Retuning the Nervous System in Youth With Chronic Pain
Phase: EARLY_PHASE1
Conditions: Ehlers-Danlos Syndrome (EDS), Complex Regional Pain Syndrome (CRPS), Amplified Musculoskeletal Pain Syndrome (AMPS), Low Back Pain, Fibromyalgia, Chronic Widespread Pain
Sponsor: Children's Hospital Medical Center, Cincinnati

                                                              Retuning the Nervous System in Youth with Chronic Pain 
 
NCT03686748                                                                                                                                  August 16, 2019 
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Study Title: 
Retuning the Nervous System in Youth with Chronic Pain 
Investigators: 
Robert C. Coghill, Ph.D. 
Flavia Di Pietro, PT, Ph.D. 
Kenneth R. Goldschneider, M.D. 
Sara E. Williams, Ph.D. 
 
 

                                                              Retuning the Nervous System in Youth with Chronic Pain 
 
NCT03686748                                                                                                                                  August 16, 2019 
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Protocol Version:  
4.0 
 
1 
SPECIFIC AIMS 
Pain in both youth and adults is a complex, subjective and personal experience, and 
remains poorly understood.  One particularly perplexing dimension of some forms of 
pain is the tendency of pain to spread outside of an affected body site to adjacent 
location, and then to unaffected body sites.  Such widespread pain may reflect an 
altered spatial tuning of somatosensory processing, such that lateral inhibition is 
diminished, thereby allowing pain to spread.  To date, no therapies exist which are 
designed specifically to diminish or even reverse the spatial spread of pain.  However, 
training in two-point discrimination holds the potential to retune spatial aspects of 
somatosensory processing and may represent a novel therapy for widespread pain.  
Thus, the present investigation will test the following aims: 
Aim 1. Do youth with chronic pain have disrupted spatial tuning of somatosensory 
processing? Deficits in two point tactile discrimination have long been noted in adults 
with chronic pain, but such deficits remain poorly documented in pediatric chronic pain 
patients.  In order to determine if such deficits exist, youth with both chronic pain and 
healthy youth will undergo assessment of two point discrimination thresholds.    
Aim 2.  Does two-point discrimination training result in diminished pain and disability 
in youth with somatic pain?  After initial characterization of tactile discrimination 
thresholds, youth with chronic pain will participate in multiple sessions of either two-point 
discrimination training or a single-point spatially-directed attentional control condition.  
Training will involve up to 9 additional sessions.  Efficacy of training will be assessed by  
1) reductions in the spatial extent of pain, 2) reductions in pain intensity and 
unpleasantness, and 3) reductions in pain-related disability.   
 
2 
SIGNIFICANCE AND INNOVATION 
2.1 Scientific Premise 
Highly disabling persistent pain is a frequent complaint in children, with prevalence 
estimated at approximately five percent in Western societies (Huguet and Miro, 
2008; Hechler et al., 2014). Pain prevalence rates increase with age (King et al., 
2011) and as such, chronic pain in adolescence represents a significant economic 
problem in the USA (Groenewald et al., 2014). Adolescence is a critical period for 
development physically, psychologically and socially, and pain severely interferes 
with such an important phase of life (O'Sullivan et al., 2012). Adequate management 
of pain in adolescents should clearly be a goal in itself, but the evidence suggests 
that management of pain in young people may also help prevent pain in adults 
(Hestbaek et al., 2006). 
From a mechanistic standpoint, fundamental questions about pain remain 
unanswered, and this has meant the treatment needs of pain sufferers have largely 
been unmet. To date the intensity of pain has been a focus of investigation and 

