Carpometacarpal Osteoarthritis: Towards Identification of Biomechanical, Neuromuscular, and Somatosensory Mechanisms
Conditions: Carpometacarpal Osteoarthritis
Sponsor: University of Florida

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REFERENCE NUMBERS: 
IRB number: IRB201900693 
NCT# :  NCT04104477  
REDCap Record ID number: 403 
 
 
1. PROJECT TITLE 
 
Carpometacarpal Osteoarthritis: Towards Identification of Biomechanical, Neuromuscular, and 
Somatosensory Mechanisms 
 
 
2. INVESTIGATOR(S): 
 
Principal Investigator:  
Jennifer A. Nichols, Ph.D. 
 
Assistant Professor 
 
J. Crayton Pruitt Family Dept. of Biomedical Engineering 
 
Co-Investigators:  
Thomas Wright, M.D. 
 
Professor and Chief Hand & Upper Extremity 
 
Department of Orthopaedics 
 
 
Yenisel Cruz-Almeida, M.S.P.H, Ph.D. 
 
Assistant Professor 
 
Dept. Aging & Geriatric Research 
 
 
 
 
Other Study Personnel: 
Tamara Ordonez Diaz 
 
Ph.D. Graduate Student 
 
J. Crayton Pruitt Family Dept. of Biomedical Engineering 
 
 
3. ABSTRACT:  
 
This study examines carpometacarpal osteoarthritis (CMC OA). We specifically aim to elucidate the 
biomechanical, neuromuscular, and somatosensory mechanisms that contribute to CMC OA 
symptoms by using orthopaedic biomechanics and quantitative pain testing. Completion of this 
study will provide a comprehensive dataset describing how movement strategies (muscle activity 
and joint posture) as well as experimental and clinical pain differ between individuals with CMC OA 
and age-matched controls. 
 
 

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4.  BACKGROUND: 
Over 13 million Americans suffer from symptomatic hand OA.6 Involvement of the CMC joint at 
the base of the thumb (Fig. 1) is particularly disabling. Individuals with CMC OA can lose up to 
50% of hand function.2 Current conservative and surgical treatments do not provide the pain relief, 
strength, and mobility needed to restore both fine and gross motor function.7 Conservative 
treatments, such as physical therapy, orthoses, anti-
inflammatory drugs, and local steroid injection are effective 
for short-term pain relief, but offer minimal functional 
improvements.8, 9 Surgically treating CMC OA provides 
long-term pain relief, but has the unintended consequence 
of limiting mobility and strength.7 Unlike OA at the hip or 
knee, total joint arthroplasty is not standard of care for CMC 
OA.10 Instead, CMC OA is surgically treated with ligament 
reconstruction and/or bone excision.7 This translates into 
over eight different surgical options.3 No one surgery has 
proven superior and there is no consensus on how to 
choose between the surgical options.3 
Pain is the primary complaint in individuals seeking treatment for CMC OA. However, even though 
33% of postmenopausal women have radiographic evidence of CMC OA,5 only 5% of all women 
visit a doctor with painful symptoms.4 This heterogeneity of pain symptoms suggests there are 
pain phenotypes in CMC OA, similar to knee OA.11, 12 Importantly, the experience of pain results 
from a complex combination of sensory and cognitive processes that do not always clearly align 
with the underlying disease state.11, 13, 14 Studies using quantitative sensory testing (QST) to 
examine pain in CMC OA consistently conclude that CMC OA causes hyperalgesia, or increased 
sensitivity to painful stimuli.15-18 However, the mechanisms of hyperalgesia are unclear. Some 
studies suggest central sensitization changes in the dorsal horn in CMC OA,15, 17 while other 
suggest changes in peripheral sensitization occur.18 Further study is needed to identify the 
mechanisms of CMC OA pain that should be targeted clinically. 
Current treatments focus on modifying joint stability rather than directly addressing pain related 
symptoms. The focus on joint stability is widely supported by clinical studies theorizing that 
instability is a predisposing factor in CMC OA.19-22 A biomechanical study, however, recently 
challenged this theory by demonstrating that during typical activities joint stability is similar across 
individuals regardless of disease status.23 Importantly, this study assessed joint stability during 
active muscle contraction, whereas clinical studies typically assess joint stability through passive 
tests. Thus, muscle activity may play a critical role in modulating CMC joint stability and potentially 
symptom severity. To our knowledge, whether individuals with CMC OA can adapt altered muscle 
coordination strategies to mitigate symptom severity has not been directly studied. 
Clinically, there is a critical need for new treatments that provide long-term pain relief and more 
effectively restore fine and gross motor function in individuals with CMC OA. As a first step toward 
addressing this need, the contribution of this proposal 
is expected to be improved understanding of how 
biomechanical, neuromuscular, and somatosensory 
mechanisms influence symptom severity in adults with 
CMC OA. This contribution is significant as it directly 
addresses the primary barrier preventing the design of 
new, optimal treatments: the mechanisms that 
influence the severity of CMC OA have not been fully 
identified, and therefore cannot be clinically targeted.  
 
