Contribution of Pain Catastrophizing to Race Group Differences in Pain and Pain-Related Brain Responses in Older Adults With Knee Osteoarthritis (OA)
Phase: NA
Conditions: Osteo Arthritis Knee
Sponsor: University of Florida

Protocol #:  201802819 
 
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Cover Letter 
 
 
Title of the study: Contribution of Pain Catastrophizing to Race Group Differences in Pain and 
Pain-Related Brain Responses in Older Adults With Knee Osteoarthritis (OA) 
 
NCT#: 03836586 
 
Document Date: 3/30/2022 
 
 
 

Protocol #:  201802819 
 
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IRB version:  3/9/2004 
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Protocol 
1. Project Title:  
Contribution of Pain Catastrophizing to Race Group Differences in Pain 
and Pain-Related Brain Responses in Older Adults with Knee OA. [Study of 
Pain Catastrophizing] (SPAC) 
2. Investigator(s):   
Ellen L. Terry, Ph.D. (PI) 
 
 
 
 
Roger B. Fillingim (Primary Mentor) 
 
 
 
 
 
 
 
 
 
3. Abstract: 
 
Previous research demonstrates that non-Hispanic blacks (NHB) with osteoarthritis (OA) 
experience more frequent and severe clinical pain, greater disability and show a quantitative 
sensory testing (QST) profile suggesting impaired pain inhibition and enhanced generalized pain 
facilitation compared to their non-Hispanic white (NHW) counterparts. In addition, previous 
findings demonstrated higher pain catastrophizing (a tendency to negatively evaluate one’s ability 
to cope with pain and to respond to anticipated or actual pain in a heightened negative cognitive 
and emotional manner) among NHBs compared to NHWs. While multiple factors inevitably 
contribute, race group differences in cognitive and affective processes (e.g. catastrophizing), 
represent potentially important determinants of greater clinical pain among NHBs, perhaps by 
altering central pain processing. Despite its pervasive negative effects, no neuroimaging study to 
date has experimentally manipulated pain catastrophizing and measured cerebral activity during 
experimentally-induced pain to determine the neural mechanisms whereby catastrophizing 
impacts pain responses. Moreover, the extent to which the influence of pain catastrophizing on 
these central pathways contributes to ethnic group differences in the experience of pain remains 
unexplored. To address this, the proposed study will characterize the impact of an anti-
catastrophizing cognitive-behavioral intervention on pain-related neural processes and pain 
among NHBs and NHWs with knee OA. NHB and NHW participants with symptomatic knee OA 
will be randomly assigned to a brief pain catastrophizing reduction cognitive-behavioral 
intervention or a control group that will receive pain education. Testing will occur over three days. 
Participants will complete neuroimaging, including assessment of pain-evoked cerebral 
responses and experimental pain testing (i.e., QST) prior to and after the intervention session. 
Standardized quantitative sensory testing approaches will be used to assess experimental pain 
sensitivity, as well as their State Pain Catastrophizing Scale (S-PCS). We hypothesize that 
baseline levels of catastrophizing will be higher among NHB subjects and will predict increased 
pain sensitivity and greater pain-related brain responses among NHB participants.  Moreover, we 
anticipate that the anti-catastrophizing reduction intervention will produce greater reductions in 
reported pain and in pain-related brain activity among NHB versus NHW participants. Findings 
from this proposed study will provide novel information regarding the neural mechanisms whereby 
pain catastrophizing modulates pain and the extent to which these neural processes contribute to 
ethnic group differences in pain responses among NHBs and NHWs with knee OA. This project 
will yield important preliminary data for a future grant application seeking support for a larger scale 
clinical intervention study targeting pain catastrophizing to reduce disparities in pain among older 
adults. 
4. Background: 
 
