effects between the combined
childhood and adult abuse comparison group and the
adult only abuse group and physical function were no
longer statistically significant (P = .912, P = .071, respec-
tively), providing support that for these groups, the rela-
tionship between abuse and physical functioning is
mediated by FM and anxiety. For the childhood abuse
comparison group, the relationship between abuse and
physical function was still statistically significant
(P < .001) even after accounting for mediated effects of
FM and anxiety. This indicates that the relationship be-
tween abuse and physical function for those with child-
hood abuse is not fully accounted for by increased FM
or increased anxiety.
Discussion
In our study of 3,081 individuals seen in a tertiary care
setting for various pain diagnoses, 15% reported having
a history of abuse. For chronic pain patients, having a pos-
itive history of lifetime abuse appears to portend a worse
clinical phenotype than those without a history of abuse
(Tables 3–5). Furthermore, we have found evidence that
fibromyalgianess and affective distress mediate the
relationship between abuse and pain severity, as well as
abuse and physical functioning (Figs 2–5). In clinical
settings, survivors of abuse endorse more chronic pain.47
FM8
and psychiatric disorders have been found to
contribute to the relationship between abuse and
health73,74
; however, the exact relationship among these
variables has remained unclear. We believe our unique
findings may shed some light on the relationship among
these variables, because the data in this study support a
novel biopsychosocial paradigm wherein affective distress
and fibromyalgianess play significant independent roles
in mediating the association between abuse and pain.
Although the observed magnitude of the associations
between abuse history and outcome variables are quite
small when viewed independently, we have shown the
presence of complex mutual interactions and mediations
among childhood and adult abuse, affective distress
(including depression and anxiety), fibromyalgianess,
chronic pain severity, and physical functioning. The
mediation analyses we present in this report provide
evidence that depression, anxiety, and fibromyalgianess
may likely mediate the relationship between abuse and
pain severity, as well as abuse and physical functioning
(Figs 2–5). These mediation models reveal complex
interactional patterns that could not be detected by
univariate analyses alone. Thus, it can be hypothesized
that it is the dynamic interplay of these psychological and
physical variables that has more of an effect on severity
of pain and worsening of physical functioning than the
effect of a single variable.
Affect Mediates the Relationship
Between Abuse and Pain
Although a true directional relationship cannot be in-
ferred because of the cross-sectional nature of these
data, our findings are in line with previously published
work that has confirmed affective distress as a mediator
of the relationship between abuse and chronic pain. Pre-
vious reports have shown that depression and anxiety
appear to mediate the relationship between abuse his-
tory and chronic pain.48,51,54,64
Hassett et al39
showed
that a subset of adults who presented to a tertiary pain
clinic with chronic pain complaints had at least 2 times
the odds of reporting a history of sexual or child abuse
and were more likely to have widespread pain consistent
with centralized pain. Additionally, this cohort had 3
times the odds of meeting criteria for a positive diagnosis
of FM. Lampe et al54
reported significant associations be-
tween childhood physical and sexual abuse, stressful life
events and depression, and the occurrence of chronic
pain (chronic low back pain and chronic pelvic pain) in
a cohort of 105 female patients. McCarthy-Jones and Mc-
Carthy-Jones64
described indirect mediation of child-
hood sexual abuse and multiple chronic painful
conditions, including musculoskeletal pain and mi-
graines, by body mass index (BMI; 5–15% increased
odds) and anxiety/depression (25–48% increased odds).
In a study of 328 patients with FM, comorbid depression
was found to be a statistically significant mediator be-
tween childhood maltreatments and the presence of
FM.51
In this study, FM patients with comorbid depres-
sion were significantly more likely to report a history of
physical abuse, emotional abuse, emotional neglect,
and physical neglect. Not all studies have found a posi-
tive mediational relationship between abuse, affective
disease, and pain. Sachs-Ericsson and colleagues74
re-
ported that the higher rate of depression found in

survivors of childhood abuse was not the primary factor
in increase in pain reports and concluded that childhood
abuse and depression independently contribute to pain
reports.
Fibromyalgianess Mediates the
Relationship Between Abuse and Pain
and Function
In this study, we sought to investigate a novel hypoth-
esis that FM Survey Criteria score, ‘‘fibromyalgianess’’—
which is hypothesized to be a measure of the centralized
pain phenotype,18,93
may potentially mediate the
relationship between abuse and pain severity and
abuse and physical functioning. To our knowledge, this
study is the first to investigate this association and the
first to report the significant mediational role that FM
Survey Criteria score has on pain severity and physical
functioning in chronic pain patients with a history of
lifetime abuse. Furthermore, our study is the first to
find some variable indirect effects of FM Survey Criteria
score on pain outcomes in this cohort depending on
type of affective disease (depression vs anxiety) and
whether or not abuse was in childhood, adulthood, or
both. After controlling for the mediated effects of
affective disease and FM Survey Criteria score in the
models in which pain severity was the outcome of
interest, the direct effects of all types of abuse on pain
severity were no longer statistically significant, which
provides support that FM Survey Criteria score and
anxiety/depression mediate that relationship. However,
in the model in which physical functioning was the
outcome of interest and depression was the mediator,
we found that the direct relationship between
childhood abuse and physical functioning was still
statistically significant after controlling for these
mediators, which means that increased FM Survey
Criteria score and increased depression cannot fully
explain this relationship. Similarly, in the model in
which anxiety was a mediator on the outcome of
physical functioning, we found that the direct effects
for the childhood abuse and the adult abuse groups
and physical functioning were still statistically
significant after controlling for the mediators,
highlighting the notion that this relationship cannot
be completely accounted for by increased anxiety or
increased FM Survey Criteria score.