Figure 1. (A) The CMC joint connects 
the first metacarpal and trapezium. (B) 
X-ray of mild CMC OA from Ladd et al.1 
 
Figure 2. To alleviate CMC OA symptoms, 
we must understand multiple mechanisms. 

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5. SPECIFIC AIMS: 
Individuals with symptomatic thumb carpometacarpal osteoarthritis (CMC OA) can lose up to 50% 
of hand function.2 Surgical treatments aim to restore function and reduce pain by eliminating 
instability at the CMC joint. However, there are eight different surgeries commonly used, and no 
consensus on how to optimally choose between them.3 Treatment is also challenging because 
the presentation of symptoms is highly variable.4 For example, 33% of postmenopausal women 
have radiographic evidence of thumb CMC OA,5 yet only 5% of all women visit the doctor with 
symptoms.4 Some individuals may employ unique coping mechanisms that prevent development 
of pain and functional loss, while others may simply use over-the-counter medications to avoid 
the doctor. Regardless, very little is known about how an individual’s symptoms relate to the 
underlying osteoarthritic disease. My long-term goal is to design effective, targeted treatments for 
individuals with CMC OA. As a critical step toward this goal, the objective of this proposal is to 
elucidate the biomechanical, neuromuscular, and somatosensory mechanisms that occur during 
aging and contribute to the symptomology of CMC OA. This objective will be accomplished 
through two aims:   
Aim 1. Evaluate how muscle activity, joint kinematics, and CMC joint stability change in 
the presence of movement-evoked pain. Electromyography (EMG), joint kinematics, CMC joint 
stability, and movement-evoked pain during three functional tasks will be quantified in adults with 
end-stage CMC OA, age-matched controls, and young-healthy individuals. We hypothesize that 
greater levels of reported pain during task completion will be associated with increased muscle 
activity, larger joint angles, and decreased joint stability. Completion of this aim will quantitatively 
characterize biomechanical and neuromuscular mechanisms that influence CMC OA 
symptomology. 
Aim 2. Quantify the relationship between function, pain symptomology, and disease 
severity. Hand function, clinical and experimental pain, and disease severity will be measured in 
adults with end-stage CMC OA, age-matched controls, and young-healthy individuals. We 
hypothesize individuals with CMC OA will demonstrate greater functional deficits and higher 
experimental pain sensitivity than age-matched controls and young-healthy individuals. 
Additionally, in individuals with CMC OA, we hypothesize that functional loss will be associated 
with higher clinical pain, but not necessarily higher disease severity. Completion of this aim will 
comprehensively and quantitatively characterize the multi-faceted symptomology of CMC OA and 
provide insights into the somatosensory mechanisms affecting this disease. 
 
6. RESEARCH PLAN: 
 
Sample Size & Justification: A total of 60 subjects will complete the proposed research study: 20 
individuals with end-stage CMC OA, 20 age-matched controls, and 20 young-healthy individuals. 
These subjects will represent the racial and ethnic diversity of the state of Florida. Vulnerable 
populations including pregnant women and prisoners will be excluded. All subjects will be between 
the ages of 18 to 90. Specifically, the end-stage CMC OA cohort and age-matched controls will be 
between the ages of 40 to 90 as CMC OA is most prevalent in older adults. While the young-healthy 
cohort will be between the ages of 18-39. A power analysis (α = 0.05, 1-β = 0.80) to detect 20% 
differences in pinch strength between groups required 15 individuals per cohort. Due to including a 
young-healthy cohort and to prevent erroneous inferences to occurs after multiple comparisons, 20 
individuals per cohort will be recruited. Note, pinch strength was the only relevant variable for which 
standard deviations could be consistently estimated from the literature.23, 36 Thus, an important 
outcome of this pilot project will be the data necessary to robustly estimate sample sizes for future 
studies. For reference, prior studies indicate that individuals with early-stage CMC OA have 20-30% 
less pinch strength than controls.23, 36  
 

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A summary of inclusion and exclusion criteria are provided below: 
 
  
Inclusion Criteria:   
 
CMC OA Subjects: 
 
female between the age of 40 to 90 years 
 
end-stage CMC OA diagnosed by a board-certified clinician 
 
 
Age-Matched Control: 
 
female between the age of 40 to 90 years 
 
no joint or muscle pain in the hand or wrist 
 
Young-Healthy Subjects: 
 female between the age of 18 to 39 years 
 no joint or muscle pain in the hand or wrist 
 