                                                              Retuning the Nervous System in Youth with Chronic Pain 
 
NCT03686748                                                                                                                                  August 16, 2019 
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treatment, but pain intensity is only one dimension of the pain experience. Research 
into the spatial dimension of pain has been grossly neglected in comparison; we still 
do not fully understand how the nervous system processes and spatially tunes 
incoming sensory information from the body. This avenue of inquiry is critical, given 
that one of the most common and intriguing symptoms of chronic pain is the spread 
of pain well beyond the site of the original injury. Our knowledge of sensory function 
in adolescents is particularly lacking. 
Several lines of evidence point towards abnormal processing of sensory information 
in adult patients with chronic pain disorders. For example, when it comes to a painful 
body part, sufferers are typically unable to perceive the sensation of two individual 
stimuli on the skin when those two points are located close together in space (termed 
two-point discrimination) (Flor et al., 2001; Lotze and Moseley, 2007; Wand et al., 
2010). This poor tactile acuity indicates abnormality in the nervous system’s normal 
spatial tuning, or surround inhibition, of sensory information; in patients it appears 
that each sensory stimulus is not activating a distinct population of neurons as it 
would in a healthy pain-free person (Defrin et al., 2008),(Gardner et al., 2000). Poor 
tactile acuity has been correlated with pain intensity (Flor et al., 2006; Lotze and 
Moseley, 2007) and with the spread of pain (Maihofner et al., 2003, 2004). Not only 
do patients with CRPS have impaired 2-point discrimination in their affected 
extremities compared with their unaffected extremities, but they also have diminished 
ability to learn 2-point discrimination in comparison with control subjects (Maihofner 
et al, 2007). All this suggests a global impairment in spatial tuning within and in 
comparison to external controls. 
An important randomized trial in adults with phantom limb pain trained patients’ 
tactile acuity with repeated stimulation over the stump. The training led to improved 
pain levels, together with increased tactile acuity and reversal of the associated 
abnormal brain activation patterns (Flor et al., 2001). Regarding chronic limb pain, 
Moseley and colleagues found that repetitive stimulation of the skin improved pain 
levels and patients’ tactile acuity in the affected area (Moseley et al., 2008). 
Importantly, the stimulation program involved instructions on attending to and 
evaluating the nature of the stimulation – that is, a discrimination task. Tactile 
stimulation alone did not have the same effects.  
Our translational work with spatial aspects of pain provides a mechanistic rationale 
for extending and refining the work of Moseley.  First, using lasers to deliver noxious 
heat in two different patterns - two simultaneous points (4-8 cm separation distance, 
5 mm diameter) or a contiguous line (4-8 cm long, 5 mm width), we sought to identify 
a psychophysical correlate of lateral inhibition (Quevedo et al., 2017).  Despite the 
considerably larger surface area being stimulated with the line, participants 
perceived the two point stimuli as more intense.  This suggests that, in healthy 
individuals, there is a lateral inhibition that was recruited by the line stimuli, but not by 
the two point stimuli (Quevedo et al., 2017).   
This lateral inhibition may be modified by attention.  Using contact heat stimuli, we 
routinely demonstrate spatial summation of pain (i.e., enhanced pain response) 
when two stimuli are delivered at 10 cm separation distances.  This occurs when 

                                                              Retuning the Nervous System in Youth with Chronic Pain 
 
NCT03686748                                                                                                                                  August 16, 2019 
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participants are instructed to make one overall rating of pain.  However, when 
subjects are given a different attentional directive - i.e. to rate pain from each probe 
separately - spatial summation of pain is abolished and some inhibition is generated 
(Quevedo and Coghill, 2007).  We have hypothesized that to accomplish this task, 
lateral inhibition at some level of the neuraxis is increased by the attentional 
directive.  This, in turn, minimizes spatial interactions among populations of neurons 
responding to each stimulus, and abolishes spatial summation.  Moreover, this 
increased lateral inhibition may sufficiently reduce the total population response to 
account for inhibition unmasked at distal stimulation sites (Quevedo and Coghill, 
2007). 
Despite this growing body of research in adults, demonstration of these processes in 
children and adolescents is lagging behind. What if we were able to demonstrate 
deficits in and restore spatial tuning of the sensory nervous system in adolescents 
with widespread pain? This project aims to meet this objective, using a targeted and 
innovative treatment paradigm. 
2.2 Innovation and Importance of this Study 
To date, there are no therapies targeted specifically at minimizing and reducing the 
spatial spread of pain.  As such, if this study is successful, an important new therapy 
for pain may emerge. 
2.3 Supporting Data-Previous Evidence  
The proposed investigation is highly novel and builds on our prior spatial studies 
described above.  To date, no investigations have used two point discrimination 
training to demonstrate deficits in children and adolescents with chronic pain as have 
been found in adults or as a potential treatment for widespread pain. 
 
3 
STUDY DESIGN 
Prior to commencing this investigation we will optimize the tactile discrimination 
threshold testing (i.e. as per baseline visit, below), and the training conditions, in up to 
ten participants (patients and/or healthy controls). This will serve as a pilot to refine 
operational aspects of study procedures before we commence the main investigation 
proposed herein. Following this, youth with either chronic pain (ages 10-17, n=40) or 
healthy youth (ages 10-17, n=20) will undergo assessments of two-point and single-point 
discrimination thresholds in an initial session (Aim 1).  After this initial session, youth 
with chronic pain will participate in up to 9 additional sessions of attentional training (Aim 
2).  These chronic pain patients will be randomized to either two-point discrimination 
training (n=20) or a single-point spatially-directed attentional control condition (n=20).  
Participants will not be informed of which intervention they will receive (single-blind 
study).  Psychological questionnaires will be completed in the first and last sessions in 
order to determine how these variables relate to tactile discrimination and response to 
training. 
  