Clinical osteoarthritis (OA) is the most commonly diagnosed disease with prevalence rates of 
approximately 27 million US adults and rates are projected to increase as the population age [26; 
31], resulting in an annual economic cost of $128 billion [8]. The knee is the most commonly 
affected joint and accounts for the largest proportion of OA burden [54]. Data from a large 

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representative study revealed that non-Hispanic blacks (NHB) have higher odds of being 
diagnosed with radiographic (1.7 times) and clinical (1.5 times) knee OA than non-Hispanic whites 
(NHW) [14]. Furthermore, NHBs with knee OA have higher prevalence rates of radiographic and 
symptomatic knee OA and they experience substantially higher levels of knee OA-related chronic 
pain, functional limitations, and disability compared to their NHW counterparts [2; 22; 52]. In 
addition, NHBs with knee OA show deficits in pain modulation during experimental pain testing, 
such that they evince enhanced pain facilitation and impaired pain inhibition compared to NHWs 
[11]. This quantitative sensory testing profile likely contributes to greater experimental and clinical 
pain sensitivity and may be a phenotype of pain risk in NHBs. Together, these findings suggest 
that ethnic group differences in central pain processing represent a potentially important 
determinant of greater clinical pain among NHBs. While numerous factors likely contribute to 
ethnic differences in OA-related pain and other adverse outcomes [3; 19], interventions targeting 
psychosocial factors have been shown to be a promising avenue to reduce pain and reverse 
aberrant central pain processing in patients with chronic pain [27; 41], but less emphasis has been 
devoted to addressing ethnic differences in knee OA using interventions aimed at addressing 
psychosocial factors [1]. 
A robust psychosocial predictor of enhanced pain and pain-related outcomes is pain 
catastrophizing.  Pain catastrophizing is a tendency to negatively appraise pain-related 
experiences, thereby feeling overwhelmed and having lower perceived ability to cope with and 
control pain, thus, resulting in an amplified pain experience and adverse pain-related outcomes 
(e.g., disability) [30; 43; 44]. Considerable evidence identifies pain catastrophizing as a consistent 
psychosocial variable that predicts poor pain and pain-related outcomes [34; 50] across multiple 
chronic pain conditions [18; 23; 33; 38; 45-47; 51], including in patients with knee OA [6; 28; 29]. 
Numerous studies have documented higher pain catastrophizing in healthy pain-free NHBs 
compared to NHWs during experimental pain tasks [35]. Similarly, investigations of race 
difference in pain catastrophizing in patients with knee OA and other chronic pain conditions, 
suggest NHBs report higher pain catastrophizing during both experimental and clinical pain, 
compared to NHWs [10; 16; 21; 39]. While the importance of intervening on pain catastrophizing 
has been established, research is needed to better understand its neural correlates in order to 
improve treatment efficacy [42]. 
Neuroimaging studies have associated pain catastrophizing with increased cerebral 
responses to pain in several pain-related brain regions (e.g., medial frontal cortex, anterior 
cingulate cortex [ACC], dorsolateral prefrontal cortex [dlPFC], insula, and primary somatosensory 
cortex [SI]) [9; 15; 18; 40], and with increased resting state connectivity between SI and insula 
[27]. A recent systematic review of brain changes associated with pain catastrophizing reveal 
there is some evidence for alterations in gray matter morphology and resting state functional 
connectivity in patients with chronic pain following reduction of pain catastrophizing [32]. Indeed, 
compelling evidence demonstrates that successful reduction of pain catastrophizing following 
cognitive behavioral therapy was significantly correlated with gray matter increase in several pain 
related brain regions (e.g., dlPFC, S1, ACC) [41]. Furthermore, reduction of pain catastrophizing 
with cognitive behavioral therapy resulted in the decoupling of resting state connectivity between 
SI and anterior/medial insula, brain regions not typically connected in a resting state [27]. 
However, Malfliet et al. [32] notes that these studies were observational, which limits conclusions 
about the causal effects of the treatment of pain catastrophizing and its influence on brain 
alterations. Therefore, no neuroimaging study to date has experimentally manipulated pain 
catastrophizing and measured cerebral activity during experimentally-induced pain to determine 
the neural mechanisms whereby catastrophizing impacts pain responses. Moreover, the extent 
to which the influence of pain catastrophizing on these central pathways contributes to ethnic 
group differences in the experience of pain remains unexplored.   
The objective of the proposed research is to experimentally manipulate pain catastrophizing 
in order to investigate the neural mechanisms by which pain catastrophizing influences the 