Effect of the Centralized Pain Phenotype
on Pain Morbidity in Abused Individuals
As aforementioned, this study is the first to explore the
FM Survey Criteria score, and thus fibromyalgianess, as a
mediator of the relationship between abuse and pain
outcomes in chronic pain patients reporting to a tertiary
care center for a variety of pain complaints. Interestingly,
49.6% (n = 233) of the cohort with a positive history of
abuse met the cut point for being deemed ‘‘FM-positive’’
using the 2011 FM Survey Criteria.18,93
Also consistent
with FM, or more broadly the hypothesized centralized
pain phenotype, patients with a history of abuse
reported higher levels of anxiety and depression,
increased pain severity, and worse functional status.
Our interpretation of these findings is that having a
centralized pain phenotype (fibromyalgianess)
underlies the increased pain morbidity in individuals
with a history of abuse. We recognize that the 2011
FM Survey Criteria assess for functional somatic
symptoms (including gastrointestinal complaints, mood
disturbances, and fatigue) which have been previously
associated with abuse history.2,53,66
However, the use of
the ‘‘fibromyalgianess’’ measure obtained from this
survey is a construct separate from assessing solely for
functional somatic symptoms because it provides an
aggregate measure of pain distribution and the
presence and severity of co-occurring somatic symptom
clusters and ultimately is hypothesized to be a surrogate
measure for the centralized pain phenotype.18,92
What is
unable to be ascertained from our study, because of the
cross-sectional design, and thus needs to be investigated
in well-designed longitudinal studies, is how the affec-
tive component or the FM component present tempo-
rally after abuse and whether or not they are mutually
exclusive. It is quite plausible that depression or anxiety
after abuse could potentially lead to symptoms of
chronic pain. Less likely is that pain symptoms after abuse
could lead to symptoms of depression and anxiety. Thus,
data from such a study would allow for a greater under-
standing of the natural time course and pathophysiology
of mood disorders and chronic pain syndromes after
abuse and lend to possible improved screening and early
treatment strategies for this at-risk population. Finally,
pain sensitivity measured using quantitative sensory
testing has been recently used to examine relationships
between a history of lifetime adversities/abuse and
chronic pain with findings suggestive of CNS pain ampli-
fication and reduced pain thresholds.69,81
Quantitative
sensory testing paradigms would likely be of great
importance in any future studies so that quantitative
and qualitative constructs are assessed to provide a
whole and complementary assessment of the potential
influence of centralized pain on relationships between
abuse and chronic pain.18,92
Differences in Timing of Abuse
(Childhood Vs Adult) on Pain Morbidities
The relationship between childhood physical and sex-
ual abuse and adult health problems has also been found
with adult survivors of abuse having increased health
problems and more painful symptoms, with current life
stress doubling the effect of childhood abuse on adult
health problems.75
Although psychiatric disorders are
associated with some of these symptoms, other etiologic
factors such as abuse-related alterations in brain func-
tioning that increase vulnerability to stress and decrease
immune function have also been implicated.28
Adult sur-
vivors of childhood abuse are also more likely to have
cognitions and beliefs that amplify health problems.63,75
However, it is unclear the role of childhood and adult-
reported abuse have on emotional functioning and
pain and health outcomes, which was a focus of the pre-
sent study.