                                                              Retuning the Nervous System in Youth with Chronic Pain 
 
NCT03686748                                                                                                                                  August 16, 2019 
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4 
SELECTION AND ENROLLMENT OF PARTICIPANTS 
4.1 Inclusion Criteria 
Chronic Pain Patients:  
Somatically located chronic pain including amplified musculoskeletal pain syndrome, 
complex regional pain syndrome, low back pain, fibromyalgia, other forms of chronic, 
widespread pain.  
Male or female, 10-17 years (inclusive) 
High fluency in written and oral English language 
Control Participants:  
Youth in good general health  
Male or female, 10-17 years (inclusive) 
High fluency in written and oral English language 
4.2 Exclusion Criteria 
Present significant mental health disorder as defined by DSM V (e.g. psychosis, 
bipolar disorder, major depression), alcohol or drug dependence, or documented 
developmental delays or impairments (e.g., autism, cerebral palsy, or mental 
retardation) of a magnitude that would interfere with adherence to study 
requirements or safe participation in the study 
Primary complaint of migraine or visceral (abdominal) pain, with minimal somatic 
pain. 
4.3 Participant Withdrawal Criteria  
Participant (or legal guardian) declines further study participation. 
Participant fails to comply with experimental protocol or instructions of study staff. 
Identification of brain, neurologic, or severe psychiatric abnormalities that may 
confound procedures. 
In the investigator’s judgment, it is in the participant’s best interest. 
 
5 
STUDY INTERVENTIONS 
5.1 Two Point Discrimination Training: Two-point discrimination threshold (TPD) 
training may be performed 1) at spatial locations remote from pain, 2) at spatial 
locations adjacent to the region of pain, and/or 3) at spatial locations in the site of 
pain, if the participant will tolerate it. TPD is defined as the smallest distance 
between two points at which someone can recognize two points, and not one, 
touching their skin. As such this is a test of one’s ability to identify separate 
stimulation of two discrete areas, and relies heavily on lateral inhibition. Highly 

                                                              Retuning the Nervous System in Youth with Chronic Pain 
 
NCT03686748                                                                                                                                  August 16, 2019 
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precise mechanical calipers will be gently placed onto the skin and the distance 
between the prongs will be increased/decreased. After repeated decreases and 
increases in the distance between the prongs, the TPD will be deemed as the 
distance at which participants consistently report two points instead of one (Moseley 
et al., 2008,)(Wand et al., 2010). One-point stimuli will be interleaved to serve as a 
control condition. Participants will be informed immediately of correct and incorrect 
responses as part of the discrimination training. 
5.2 Control Stimulation: Participants will undergo a single-point discrimination training 
at the same sites as described above.  We will employ a discrimination paradigm 
similar to that described by Moseley et al. (2008).  Probes of different sizes will be 
used for this portion - a small diameter probe (~1-5 mm) and a large diameter probe 
(~6-50mm). The probes will be gently placed in contact with the participants' skin, 
and the participant will be instructed to respond if they were contacted with the small 
or large probe. Participants will be informed immediately of correct and incorrect 
responses as part of the discrimination training.   
 
6 
STUDY PROCEDURES AND MEASURES 
6.1 Study Recruitment/Enrollment Procedures  
The primary methodology for identifying and recruiting chronic pain patients for this 
study will be through identification of potential participants from the inpatient and 
outpatient chronic pain clinics at Cincinnati Children’s Hospital Medical Center, as 
well as community advertisements.  Over the course of this project, we will enroll up 
to 50 patients. 
Healthy control participants will be identified via word-of-mouth recruitment as well as 
advertisements throughout the community.  We will enroll up to 30 healthy control 
participants.   
Methods and processes for identifying patients will be conducted in accordance with 
the Declaration of Helsinki and Good Clinical Practice Guidelines. 
To support our recruitment and retention, progress will be evaluated weekly and 
existing challenges and potential solutions will be discussed with the study team to 
ensure we meet our projected timeline. 
6.2 Consent/Assent Procedure 
Participants and parents/guardians will be given ample time to read the consent 
document.  To ensure comprehension, the experimenter will ask a brief series of 
questions to ensure that both participants and/or parents/guardians understand key 
aspects of the study.  Once comprehension has been demonstrated the participant 
and parents/guardian will sign the consent form.  The experimenter will then sign the 
consent form. A copy of the signed consent form will be provided to participants.  
This procedure will be documented on a form which will be placed in the participants' 
folder. 