Protocol #:  201802819 
 
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experience of pain among NHBs and NHWs with chronic pain associated with knee OA. 
Therefore, participants will be randomized to either a 30-minute, single-session catastrophizing 
reduction manipulation or a 30-minute, single-session pain education control group [48; 49].   
 
5. Hypotheses and Specific Aims: 
Specific Aim 1: To characterize the impact of an anti-catastrophizing manipulation on pain-
related neural processes and pain among NHBs and NHWs with knee OA.  
Hypothesis 1a. We hypothesize that the manipulation will produce greater reductions in 
experimental pain and clinical pain among NHBs than NHWs.  
Hypothesis 1b. We hypothesize that the manipulation will produce greater reductions in pain-
related brain responses among NHBs than NHWs. 
 
6. Research Plan: 
The proposed study will enroll 5 NHB and 5 NHW catastrophizing participants with symptomatic 
knee OA. The study will over-enroll 3 additional participants due to attrition over the three-day 
study period. Up to 180 additional participants may undergo screening procedures and will count 
toward screen failures. Potential participants will undergo a standardized telephone or in-person 
screening which will include the pain catastrophizing questionnaire, as well as screening 
questions that inquire about conditions that are listed under our inclusion and exclusion criteria to 
confirm initial eligibility. Participants will be informed that if they do participate in this study, we 
will keep the information the participant provide in addition to information provided to these 
questions as part of this research study. If the participant does not meet inclusion criteria or 
decides not to participate in the study, the participant will be informed that no additional 
information would be collected, but any information up to that point would be maintained. Thirty 
potential participants will be screened to determine initial eligibility. Patients will be excluded if 
they have concurrent medical or arthritic conditions that could confound symptomatic knee OA 
related outcome measures or coexisting disease that could preclude successful completion of the 
protocol including: systemic rheumatic disease/condition, including rheumatoid arthritis, systemic 
lupus erythematosus, gout, and fibromyalgia; a history of clinically significant surgery to the index 
knee (e.g. open reconstruction, knee replacement or major surgery on one or  both knees); 
uncontrolled hypertension (> 150/95); loss of peripheral sensation in areas of the body that will 
be tested with QST; certain neurological diseases that could interfere with protocol completion 
such as s Parkinson’s disease, multiple sclerosis, stroke with loss of sensory or motor function, 
or uncontrolled seizures; cardiovascular or peripheral arterial disease; serious psychiatric 
disorder requiring hospitalization within the past 12 months; diminished cognitive function that 
would interfere with completion of study procedures. Daily opioid use will also be an exclusion, 
as well as a Pain Catastrophizing Score of less than 10. Hospitalization within the preceding year 
for psychiatric illness, serious psychiatric disorder requiring hospitalization within the past 12 
months or characterized by active suicidal ideation or diminished cognitive function that would 
interfere with completion of study procedures. Pregnancy will also be an exclusion. Also, 
contraindications to MRI scanning (e.g. presence of metal implants, claustrophobia) will be 
exclusion criteria. Any criteria for MRI Exclusion, such as the presence of non-removable metallic, 
magnetic material or devices such as pacemakers, aneurism clips, or claustrophobia, which could 
pose a risk for injury in the MRI scanner.  The study will include questionnaires to assess pain, 
clinical symptoms, and pain catastrophizing. All questionnaires provided during this research 
study’s timeline are shown in Table 2. Quantitative Sensory Testing (QST) will be performed at 
the Pain Clinical Research Unit (PainCRU), a fully equipped sensory testing lab within the UF 
Pain Research and Intervention Center of Excellence (PRICE) directed by Dr. Fillingim (mentor). 