Neuroendocrine and Neurobiological
Changes Associated With Abuse
There is increasing evidence to suggest that exposure
to stress, abuse, or traumatic events during development
can result in a broad range of lasting effects on neuro-
physiology. An altered hypothalamic-pituitary-adrenal
system has been reported as a neurobiological sequela
of early life stress.35,50,83,85
A large body of research
suggests that children exposed to abuse have diurnal
cortisol patterns that are different from the cortisol
patterns exhibited by their nonmaltreated peers.34
Spe-
cifically, children exposed to abuse tend to exhibit low
cortisol reactivity to stress even when they exhibit intense
behavioral distress and negative emotionality.33,37
With
regard to diurnal cortisol patterns, children who are
abused tend to exhibit less day to day variation in
cortisol levels compared with their nonmaltreated
counterparts.80
Specifically, these biological data suggest
that the stress system of children exposed to abuse may
be reregulated to have little internal control (blunted
cortisol response to stress system activity). Without this
control, maltreated children are more likely to exhibit un-
differentiated, low to extinguish, and maladaptive
‘‘fight, flight, or freeze’’ reactions in response to novel
stressors, which can have implications on the developing
brain when neuronal plasticity is greatest. Even if the
traumatic experience(s) occurred only in childhood, it
has been reported that this neuroendocrine dysregula-
tion can persist into adulthood.91
Changes in neurotrans-
mitter systems, including the corticotrophin-releasing
hormone circuits can occur as well.1,57
Pain sensitivity, processing, and circuitry can potentially
also be altered after early life stressors or noxious insult,
and these alterations can persist into adulthood.22,29,59
In
rat models, neonatal noxious insult or non-noxious stress
can increase theduration and magnitudeof nociceptive re-
sponsivity in adulthood.7,32,71,72
Electrophysiologic and
anatomic studies identified persistent alterations in CNS
nociceptive mechanisms resulting from neonatal pain
that likely underlies these pain behavioral effects,
including increased density and distribution of
nociceptive afferents to the spinal cord and
hyperexcitability of dorsal horn neurons at rest and in
response to non-noxious and painful stimuli.7,72,79
Brain
imaging studies have shown a reduced hippocampal
volume in adults who reported childhood stress10,21
and a
recent study has reported that a significantly smaller
amygdala volume and reduced cortical thickness in the
rostral anterior cingulate cortex exists in adolescents with
a history of a traumatic event.49
Genetic and Epigenetic Changes
Associated With Pain Morbidity After
Abuse
Genetic and epigenetic mechanisms may also play a
role in the development and maintenance of pain syn-
dromes after trauma or abuse. Several individual gene
mutations have been identified that have profound ef-
fects on pain phenotypes, including in the sodium chan-
nel NaV 1.7; which is encoded by the SCN9A gene,
guanosine triphosphate cyclohydrolase 1, and catechol-
O-methyl transferase.23,24,55,84
How genes such as these
manifest phenotypically in differing environments,
including that of a traumatic life event or abuse model,
is an important area of future investigation.
Strengths and Limitations
Although this study offers several notable strengths
including the large sample size, validated self-reported
patient outcomes, and sophisticated analysis plan, the
current study must be viewed in light of its limitations.
A major limitation of our study is the cross-sectional na-
ture, which precludes inferences and causal relation-
ships. Moreover, the associations we presented may not
be valid for every type of chronic pain syndrome; howev-
er, there is some evidence that specific pain syndromes
such as headache52,82
and neuropathic pain17
are specif-
ically associated with a history of traumatic events.
Additionally, the assessment of abuse relied on a single
self-report item instead of a validated and more granular
measure, such as the Childhood Traumatic Events Scale or
Recent Traumatic Events Scales.67
These other assessment
methods would have provided additional information
about the different types, extent, and effect of the
abuse. Furthermore, interpretation of these results is
constrained by the use of a retrospective report of abuse,
which has methodologic limitations such as respondents
having difficulty with accurate recall in past events or
providing socially desirable responses. The lower rate
of reported abuse (15%) observed in our cohort
compared with previously published findings suggest
that abuse history was likely under-reported in this study
and thus, may have had an effect on the current findings.
We also recognize that pain outcomes may differ on the
basis of the cumulative number and type of traumatic
events, which we were not able to ascertain with our
measure. Under-reporting of abuse may possibly be
because of the self-report nature and wording of the
query of abuse question. Also, slightly more than 10%
of our available cohort had missing data for the item
of abuse and thus outcomes data for these patients could
not be included in the final cohort. Future studies should
further explore the role of abuse, neglect, and chronic
stressors as well as their perceived effect on pain and
health outcomes. As with most populations of pain pa-
tients, the cohort was predominantly female. The per-
centage of the abuse cohort that is female was 85%,
which is almost identical to the percentage reported in
the study by Kosseva et al.51
Few studies have investi-
gated the effect of sex difference on abuse and chronic
pain. Men have been reported to be less likely than
women to discuss abuse on the basis of lower frequency
of being asked and lower spontaneous reporting. In
their study, Hart-Johnson and Green posited that men
with psychological impairment from abuse may be
more likely to reinterpret their affective pain through
physical manifestations.38
In addition, there was very lit-
tle racial diversity; hence differences in outcomes accord-
ing to race could not be assessed. Because there are
reliable differences in pain responses as a function of

sex and race/ethnic backgrounds, further research
should focus on constructing samples in which similar
numbers of male and female participants as well as pa-
tients with different races/ethnicities are included.
Certain physiologic variables, such as BMI, were not as-
sessed in the present study. Previous data from other
groups have revealed that controlling for BMI eliminates
significant differences in self-report measures of osteoar-
thritis pain as a function of ethnicity; however, control-
ling for BMI rarely influences ethnic group differences
in quantitative sensory testing responses for this same
population.4,5,30
In future studies, it would be useful to
determine if these relationships are seen in other
chronic pain syndromes, such as FM. Last, the data are
from a quaternary care medical center and may not be
generalizable to other populations.