                                                              Retuning the Nervous System in Youth with Chronic Pain 
 
NCT03686748                                                                                                                                  August 16, 2019 
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6.3 Participant Characterization 
Medical History: A medical history will be completed to capture pain diagnosis, 
medication usage, and concurrent conditions. This will be augmented and 
crossreferenced with information from the participant's medical record. 
Body Morphometry: Height, weight, and hip and waist circumference will be obtained. 
Menstrual Cycle: Position in the menstrual cycle will be noted by onset of last 
menstrual period in women who are not on oral contraceptives.  For women on oral 
contraceptives, the phase of the cycle will be determined by the contraceptive pill 
packet.  
6.4 Pain Assessment 
Psychophysical Assessment of Pain Magnitude:  Pain intensity and pain 
unpleasantness will be assessed by mechanical and computerized visual analogue 
scales (VAS) (Price et al., 1994).  These scales have been repeatedly demonstrated 
to 1) provide reliably separate assessment of intensity and unpleasantness, 2) to be 
internally consistent, and 3) to approximate ratio scale measurement accuracy 
(Price, 1999).  Participants will be instructed in their use via a radio analogy (Price et 
al., 1989). These scales have been used extensively by the PI in ongoing studies in 
youth.  We may also provide auditory stimuli via calibrated headphones (up to 95 dB 
for 10s) to provide a cross-modality training procedure to reinforce the concepts of 
intensity and unpleasantness. 
Pain and Symptom Assessment Questionnaire: This questionnaire documents pain 
location and additional pain related symptoms. 
Assessment of Pain Location:  Pain location will be characterized by having the 
participant draw regions of pain on a paper or electronic body map or photo of 
themselves.   
6.5 Psychological Assessment/Questionnaires 
Variation in psychological states can contribute substantially to the construction of 
the experience of pain, and may importantly influence attentional processes related 
to pain. Thus, participants will undergo extensive psychological characterization with 
a particular focus on variables known to influence pain.  Many scales will be useful 
for enabling comparisons of these patients with chronic pain patients in other studies, 
and are part of our standard testing battery.  
Anxiety: The PROMIS Anxiety pediatric scales will be used to assess anxiety. The 
SCARED anxiety scale will be used to further characterize anxiety. 
Mood and Affect:  The PROMIS Depression pediatric scales will be used to assess 
depression. The Positive and Negative Affect Schedule - Expanded will be used to 
characterize mood and affect.  
Mindfulness: The Freiburg Mindfulness Inventory will be used to assess mindfulness. 
Impulsivity: The Barratt Impulsiveness Scale will be used to assess impulsivity.  

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Handedness:  The Edinburgh Handedness Inventory will be used to assess the 
degree of handedness and will be critical in the interpretation of differences in the 
lateralization of nociceptive processing.  
Sleep: Sleep deprivation may substantially alter pain sensitivity.  The Epworth 
Sleepiness Scale will be used to quantify the level of daytime sleepiness, while the 
Pittsburgh Sleep Quality Index will be used to assess sleep quality. 
Pain Interference, Disability, and Catastrophizing: The PROMIS Pain Interference 
Scale (pediatric version) will be used to assess how much pain interferes with daily 
living. Pediatric versions of the pain catastrophizing scale will be used to assess 
pain-related catastrophizing, while the Functional Disability Index will be used to 
characterize disability.     
Social Status and Discrimination:  Insurance, income, education level, and 
experience of discrimination will be used to quantify socio-economic variables. 
7 Study Visits  
The duration of two-point discrimination needed to improve pain remains completely 
unknown.  To optimize retention, we may truncate the number of visits, depending on 
subject availability, with procedures in Visit 10 being performed at the final visit.  Healthy 
control participants will only participate in the baseline visit. 
7.1 Baseline + Intervention - Visit 1 (up to 3 hours) 
Completion of informed consent/assent prior to initiation of study procedures 
Obtain information for payment, provide ClinCard 
Randomize to intervention 
Review medical history 
Document all concomitant medications including prescribed, over the counter, and 
nutraceutical supplements 
Administer questionnaires  
Assess pain intensity, unpleasantness, qualitative aspects of pain 
Assess spatial extent of pain (body map or patient’s own photo) 
Demonstration of two-point/single-point discrimination procedure 
Assess two-point/single-point discrimination 
Initiate intervention (TPD training or Control) 
Assess pain intensity, unpleasantness 
Assess spatial extent of pain 
7.2 Intervention - Visits 2-9 (1 hour) 
Determine any changes in medications or concurrent conditions 
Assess pain intensity, unpleasantness, qualitative aspects of pain 