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Brain imaging will be performed in the CTSI Human Imaging Core facility, in a 3.0 Tesla whole-
body clinical MRI system (Simens Prisma) and a 32-channel head coil will be used (see study 
Timeline for procedure order). 
The Pain Catastrophizing Scale (PCS) is a reliable and valid (coefficient alpha for total PCS = 
0.87), 13-item scale that assesses catastrophic 
thinking associated with pain [44]. We will 
administer the PCS using traditional instructions 
(a 
measure 
of 
trait 
catastrophizing) 
and 
instructions to assess State Pain Catastrophizing 
Scale 
(S-PCS) 
(“Thinking 
back 
to 
your 
experience during the laboratory pain testing”). 
Clinical Pain. The Western Ontario and 
McMaster Universities Osteoarthritis Index 
(WOMAC) [5] is a reliable (Cronbach’s alpha ≥ 
0.80) and well-validated measure of lower 
extremity pain and function in persons with OA. 
The Graded Chronic Pain Scale (GCPS) evaluates global pain severity and pain-related 
interference over the past 6 months. It yields a “Characteristic Pain Intensity” and an overall 
“Disability” score [53].  The Rapid Estimate of Adult Literacy in Medicine-revised (REALM-R). 
A brief test to measure the participant’s ability to read common medical words, in order to 
determine whether the participant may need assistance with completing questionnaires. 
 
Quantitative Sensory Testing session (QST). Quantitative Sensory Testing Session. Using 
well-established procedures from our laboratory, all participants underwent assessment of 
responses to pressure, and mechanical pain in a laboratory session lasting 30-60 minutes, as 
described previously [16; 50]. Pressure Pain Thresholds (PPT): was assessed at the medial 
and lateral joint lines of the index knee, and at the ipsilateral quadriceps, trapezius muscle and 
lateral epicondyle. Punctate Mechanical Pain: assessed at the patella of the index knee and the 
dorsal aspect of the ipsilateral hand using a nylon monofilament (Touchtest Sensory Evaluator 
6.65) calibrated to bend at 300g of pressure. As in our previous studies [16; 50], participants were 
provide a pain rating following a single contact of the monofilament, after which they provided 
another pain rating following a series of 10 contacts at a rate of one contact per second. The 
difference between pain ratings for the single versus multiple contacts reflects temporal 
summation of mechanical pain.   
Neuroimaging Protocol. A high-resolution, 3D structural scan will be conducted using a T1-
weighted MP-RAGE sequence for use in pre-processing all functional data which will be 
conducted 
between 
stimulus-evoked 
scans 
(Table 1). Two resting state scans will be 
acquired using BOLD-fMRI and pCASL in order 
to examine functional connectivity. Participants 
will be asked to close their eyes during resting 
state scans, but to maintain alertness during the 
scans. 
Any 
difficulty 
staying 
awake 
was 
assessed immediately following the resting-state 
scan. Stimulus-Evoked fMRI and pCASL: 
These procedure will be conducted to assess changes in regional brain activity to painful 
mechanical stimuli applied to the most painful knee of OA patients. Specifically, a monofilament 
that was individually calibrated to produce a moderate pain intensity rating of ≤ 50 out of 100 will 
be applied once per second for a total of five twenty-four second blocks to the index knee, followed 
by an equivalent time period of blunt stimulation (randomized order) with thirty-six second blocks 