Exclusion Criteria:   
All Groups: 
 
Pregnant women; minors (under age 18); mentally disabled; any persons 
incarcerated, on parole, on probation, or awaiting trial 
 
Individuals 
with 
concomitant 
musculoskeletal 
pathologies 
(other 
than 
osteoarthritis) in the hand or wrist, including distal radius fracture, contracture, 
trigger finger, and carpal tunnel 
 
Individuals with history of uncontrolled diabetes, rheumatoid arthritis, muscular 
dysfunction, or neurological disease 
 
Recruitment:  
The CMC OA subjects,age-matched control subjects, and young-healthy control subjects will be 
recruited, as described below: 
 
CMC OA Subject Recruitment: Subjects with CMC OA will be recruited directly from the 
hand clinics at the UF Orthopaedics Sports Medicine Institute (OSMI). Specifically, a clinical 
member of the study team affiliated with the Department of Orthopaedics (e.g., Dr. Wright) 
will identify individuals who meet the inclusion criteria. These individuals will be asked at the 
end of their clinic visit if they are interested in learning more about the research study and 
potentially participating. At this time, the potential participant’s contact information (name, e-
mail, phone number) and preferred contact method (phone or e-mail) will be recorded. A 
member of the IRB-approved study team will then reach out to the potential participant by 
phone or e-mail to discuss the study and answer any questions. If the potential participant 
expresses interest, he or she will be e-mailed a copy of the informed consent document to 
review and discuss with their friends and/or family. The study sessions will also be scheduled 
at this time. Subjects will be consented in-person at the time of their first study session.    
 
Age-Matched Control Subjects and Young-Healthy Subjects: Age-matched control 
subjects and young-healthy subjects will be recruited using the mechanisms listed below.  It 
should be noted that individuals with CMC OA may also contact the study team via these 
mechanisms.  However, the study team anticipates that these mechanisms will more readily 
identify age-matched control subjects: 
 
1) Recruitment Flyer – An IRB-approved recruitment flyer will be posted around the 
University of Florida’s campus and the Gainesville community in approved advertising 

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locations. The flyer will provide potential participants with the information necessary 
to contact the Study Team by phone and/or e-mail. 
 
2) Website Advertisement – An IRB-approved recruitment message will be posted on 
the Principal Investigator’s Lab Website (https://www.bme.ufl.edu/labs/nichols/get-
involved/) The recruitment message will provide potential participants with the 
information necessary to contact the Study Team by phone and/or e-mail. 
 
3) Word of Mouth – The Principal Investigator and Study Team frequently share results 
from completed studies through invited talks, guest lectures in undergraduate and 
graduate courses, and community events. When discussing our human subjects 
research, one of the most commonly asked questions is whether there are 
opportunities to become involved as a study participant.  Thus, we will share 
information about the study verbally with interested members of the community. 
When such verbal conversations take place, we will provide the potential participants 
with the information necessary to contact the Study Team by phone and/or e-mail. 
Scheduling and enrollment will occur at least 48 hours after the initial conversation 
and only after the potential participant has proactively contacted the Study Team. 
 
Initial Contact with Study Team: 
When a potential participant contacts the Study Team, we will follow-up with the potential participant 
by phone or e-mail.  During that discussion, we will ask the following questions: 
 
a) Are you a female between 18 and 90 years old? 
b) Have you been diagnosed with arthritis in your hand or wrist? 
c) Do you currently have muscle or joint pain in the hand or wrist? 
d) Have you had any muscle or joint pain in your hand or wrist requiring medical attention or 
physical therapy in the last 6 months? 
e) Are you currently pregnant, mentally disabled, incarcerated, on parole, on probation, or 
awaiting trial? 
f) Do you have any systemic musculoskeletal, neurological, or autoimmune diseases, such as 
diabetes, rheumatoid arthritis, or stroke? 
 
If a potential participant answers “yes” to question (a) and “no” to questions (b) – (f), then we will 
proceed with scheduling a study visit as an age-matched control subject.   
 
If a potential participant answers “yes” to question (a) – (b) and “no” to questions (c) – (f), then we 
will ask the following follow-up question: “What kind of arthritis have you been diagnosed with in 
your hand or wrist?”  If the answer is thumb OA, we will proceed with scheduling a study visit as an 
CMC OA subject. 
 
Otherwise, the potential participant will be informed that he or she is ineligible to participate.   
 
To facilitate continued communication and follow-up, we will ask the potential participant what his 
or her preferred method of contact is and will record his or her name, phone number, and e-mail 
address during these initial conversations. We will use the e-mail address to provide the potential 
participant with an electronic copy of the informed consent form to review prior to his or her first 
visit. This copy of the informed consent form will be provided to the subject at least 24 hours prior 
to their scheduled participation. All research subjects will be consented in-person at the time of their 
first study session.    
 