Conclusions
The current study shows that individuals with chronic
pain and a history of lifetime abuse have worse affective
distress, pain severity, and physical functioning
compared with individuals without a history of abuse.
Furthermore, the results from our mediation analyses
support a novel biopsychosocial paradigm in which af-
fective distress and increased CNS pain amplification
can be triggered by trauma (as suggested by animal
and human studies) and these constructs play indepen-
dently significant roles in the association between abuse
and pain. Results from this study highlight the impor-
tance of screening for childhood abuse, as well as
instance of ongoing abuse and affective distress. Patients
with comorbid abuse and chronic pain require an inte-
grative approach to treatment that addresses their phys-
ical health complaints and psychological distress.
Additional longitudinal and epidemiologic research is
needed to better understand the temporal relationships
between and natural progression of affective distress
and chronic pain after abuse so that clinicians can effec-
tively screen for these conditions and provide early and
targeted treatment therapies.
Supplementary Data
Supplementary data related to this article can be
found online at http://dx.doi.org/10.1016/j.jpain.2016.
09.003.
References
1. Adler GK, Kinsley BT, Hurwitz S, Mossey CJ,
Goldenberg DL: Reduced hypothalamic-pituitary and sym-
pathoadrenal responses to hypoglycemia in women with fi-
bromyalgia syndrome. Am J Med 106:534-543, 1999
2. Afari N, Ahumada SM, Wright LJ, Mostoufi S, Golnari G,
Reis V, Cuneo JG: Psychological trauma and functional so-
matic syndromes: A systematic review and meta-analysis.
Psychosom Med 76:2-11, 2014
3. Alexander RW, Bradley LA, Alarcon GS, Triana-
Alexander M, Aaron LA, Alberts KR, Martin MY,
Stewart KE: Sexual and physical abuse in women with fibro-
myalgia: Association with outpatient health care utilization
and pain medication usage. Arthritis Care Res 11:102-115,
1998
4. Allen KD, Helmick CG, Schwartz TA, DeVellis RF,
Renner JB, Jordan JM: Racial differences in self-reported
pain and function among individuals with radiographic
hip and knee osteoarthritis: The Johnston County Osteo-
arthritis Project. Osteoarthritis Cartilage 17:1132-1136,
2009
5. Allen KD, Oddone EZ, Coffman CJ, Keefe FJ, Lindquist JH,
Bosworth HB: Racial differences in osteoarthritis pain and
function: Potential explanatory factors. Osteoarthritis Carti-
lage 18:160-167, 2010
6. Arnold LM, Hudson JI, Keck PE, Auchenbach MB,
Javaras KN, Hess EV: Comorbidity of fibromyalgia and psy-
chiatric disorders. J Clin Psychiatry 67:1219-1225, 2006
7. Beggs S, Currie G, Salter MW, Fitzgerald M, Walker SM:
Priming of adult pain responses by neonatal pain experi-
ence: Maintenance by central neuroimmune activity. Brain
135:404-417, 2012
8. Boisset-Pioro MH, Esdaile JM, Fitzcharles MA: Sexual and
physical abuse in women with fibromyalgia syndrome.
Arthritis Rheum 38:235-241, 1995
9. Bradley LA: Pathophysiologic mechanisms of fibromyal-
gia and its related disorders. J Clin Psychiatry 69(Suppl 2):
6-13, 2008
10. Bremner JD, Randall P, Vermetten E, Staib L, Bronen RA,
Mazure C, Capelli S, McCarthy G, Innis RB, Charney DS: Mag-
netic resonance imaging-based measurement of hippocam-
pal volume in posttraumatic stress disorder related to
childhood physical and sexual abuse–a preliminary report.