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of rest between each mechanical stimuli. One overall verbal pain rating (on the 0-100 scale) will 
be obtained following all stimuli. Data acquisition of all scans will occur in two 50.5-minutes 
imaging session, with 9.5 minutes for set up, resulting in a total 60-minute session.  
Randomization and General Procedures. Individuals will be randomized to one of two groups 
(stratified by sex): 1) a 30-minute, single-session cognitive-behavioral intervention designed to 
reduce pain catastrophizing or 2) a control condition that receives pain education. Testing will 
occur on two days (Figure 1). On Day 1, participants will attend a laboratory session whereby 
informed consent will be reviewed; health, pain, and demographic history will be obtained and 
physical examination will be performed to identify the most symptomatic knee. Female 
participants of childbearing potential will complete a one-time pregnancy test at the beginning of 
the session on day one.  Trait pain catastrophizing will be assessed prior to 
pain testing. Day 1 session is expected to last up to 1.5 hours. On Day 2, 
participants will undergo neuroimaging acquisition followed by assessment 
of State Pain Catastrophizing Scale (S-PCS) in response to the pain-
evoked cerebral responses (see neuroimaging protocol above). Then, 
participants will complete QST assessment of responses to pressure (i.e., 
pressure pain threshold), and punctate mechanical stimuli (i.e., temporal 
summation of mechanical pain) in a laboratory session lasting 30-60 
minutes. State Pain Catastrophizing Scale (S-PCS) will be assessed 
immediately after each pain induction procedure. There will be a 30-minute 
rest period between the neuroimaging and QST session. Day 2 session is 
expected to last 2.5 to 3 hours. On Day 3, each participant will receive either 
the cognitive-behavioral intervention or the pain education (control 
condition), followed by post-tests that will be identical to the pre-tests given 
on Day 2, except that participants in the pain catastrophizing reduction 
group will be told to use the coping strategies they learned. Once all testing 
is over, participants will be debriefed and provided with an honorarium. Day 
3 testing session is expected to last 3 to 3.5 hours. Audio recording will be 
conducted at the end of the study in order to obtain feedback on what 
intervention techniques participants used and whether they noticed any 
difference during Day 3 testing. We will audio record responses to the following questions: 1) 
during this last testing, please tell us what you were able to do; 2) describe how you applied your 
techniques; 3) did you notice any difference in your reactions to the stimulations; and 4) what did 
you notice? Further, participants will be asked to rate on a scale from 0-10 how well they were 
able to use the strategies and how effective they felt the strategies were. These recording will be 
reviewed by the study team to assess the quality of our treatment visits. These recording will not 
be released and will only be accessible by study investigators. At the end of the study, the 
recordings will be transcribed and the audio recordings will be destroyed. State Pain 
Catastrophizing Scale (S-PCS) will be used as a manipulation check to verify that catastrophizing 
was effectively. Pain Catastrophizing Reduction Group: The cognitive-behavioral intervention 
will comprise three components: 1) general education about pain (e.g., pain pathways) and a 
rationale for the intervention (e.g., gate control theory); 2) impact of positive and negative pain-
related thoughts on neural process of pain; and 3) a guided imaginal pain exposure exercise. We 
and others have successfully applied these and similar approaches to reducing pain 
catastrophizing [12; 13; 48; 49] (see manual for details). Pain Education Group: This group will 
receive general information about the neurobiology of pain and knee OA. At no time will they be 
taught about pain modulation or the interface of thoughts, feelings, and pain [48; 49]. 
FMRI Analyses. Resting State BOLD: We will perform functional connectivity analysis. Briefly, 
the BOLD images will be pre-processed using MATLAB Statistical Parametric Mapping software 
(SPM12) scripts [17]. The images will be slice time corrected, realigned, and resliced into 2mm x 
2mm x 2mm voxel sized images and spatially normalized to an EPI template. Movement artifacts 