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Assess spatial extent of pain 
Continue intervention (TPD training or Control) 
Assess pain intensity, unpleasantness, qualitative aspects of pain 
Assess spatial extent of pain 
7.3. Intervention+Completion - Visit 10 (up to 3 hours) 
Assess pain intensity, unpleasantness, qualitative aspects of pain 
Assess spatial extent of pain 
Final intervention (TPD training or Control) 
Assess two-point/single-point discrimination 
Assess pain intensity, unpleasantness, qualitative aspects of pain 
Assess spatial extent of pain  
Administer psychological questionnaires 
Note that some of the procedures above may be omitted for the purpose of 
streamlining the study visits, or if procedures are deemed to be incongruent with the 
participants’ ongoing clinical treatments. Omitting these procedures would reduce 
participant burden and would have no impact on safety. 
  
8. SAFETY ASSESSMENTS AND MONITORING 
This study involves no increase over minimal risk, so a Data Safety Monitoring Board will not 
be created for this study.  Any adverse events related to the study procedures will be 
reported to Cincinnati Children’s Hospital Medical Center’s Institutional Review Board.   
9. STATISTICS 
9.1 Statistical Analysis Plan 
Aim 1: 
A mixed model analysis of variance will be utilized to determine differences between 
groups (chronic pain patients vs. healthy controls - between factor) and body site (within 
factor), and group X body site interactions. 
Aim 2: 
To maximize the utility of data collected, a mixed model analysis of variance will be 
utilized to determine differences between groups (between factor), differences over time 
(within factor), and time X group interactions. 
Outcome variables of interest include 1) reductions in area of pain, 2) reductions in pain 
intensity and unpleasantness, 3) reductions in pain-related disability 

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Control variables include: 1) Improvements in tactile discrimination thresholds, 2) data 
from psychological questionnaires.  These variables may be added as covariates to 
the overall model, or may be used to perform a manipulation check. JMP or R software 
will be used to perform analyses 
9.2 Number of Participants to be Enrolled 
This is the first investigation of an entirely novel question, and will be used to determine 
both effect size and variability.  Thus, we will apply a heuristic approach based on prior 
experience obtained within-subjects variability in pain ratings in studies of spatial 
aspects in acute experimental pain in healthy adults (Quevedo and Coghill, 2007; 
Quevedo et al., 2017). With these studies, we have obtained reproducible results from 
15 subjects in within subjects designs.  Thus, we have selected N=20 per group to 
compensate for the reduced power of the between subjects design.  Up to 10 additional 
participants will serve to optimize operational aspects of study procedures as potential 
pilot subjects. 
9.3 Level of Significance 
Statistical significance will be defined by p<0.05.  
9.4 Participants to be Included in Analyses  
All participants without excessive missing data (i.e. completion of <5 sessions) will be 
included in analyses.  
10. DATA MANAGEMENT   
An Electronic Data Capture (EDC) system that is designed to support reliable and 
secure entry of non-imaging data will be used for the study. Paper forms will be used for 
sensory testing data and may be used as backups for questionnaires in the event of 
computer malfunction during data acquisition.  
10.1 Data Entry 
Data can be entered directly via a fully validated and 21 CFR Part 11 compliant, secure 
application and stored centrally. Data will be entered by subject study identification 
number; names will not be linked with participant data in the database.  
10.2 Data Validation and Monitoring 
Real time validations can be integrated into the data entry system.  Inconsistent or 
questionable values can be flagged during entry, and reports can be automatically 
generated to the data entry client.  These reports provide the information necessary to 
investigate any data entry errors or resolved questions regarding out-of-range or 
questionable values.  
10.3 Data Security and Integrity 
All data changes are written to an audit trail. The audit trail identifies the data item by 
table, column and key field. The entry includes the user, date and time, as well as the 