Biol Psychiatry 41:23-32, 1997
11. Brown RT, Zuelsdorff M, Fleming M: Adverse effects and
cognitive function among primary care patients taking opi-
oids for chronic nonmalignant pain. J Opioid Manag 2:
137-146, 2006
12. Brummett CM, Bakshi RR, Goesling J, Leung D, Moser SE,
Zollars JW, Williams DA, Clauw DJ, Hassett AL: Preliminary
validation of the Michigan Body Map (MBM). Pain 157:
1205-1212, 2016
13. Brummett CM, Goesling J, Tsodikov A, Meraj TS,
Wasserman RA, Clauw DJ, Hassett AL: Prevalence of the fi-
bromyalgia phenotype in patients with spine pain present-
ing to a tertiary care pain clinic and the potential
treatment implications. Arthritis Rheum 65:3285-3292, 2013
14. Brummett CM, Janda AM, Schueller CM, Tsodikov A,
Morris M, Williams DA, Clauw DJ: Survey criteria for fibromy-
algia independently predict increased postoperative opioid
consumption after lower-extremity joint arthroplasty: A
prospective, observational cohort study. Anesthesiology
119:1434-1443, 2013
15. Brummett CM, Urquhart AG, Hassett AL, Tsodikov A,
Hallstrom BR, Wood NI, Williams DA, Clauw DJ: Characteris-
tics of fibromyalgia independently predict poorer long-term
analgesic outcomes following total knee and hip arthro-
plasty. Arthritis Rheumatol 67:1386-1394, 2015
16. Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S,
Amtmann D, Bode R, Buysse D, Choi S, Cook K, Devellis R,
DeWalt D, Fries JF, Gershon R, Hahn EA, Lai JS, Pilkonis P,
Revicki D, Rose M, Weinfurt K, Hays R, PROMIS Cooperative

Group: The Patient-Reported Outcomes Measurement In-
formation System (PROMIS) developed and tested its first
wave of adult self-reported health outcome item banks:
2005-2008. J Clin Epidemiol 63:1179-1194, 2010
17. Ciccone DS, Bandilla EB, Wu W: Psychological dysfunc-
tion in patients with reflex sympathetic dystrophy. Pain 71:
323-333, 1997
18. Clauw DJ: Fibromyalgia: A clinical review. JAMA 311:
1547-1555, 2014
19. Clauw DJ, Crofford LJ: Chronic widespread pain and fi-
bromyalgia: What we know, and what we need to know.
Best Pract Res Clin Rheumatol 17:685-701, 2003
20. Cleeland CS, Ryan KM: Pain assessment: Global use of
the Brief Pain Inventory. Ann Acad Med Singapore 23:
129-138, 1994
21. Dannlowski U, Stuhrmann A, Beutelmann V,
Zwanzger P, Lenzen T, Grotegerd D, Domschke K,
Hohoff C, Ohrmann P, Bauer J, Lindner C, Postert C,
Konrad C, Arolt V, Heindel W, Suslow T, Kugel H: Limbic
scars: Long-term consequences of childhood maltreatment
revealed by functional and structural magnetic resonance
imaging. Biol Psychiatry 71:286-293, 2012
22. Davidson RJ, McEwen BS: Social influences on neuro-
plasticity: Stress and interventions to promote well-being.