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are processed using the paradigm set forth in [7; 37]. Movement effects are first regressed from 
the BOLD signal. If movement is greater than 0.5mm, bad volumes will be identified and replaced 
with interpolated values (using nearest neighbor interpolation). Effects attributed to cerebrospinal 
fluid and white matter will then be regressed out from the BOLD signal. The whole data set is 
temporally smoothed using a band-pass butterworth filter (freq=[0.01 0.08]) and spatially 
smoothed using a Gaussian model (6 mm kernel), and interpolated volumes removed. Functional 
connectivity (r to z transformed correlations coefficients) between regions of interest (ROIs) 
associated with pain catastrophizing [27] (dorsolateral prefrontal cortex and anterior cingulate 
cortex, and insula and SI) will be assessed using the CONN Toolbox [55]. Evoked-Pain Scans: 
mechanical stimuli will be applied once per second for 10 twenty-four second periods with 36 
seconds of rest periods following each stimulus series for the scan duration (as in [20]). 
Preprocessing steps will include: motion correction, residual motion effect removal, denoising, co-
registration, spatial smoothing, and normalization. Based on the existing literature on pain-evoked 
stimuli, we will examine the following ROIs [4; 36]: anterior cingulate cortex, dorsolateral prefrontal 
cortex, and the periaqueductal gray [PAG]. These ROIs will be selected with the Wake Forest 
University pick atlas, which uses the Talairach Daemon database [25]. 
Data Analysis. Procedures will be put in place to ensure data integrity and the protection of 
subject identification. Data will be inspected for distributional form, missing values, and 
implausible values. We will compare data on study completers and those lost to follow-up to 
investigate potential biases. The assumption of normality will be checked using histograms and 
normal probability plots. The assumptions of regression and mediation models will be checked 
using residual plots and plots of influence statistics. All statistical analyses will be conducted with 
statistical software SAS version 9.4 (Cary, N.C.) and R version 3.2.2 (The R Foundation for 
Statistical Computing). All hypothesis testing conducted to address the primary aim (comparing 
ethnic groups on pain-related brain function, clinical pain, and pain sensitivity measures) will be 
two-sided with a Bonferroni corrected level of significance of .004 (.05 divided by 12 tests). 
Hypothesis testing using ANCOVA models will also be two-sided with a Bonferroni corrected level 
of significance of .004. We will control for SES and discrimination in all analyses. 
 
We will use separate ANCOVA models to investigate the effect of the manipulation (the 
independent variable) on pain-related neural processes and pain measures. The measures at 
baseline are the covariates while the measures post-manipulation are the dependent variables. 
We will again use separate ANCOVA models which will include an ethnic group variable and an 
manipulation-ethnic group interaction term to test the hypothesis that the manipulation will 
produce differentiated pain-related brain responses due to ethnicity. 
 
7. Possible Discomforts and Risks: 
 
Potential Risks: 
 
While generally safe, the experimental pain procedures confer some limited risks. 
One risk common to all procedures is that the participant will experience pain or discomfort. 
Specific risks of each procedure are discussed below. 
 
 
Pressure Pain Procedure: There is a slight chance that a bruise may form as a result of 
the pressure pain procedure. Also, some patients may experience after-sensations after 
application of pressure stimuli to their symptomatic knee, though this is expected to be brief in 
duration. Also, this risk is diminished by applying brief stimuli well below the participant’s tolerance 
level. 
Magnetic Resonance Imaging (MRI): MRI scanning does not expose subjects to any 
physical risks by itself. All subjects will be carefully screened for the presence of magnetic material 
or devices, like pacemakers, etc. that could pose a risk for injury in the MRI scanner. They will 

Pr ot o c ol # :  2 0 1 8 0 2 8 1 9  
 
P a g e 8 of 1 2  
I R B v er si o n:  3/ 9/ 2 0 0 4  
PI v er si o n:  3/ 3 0/ 2 0 2 2  
o nl y b e all o w e d i nt o t h e m a g n et if m a g n eti c or el e ctr o ni c it e m s c a n b e r e m o v e d pri or t o s c a n ni n g. 
S o m e s u bj e ct s w h o e x p eri e n c e f e ar of e n cl o s e d s p a c e s  (i. e. cl a u str o p h o bi a) m a y n ot b e a bl e t o 
u n d er g o br ai n M RI s c a n ni n g. P arti ci p a nt s will al s o b e c ar ef ull y s cr e e n e d f or cl a u str o p h o bi a b ef or e 
c o n d u cti n g f M RI s c a n n i n g. 
 