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old value and new value. Data are saved at regular intervals during data entry to prevent 
loss of information in the event of a disruption of the Internet connection.  
Several levels of security are employed to ensure privacy and integrity of the study data, 
including the following: Study access requires use of assigned user names and 
passwords. Individual roles and access levels are assigned by the study data manager. 
Passwords are changed regularly. Web-based entry uses secure socket layer data 
encryption.  Data with identifiers will not be stored on laptop computers. 
11. ETHICS AND HUMAN PARTICIPANTS CONSIDERATIONS 
11.1 Potential Risks and Minimization of Risk 
Psychological Distress. There is a chance that participation in this study could cause 
psychological distress. The psychological questionnaires could make some participants 
uncomfortable.  
Sensory Testing. The sensory stimuli will consist of innocuous tactile stimuli delivered for 
the two-point discrimination as well as the one point attentional control conditions.  
These stimuli are similar to those utilised during clinical practice and encountered during 
daily life, and pose minimal risk. Specifically, application of these stimuli to pain-free 
areas would never be expected to generate pain or cause tissue damage. In patients, 
testing in zones of chronic pain could possibly increase ongoing pain or could produce 
prolonged aftersensations. Testing in these zones is fully optional; if testing exacerbates 
pain, the participant can choose for the testing to be undertaken in a pain-free area, or 
testing can be immediately terminated if requested. 
11.2 Reporting of Incidental Findings 
We will collect contact information for the pain physician of each participant on the first 
visit.  In the case that abnormal findings are identified, the participant’s physician will be 
contacted by the PI, or a designee of the PI and the findings reported. 
There is a small chance that psychological assessments and other procedures may 
reveal that participants are at high risk for clinically significant psychological/psychiatric 
issues.  If clinically significant findings are detected, parents will be notified and referred 
for psychological/psychiatric evaluation.  In the event that research personnel become 
aware of suicidal ideation on the part of any study participant, the following steps will be 
taken: (1) immediate consultation with Dr. Sara Williams, a licensed clinical psychologist 
(or other licensed clinical psychologist), (2) professional and confidential assessment of 
suicide risk and resources available, (3) immediate notification of the parent or legal 
guardian (if applicable), and (4) referral for appropriate services. It is important to note 
that data entry and evaluation of psychological questionnaires may be completed days 
or weeks after patient visits, but that these procedures will still be followed upon 
identification of suicidal ideation. 

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11.3 Confidentiality 
Investigators will take all reasonable measures to protect the confidentiality of 
participants and their families, including the following: 
Use of Participant ID Numbers: Each participant is assigned a participant identification 
number (SID).  All interview and research data are stripped of identifiers and labeled 
with the study number. The enrollment log with participant identifiers will be maintained 
in a secured, locked location available only to the study staff.  The participant’s name 
and any other identifying information will not appear in any presentation or publication 
resulting from this study. 
Deposition of Data into a Repository: Information from all psychological and sensory 
testing may be placed into a central data repository.  Data will be de-identified before 
submission to any central repository. Any photographs will be used only for mapping of 
pain in the current study, and not used for any other purpose. Only study personnel will 
be permitted to see the images. 
11.4 Potential Benefits 
The study may provide direct benefit to individual participants if our hypothesis is correct.  
The benefits are those to society as a whole in the improvement of knowledge of about 
spatial aspects of pain. 
11.5 Risk/Benefit Ratio and Importance of Information to be Obtained 
The risk/benefit ratio is favorable for this study and adverse events are not anticipated. 
The risk is minimal because all interventions can be terminated immediately. In addition, 
although an individual participant will not benefit from participation, the results of this 
study will make important contributions to the improvement of knowledge of the basic 
mechanisms of pain, the development of new diagnostic tests for pain, and ultimately in 
the improvement of treatment and prognosis of pain.  
11.6 Special Considerations for Minors 
Parents/guardians will not be permitted to remain in the room with their child during 
testing to avoid potential confounds.  However, parents will be allowed to view the area 
where the study procedures will occur and will then be escorted to a separate area when 
the study procedures take place. 
12. FUNDING 
Acquisition and analysis of data obtained from children is supported by startup funds 
provided by the Department of Anesthesiology. 

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13. REIMBURSEMENT/PAYMENT FOR STUDIES 
Participants or, in the case of children, the families will receive a pre-paid debit card 
immediately after they have provided consent. This card will be loaded with funds when 
the participant completes each visit (or withdraws from the study).  Patients will receive 
$30 at the end of visit 1, and $20 at the end of visit 2-9, and $30 at the end of visit 10. 
Healthy controls will receive $40 at the end of the Baseline visit. This payment scheme 
is in line with other ongoing studies in youth by our group.  
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