Nat Neurosci 15:689-695, 2012
23. Diatchenko L, Nackley AG, Slade GD, Bhalang K, Belfer I,
Max MB, Goldman D, Maixner W: Catechol-O-methyltrans-
ferase gene polymorphisms are associated with multiple
pain-evoking stimuli. Pain 125:216-224, 2006
24. Drenth JP, Waxman SG: Mutations in sodium-channel
gene SCN9A cause a spectrum of human genetic pain disor-
ders. J Clin Invest 117:3603-3609, 2007
25. Drossman DA, Leserman J, Hu JB: Gastrointestinal diag-
nosis, abuse history, and effects on health status. Gastroen-
terology 111:1159-1161, 1996
26. Drossman DA, Leserman J, Nachman G, Li ZM, Gluck H,
Toomey TC, Mitchell CM: Sexual and physical abuse in
women with functional or organic gastrointestinal disor-
ders. Ann Intern Med 113:828-833, 1990
27. Epstein SA, Kay G, Clauw D, Heaton R, Klein D, Krupp L,
Kuck J, Leslie V, Masur D, Wagner M, Waid R, Zisook S: Psy-
chiatric disorders in patients with fibromyalgia. A multi-
center investigation. Psychosomatics 40:57-63, 1999
28. Fagundes CP, Glaser R, Kiecolt-Glaser JK: Stressful early
life experiences and immune dysregulation across the life-
span. Brain Behav Immun 27:8-12, 2013
29. Fitzgerald M: The development of nociceptive circuits.
Nat Rev Neurosci 6:507-520, 2005
30. Goode AP, Shi XA, Gracely RH, Renner JB, Jordan JM: As-
sociations between pressure-pain threshold, symptoms, and
radiographic knee and hip osteoarthritis. Arthritis Care Res
66:1513-1519, 2014
31. Gracely RH, Ceko M, Bushnell MC: Fibromyalgia and
depression. Pain Res Treat 486590:2012, 2012
32. Green PG, Chen X, Alvarez P, Ferrari LF, Levine JD: Early-
life stress produces muscle hyperalgesia and nociceptor
sensitization in the adult rat. Pain 152:2549-2556, 2011
33. Gunnar MR, Cheatham CL: Brain and behavior interface:
Stress and the developing brain. Infant Ment Health J 24:
195-211, 2003
34. Gunnar MR, Donzella B: Social regulation of the cortisol
levels in early human development. Psychoneuroendocri-
nology 27:199-220, 2002
35. Gunnar MR, Quevedo KM: Early care experiences and
HPA axis regulation in children: A mechanism for later
trauma vulnerability. Prog Brain Res 167:137-149, 2008
36. Harrop-Griffiths J, Katon W, Walker E, Holm L, Russo J,
Hickok L: The association between chronic pelvic pain, psy-
chiatric diagnoses, and childhood sexual abuse. Obstet Gy-
necol 71:589-594, 1988
37. Hart J, Gunnar M, Cicchetti D: Salivary cortisol in mal-
treated children: Evidence of relations between neuroendo-
crine activity and social competence. Dev Psychopathol 7:
11-26, 1995
38. Hart-Johnson T, Green CR: The impact of sexual or phys-
ical abuse history on pain-related outcomes among blacks
and whites with chronic pain: Gender influence. Pain Med
13:229-242, 2012
39. Hassett AL, Hilliard PE, Goesling J, Clauw DJ, Harte SE,
Brummett CM: Reports of chronic pain in childhood and
adolescence among patients at a tertiary care pain clinic. J
Pain 14:1390-1397, 2013
40. Hassett AL, Wasserman R, Goesling J, Rakovitis K,
Shi B, Brummett CM: Longitudinal assessment of pain
outcomes in the clinical setting: development of the
‘‘APOLO’’ electronic data capture system. Reg Anesth
Pain Med 37:398-402, 2012
41. Hauser W, Galek A, Erbsloh-Moller B, Kollner V, Kuhn-
Becker H, Langhorst J, Petermann F, Prothmann U,
Winkelmann A, Schmutzer G, Brahler E, Glaesmer H: Post-
traumatic stress disorder in fibromyalgia syndrome: Preva-
lence, temporal relationship between posttraumatic stress
and fibromyalgia symptoms, and impact on clinical
outcome. Pain 154:1216-1223, 2013
42. Hauser W, Kosseva M, Uceyler N, Klose P, Sommer C:
Emotional, physical, and sexual abuse in fibromyalgia syn-
drome: A systematic review with meta-analysis. Arthritis
Care Res 63:808-820, 2011
43. Haviland MG, Morton KR, Oda K, Fraser GE: Traumatic
experiences, major life stressors, and self-reporting a
physician-given fibromyalgia diagnosis. Psychiatry Res 177:
335-341, 2010
44. Heim C, Ehlert U, Hanker JP, Hellhammer DH: Abuse-
related posttraumatic stress disorder and alterations of the
hypothalamic-pituitary-adrenal axis in women with chronic
pelvic pain. Psychosom Med 60:309-318, 1998
45. Janda AM, As-Sanie S, Rajala B, Tsodikov A, Moser SE,
Clauw DJ: Brummett Fibromyalgia Survey Criteria are associ-
ated with increased postoperative opioid consumption in
women undergoing hysterectomy. Anesthesiology 122:
1103-1111, 2015
46. Jensen MP, Turner LR, Turner JA, Romano JM: The use of
multiple-item scales for pain intensity measurement in
chronic pain patients. Pain 67:35-40, 1996
47. Kendall-Tackett K: Chronic pain: The next frontier in
child maltreatment research. Child Abuse Negl 25:
997-1000, 2001
48. Koopman C, Ismailji T, Palesh O, Gore-Felton C,
Narayanan A, Saltzman KM, Holmes D, McGarvey EL: Rela-
tionships of depression to child and adult abuse and bodily
pain among women who have experienced intimate partner
violence. J Interpers Violence 22:438-455, 2007

49. Korgaonkar MS, Antees C, Williams LM, Gatt JM,
Bryant RA, Cohen R, Paul R, O’Hara R, Grieve SM: Early expo-
sure to traumatic stressors impairs emotional brain circuitry.
PLoS One 8:e75524, 2013
50. Korosi A, Baram TZ: Plasticity of the stress response early
in life: Mechanisms and significance. Dev Psychobiol 52:
661-670, 2010
51. Kosseva M, Schild S, Wilhelm-Schwenk R, Biewer W,
Hauser W: Comorbid depression mediates the association
of childhood/adolescent maltreatment and fibromyalgia
syndrome. A study with patients from different clinical set-
tings [in German]. Schmerz 24:474-484, 2010
52. Kucukgoncu S, Yildirim Ornek F, Cabalar M, Bestepe E,
Yayla V: Childhood trauma and dissociation in tertiary care
patients with migraine and tension type headache: A
controlled study. J Psychosom Res 77:40-44, 2014
53. Kugler BB, Bloom M, Kaercher LB, Truax TV, Storch EA:
Somatic symptoms in traumatized children and adolescents.