Pr ot e cti o n s A g ai n st Ri s k : 
 
T h e e x p eri m e nt al p ai n pr o c e d ur e s d e s cri b e d i n t hi s a p pli c ati o n ar e wi d el y u s e d a n d s af e 
pr o c e d ur e s.  W hil e  t h e y pr o d u c e  p ai n,  ri s k  t o t h e  s u bj e ct  i s mi ni m al,  b e c a u s e:  1)  t h e p ai n i s 
tr a n si e nt  i n  n at ur e,  a n d  g e n er all y  s u b si d e s  i m m e di at el y  aft er  t h e  pr o c e d ur e;  2)  s u bj e ct s  ar e  
i n str u ct e d t h at t h e y m a y st o p a n y pr o c e d ur e at a n y ti m e wit h n o a d v er s e c o n s e q u e n c e s; a n d 3) 
t h e  l e v el  of  p ai n  e x p eri e n c e d  b y  s u bj e ct s  i s  b el o w  t h eir  t ol er a n c e  l e v el.  Al s o,  ri s k s  will  b e  
mi ni mi z e d b y a d h eri n g t o o ur e x cl u si o n crit eri a. S p e cifi c pr ot e cti o n s i n cl u d e d i n e a c h pr o c e d ur e 
ar e di s c u s s e d b el o w.  
 
Pr e s s ur e P ai n Pr o c e d ur e : T h e ri s k s of br ui si n g a n d li n g eri n g p ai n will b e di mi ni s h e d b y 
a p pl yi n g bri ef sti m uli w ell b el o w t h e p arti ci p a nt’ s t ol er a n c e l e v el.  
M RI Pr o c e d ur e s : T h e pri m ar y ri s k of M RI i n v ol v e s s c a n ni n g i n t h e pr e s e n c e of m a g n eti c 
i m pl a nt s or m at eri al att a c h e d t o t h e p arti ci p a nt. Al s o, cl a u str o p h o bi c r e s p o n s e s c a n b e a n ot h er 
ri s k. T h e s e ri s k s will b e mi ni mi z e d t hr o u g h c ar ef ul s cr e e ni n g of p arti ci p a nt s, b ot h o v er t h e p h o n e 
a n d a g ai n i n -p er s o n pri or t o t h e i m a gi n g pr o c e d ur e. Al s o, p arti ci p a nt s will b e i nf or m e d t h at t h e y 
c a n di s c o nti n u e t h e pr o c e d ur e at a n y ti m e s h o ul d t h e y b e c o m e u n c o mf ort a bl e. O ur t e a m will 
o b s er v e t h e f oll o wi n g pr o c e d ur e s t o r e d u c e ri s k s a s s o ci at e d wit h t h e M RI pr ot o c ol.  
 
M RI Pr e -S c a n Pr o c e d ur e s  
 
All s u bj e ct s i n o ur st u d y will b e s cr e e n e d f or st a n d ar d M RI c o ntr ai n di c ati o n s, i n cl u di n g b ut 
n ot li mit e d t o:  
 T h e pr e s e n c e n o n -r e m o v a bl e f err o u s m et al o bj e ct s 
 A n e ur y s m cli p s  
 Pa c e m a k er s  
 Ot h er c o ntr ai n di c ati o n s s u c h a s d efi brill at or s, et c.  
 Cl a u str o p h o bi a or ot h er s u bj e cti v e di s c o mf ort i n t h e s c a n ni n g e n vir o n m e nt  
 
S u bj e ct P o siti o ni n g:  
 
Pr o p er p ati e nt p o siti o ni n g i s a k e y a s p e ct f or a s u c c e s sf ul a n d c o mf ort a bl e M RI e x a m. All s u bj e ct s 
will b e p o siti o n e d i n t h e s a m e m a n n er f or M RI s c a n ni n g. A s a k e y c o m p o n e nt of o ur M RI s c a n ni n g 
q u alit y c o ntr ol t o i n s ur e c o n si st e nt a n d s af e i m a gi n g of t h e br ai n, t h e f oll o wi n g p ati e nt p o siti o ni n g 
pr o c e d ur e h a s b e e n e st a bli s h e d:  
1. Pl a c e cl e a n s h e et o n s c a n n er t a bl e a n d c oil cr a dl e.  
2. R e m o v e all u p p er b o d y cl ot hi n g wit h m et alli c tri m, s u c h a s zi p p er s, b utt o n s or e m br oi d eri e s 
t h at m a y c a u s e artif a ct s i n t h e M RI i m a g e s. 
3. Pr o vi d e e a c h p ati e nt wit h e ar pr ot e cti o n ( e ar pl u g s a n d a h e a d s et).  
4. P o siti o n t h e p ati e nt s o t h e h e a d a n d n e c k ar e r el a x e d, b ut wit h o ut r ot ati o n i n eit h er pl a n e. T h e 
p ati e nt  s h o ul d  al s o  b e  w ell  s u p p ort e d  i n  t h e  h e a d  c oil  t o  m a xi mi z e  c o mf ort  a n d  mi ni mi z e  
m o v e m e nt.  
5. Pill o w s ar e pl a c e d u n d er t h e l e g s t o h el p t o d e cr e a s e str ai n o n t h e k n e e s a s w ell a s a s si sti n g 
i n t h e st a bili z ati o n of m oti o n i n t h e l o w er b o d y. 
6. O n c e t h e p ati e nt h a s b e e n p o siti o n e d, pl a c e s p o n g e s al o n g t h e si d e s of h e a d f or st a bili zi n g 
s u p p ort a n d r e d u cti o n of m oti o n.  

Protocol #:  201802819 
 
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7. Align the centering crosshairs on the patient’s nasion (directly between the eyebrows) at every 
scanning session. 
8. Center the head coil over the patients’ head, making sure that the patient is high enough in the 
coil to ensure there is no drop off at the inferior aspect of the brain. 
9. The subject is given an alarm ball, and instructed to squeeze the alarm ball in case he/she 
wants to have the scanning discontinued or needs to initiate communication with the operator of 
the scanner. 
10. The subject is reminded to hold as still as possible and is then advanced to the iso-center of 
the scanning bore. 
 
These procedures ensure maximum patient safety and comfort while allowing successful and 
reliable imaging of the brain. 
 
8. Possible Benefits: 
 
These risks are small relative to the potential benefits to be realized from conducting this research. 
While participants will not directly benefit from this research, it is hoped that the information to be 
gained will benefit society by providing new information regarding the neural factors by which pain 
catastrophizing influence pain and the underlying ethnic group differences in pain and disability. 
 
9. DSMP (Data and Safety Monitoring Plan): 
The current study is not a Phase III clinical trial nor does not involve multiple field sites. However, 
the current study involves greater than minimal risk, therefore, a formal data safety and monitoring 
board will not be required.  In order to ensure data integrity and safety of human subjects, all 
adverse events will be reported to both the IRBs and the General Clinical Research Center for their 
external review.  Any subsequent recommendations regarding protocol changes will be 
implemented.  In addition, the PI (Ellen L. Terry) will review the reported adverse events every 
three months and will conduct interim data analyses to minimize the risk to the study subjects. 
10. Conflict of Interest: 
 
The PI (Ellen L. Terry) has no conflict of interest to disclose. 
 
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