Child Psychiatry Hum Dev 43:661-673, 2012
54. Lampe A, Doering S, Rumpold G, Solder E, Krismer M,
Kantner-Rumplmair W, Schubert C, Sollner W: Chronic pain
syndromes and their relation to childhood abuse and stress-
ful life events. J Psychosom Res 54:361-367, 2003
55. Latremoliere A, Costigan M: GCH1, BH4 and pain. Curr
Pharm Biotechnol 12:1728-1741, 2011
56. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H,
Deyo RA, Gabriel S, Hirsch R, Hochberg MC, Hunder GG,
Jordan JM, Katz JN, Kremers HM, Wolfe F, National Arthritis
Data Workgroup: Estimates of the prevalence of arthritis
and other rheumatic conditions in the United States. Part
II. Arthritis Rheum 58:26-35, 2008
57. Lentjes EG, Griep EN, Boersma JW, Romijn FP, de
Kloet ER: Glucocorticoid receptors, fibromyalgia and low
back pain. Psychoneuroendocrinology 22:603-614, 1997
58. Leserman J, Drossman DA, Li Z, Toomey TC, Nachman G,
Glogau L: Sexual and physical abuse history in gastroenter-
ology practice: How types of abuse impact health status. Psy-
chosom Med 58:4-15, 1996
59. Lidow MS: Long-term effects of neonatal pain on noci-
ceptive systems. Pain 99:377-383, 2002
60. Linton SJ: A population-based study of the relationship
between sexual abuse and back pain: Establishing a link.
Pain 73:47-53, 1997
61. Linton SJ, Larden M, Gillow AM: Sexual abuse and
chronic musculoskeletal pain: Prevalence and psychological
factors. Clin J Pain 12:215-221, 1996
62. Low LA, Schweinhardt P: Early life adversity as a risk fac-
tor for fibromyalgia in later life. Pain Res Treat 140832:2012,
2012
63. Lupien SJ, McEwen BS, Gunnar MR, Heim C: Effects of
stress throughout the lifespan on the brain, behaviour and
cognition. Nat Rev Neurosci 10:434-445, 2009
64. McCarthy-Jones S, McCarthy-Jones R: Body mass index
and anxiety/depression as mediators of the effects of child
sexual and physical abuse on physical health disorders in
women. Child Abuse Negl 38:2007-2020, 2014
65. Nicolson NA, Davis MC, Kruszewski D, Zautra AJ:
Childhood maltreatment and diurnal cortisol patterns in
women with chronic pain. Psychosom Med 72:471-480,
2010
66. Paras ML, Murad MH, Chen LP, Goranson EN, Sattler AL,
Colbenson KM, Elamin MB, Seime RJ, Prokop LJ,
Zirakzadeh A: Sexual abuse and lifetime diagnosis of so-
matic disorders: a systematic review and meta-analysis.
JAMA 302:550-561, 2009
67. Pennebaker JW, Susman JR: Disclosure of traumas and
psychosomatic processes. Soc Sci Med 26:327-332, 1988
68. Peres JF, Goncalves AL, Peres MF: Psychological trauma in
chronic pain: Implications of PTSD for fibromyalgia and
headache disorders. Curr Pain Headache Rep 13:350-357,
2009
69. Pieritz K, Rief W, Euteneuer F: Childhood adversities and
laboratory pain perception. Neuropsychiatr Dis Treat 11:
2109-2116, 2015
70. Rapkin AJ, Kames LD, Darke LL, Stampler FM,
Naliboff BD: History of physical and sexual abuse in women
with chronic pelvic pain. Obstet Gynecol 76:92-96, 1990
71. Ren K, Anseloni V, Zou SP, Wade EB, Novikova SI,
Ennis M, Traub RJ, Gold MS, Dubner R, Lidow MS: Character-
ization of basal and re-inflammation-associated long-term
alteration in pain responsivity following short-lasting
neonatal local inflammatory insult. Pain 110:588-596, 2004
72. Ruda MA, Ling QD, Hohmann AG, Peng YB, Tachibana T:
Altered nociceptive neuronal circuits after neonatal periph-
eral inflammation. Science 289:628-631, 2000
73. Sachs-Ericsson N, Blazer D, Plant EA, Arnow B: Childhood
sexual and physical abuse and the 1-year prevalence of
medical problems in the National Comorbidity Survey.
Health Psychol 24:32-40, 2005
74. Sachs-Ericsson N, Cromer K, Hernandez A, Kendall-
Tackett K: A review of childhood abuse, health, and pain-
related problems: The role of psychiatric disorders and
current life stress. J Trauma Dissociation 10:170-188, 2009
75. Sachs-Ericsson N, Kendall-Tackett K, Hernandez A: Child-
hood abuse, chronic pain, and depression in the National
Comorbidity Survey. Child Abuse Negl 31:531-547, 2007
76. Schofferman J, Anderson D, Hines R, Smith G, Keane G:
Childhood psychological trauma and chronic refractory
low-back pain. Clin J Pain 9:260-265, 1993
77. Schweinhardt P, Sauro KM, Bushnell MC: Fibromyalgia: a
disorder of the brain? Neuroscientist 14:415-421, 2008
78. Swartzman LC, Gwadry FG, Shapiro AP, Teasell RW: The
factor structure of the Coping Strategies Questionnaire.
Pain 57:311-316, 1994
79. Tachibana T, Ling QD, Ruda MA: Increased Fos induction
in adult rats that experienced neonatal peripheral inflam-
mation. Neuroreport 12:925-927, 2001
80. Tarullo AR, Gunnar MR: Childhood maltreatment and
the developing HPA-axis. Horm Behav 50:632-639, 2006
81. Tesarz J, Wolfgang E, Treede RD, Gerhardt A: Altered
pressure pain thresholds and increased wind-up in adult
chronic back pain patients with a history of childhood
maltreatment: A quantitative sensory testing study. Pain
157:1799-1809, 2016
82. Tietjen GE, Brandes JL, Peterlin BL, Eloff A, Dafer RM,
Stein MR, Drexler E, Martin VT, Hutchinson S, Aurora SK,
Recober A, Herial NA, Utley C, White L, Khuder SA: Child-
hood maltreatment and migraine (part II). Emotional abuse
as a risk factor for headache chronification. Headache 50:
32-41, 2010

83. Tyrka AR, Wier L, Price LH, Ross N, Anderson GM,
Wilkinson CW, Carpenter LL: Childhood parental loss and
adult hypothalamic-pituitary-adrenal function. Biol Psychia-
try 63:1147-1154, 2008
84. van Meurs JB, Uitterlinden AG, Stolk L, Kerkhof HJ,
Hofman A, Pols HA, Bierma-Zeinstra SM: A functional poly-
morphism in the catechol-O-methyltransferase gene is asso-
ciated with osteoarthritis-related pain. Arthritis Rheum 60:
628-629, 2009
85. Videlock EJ, Adeyemo M, Licudine A, Hirano M,
Ohning G, Mayer M, Mayer EA, Chang L: Childhood trauma
is associated with hypothalamic-pituitary-adrenal axis
responsiveness in irritable bowel syndrome. Gastroenter-
ology 137:1954-1962, 2009
86. Walen HR, Oliver K, Groessl E, Cronan TA,
Rodriguez VM: Traumatic events, health outcomes, and
healthcare use in patients with fibromyalgia. J Musculoske-
let Pain 9:13-38, 2001
87. Walker E, Katon W, Harrop-Griffiths J, Holm L, Russo J,
Hickok LR: Relationship of chronic pelvic pain to psychiatric
diagnoses and childhood sexual abuse. Am J Psychiatry 145:
75-80, 1988
88. Walker EA, Keegan D, Gardner G, Sullivan M,
Bernstein D, Katon WJ: Psychosocial factors in fibromyalgia
compared with rheumatoid arthritis: II. Sexual, physical,
and emotional abuse and neglect. Psychosom Med 59:
572-577, 1997
89. Wallace DJ: The fibromyalgia syndrome. Ann Med 29:
9-21, 1997
90. Walling MK, Reiter RC, O’Hara MW, Milburn AK, Lilly G,
Vincent SD: Abuse history and chronic pain in women: I.
Prevalences of sexual abuse and physical abuse. Obstet Gy-
necol 84:193-199, 1994
91. Weissbecker I, Floyd A, Dedert E, Salmon P, Sephton S:
Childhood trauma and diurnal cortisol disruption in fibro-
myalgia syndrome. Psychoneuroendocrinology 31:312-324,
2006
92. Wolfe F: Fibromyalgianess. Arthritis Rheum 61:715-716,
2009
93. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL,
Hauser W, Katz RS, Mease P, Russell AS, Russell IJ,
Winfield JB: Fibromyalgia criteria and severity scales for clin-
ical and epidemiological studies: A modification of the ACR
Preliminary Diagnostic Criteria for Fibromyalgia. J Rheuma-
tol 38:1113-1122, 2011
94. Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL,
Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB,
Yunus MB: The American College of Rheumatology prelimi-
nary diagnostic criteria for fibromyalgia and measurement
of symptom severity. Arthritis Care Res 62:600-610, 2010
95. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L: The
prevalence and characteristics of fibromyalgia in the gen-
eral population. Arthritis Rheum 38:19-28, 1995
96. Wolfe F, Smythe HA, Yunus MB, Bennett RM,
Bombardier C, Goldenberg DL, Tugwell P, Campbell SM,
Abeles M, Clark P, Fam AG, Farber SJ, Fiechtner JJ,
Franklin CM, Gatter RA, Hamaty D, Lessard J,
Lichtbroun AS, Masi AT, Mccain GA, Reynolds WJ,
Romano TJ, Russell IJ, Sheon RP: The American College of
Rheumatology 1990 criteria for the classification of fibromy-
algia. Report of the Multicenter Criteria Committee.
Arthritis Rheum 33:160-172, 1990
97. Woolf CJ: Central sensitization: Implications for the
diagnosis and treatment of pain. Pain 152(3 Suppl):S2-S15,
2011
98. Wurtele SK, Kaplan GM, Keairnes M: Childhood sexual
abuse among chronic pain patients. Clin J Pain 6:110-113,
1990
99. Zigmond AS, Snaith RP: The Hospital Anxiety and
Depression Scale. Acta Psychiatr Scand 67:361-370, 1983

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