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Enrollment & Informed Consent: 
Prior to experimental data collection, each participant will be given the opportunity to review the 
informed consent form and study procedures in-person with a member of the study team.  This 
discussion will include information on study purpose and procedures, benefits and risks, who to 
contact (study team, IRB, etc.), that participation is voluntary and participants can withdraw at any 
time, HIPAA and confidentiality, as well as cost and compensation. The participant will be given the 
opportunity to ask questions.  After all questions have been answered, the participant will sign the 
informed consent form, documenting that they provide consent to participant as well as 
authorization to access their private health information as outlined on the informed consent form. 
 
Research Approach: 
The proposed human subject research will occur during three sessions. The first session (focused 
on biomechanics data for Aim 1) will include motion capture, electromyography (EMG), 
movement-evoked pain testing. This session is expected to last no more than 4-hours.  The 
second session (focused on somatosensory data for Aim 2) will include experimental pain testing, 
clinical pain testing, and clinical outcome measures. If needed, the clinical outcome measures 
can be completed in the first session as it is at no risk to the patient or the study. This session is 
expected to last 2-hours. The third session (medical imaging for Aim 2) will involve recording plain 
film radiographs. This session is expected to last less than 1-hour. Sessions can be scheduled 
consecutively on the same day or as separate study visits, based on the subject’s schedule and 
availability. Sessions can also be completed in any order. Detailed descriptions of each session 
is provided below: 
 
Session I – Biomechanics Testing Session (Collection of Data for Aim 1).  
Location: All biomechanics testing will occur in Dr. Nichols' Musculoskeletal Biomechanics 
Laboratory, located in Room 510 of the New Engineering Building (1064 Center Drive, 
Gainesville, FL 32611). This laboratory is specifically designed for biomechanical testing and 
human subject experiments.  It is a limited-access lab, meaning that only Dr. Nichols’ students 
and collaborators have access. All individuals with access have completed human subjects 
research training. During testing, only members of the IRB-approved Study Team will be 
involved in experimental data collection. A sign that reads “Experiment in Progress”  will be 
posted on the door during data collection to ensure subject privacy is maintained. 
 
Testing Procedures: All participants will be asked to wear short sleeve or sleeveless tops during 
testing. Participants will have the option to wear their own clothing or clothing provided by the 
lab. Participants will also be given the option to change into clothing in a private changing area 
after arrival at the lab. 
 
Upon arriving at the Musculoskeletal Biomechanics Lab, participants will be asked to provide 
basic demographic (age and sex) and anthropometric (height, weight, limb length) data.  
Following collection of this information, biomechanical data will be collected using skin-marker 
motion capture, electromyography (EMG), and movement-evoked pain testing.  
 
During testing, participants will be asked to perform range of motion tasks (e.g., circumduction 
of the CMC joint) as well as strength tasks (e.g., lateral pinch and opposition pinch) at varying 
effort levels (maximal and sub-maximal). Each task and effort level will be repeated at least 
twice. Skin-marker motion capture, EMG, and movement-evoked pain data will be collected 
during each task as described below: 
 
 
 
 

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Skin-Marker Motion Capture & Force Sensors 
Skin-marker motion capture involves placing reflective markers on palpable boney 
landmarks, such as the distal radial styloid. These reflective markers are secured to the 
subject’s skin using adhesive tape. Reflective markers will be placed across the hand and 
arm following the guidelines of the International Society of Biomechanics. Locations of the 
markers will be recorded during completion of the tasks using a 12-camera Vicon Vero motion 
capture system. During testing, the forces produced by the thumb will be recorded using 
custom force sensors. These data will provide a kinematic description of how the thumb, 
wrist, and arm move during the recorded tasks as well as kinetic data describing the forces 
produced. These data will also be used in the musculoskeletal simulations to calculate CMC 
joint contact forces. 
 
Intramuscular and Surface Electromyography (EMG). 
EMG uses surface electrodes (adhered to the skin) and/or intramuscular electrodes (fine wire 
needles inserted into the muscle belly) to measure muscle activity. The thumb is controlled 
by 9 muscles: 4 extrinsic muscles [extensor pollicis brevis (EPB), extensor pollicis longus 
(EPL), abductor pollicis longus (APL), and flexor pollicis longus (FPL)] that have their muscle 
bellies located in the forearm and 5 intrinsic muscles [oblique and transverse heads of the 
adductor pollicis (ADPo and ADPt), abductor pollicis brevis (APB), opponens pollicis (OPP), 
and flexor pollicis brevis (FPB)] that have their muscle bellies located in the hand. These 
muscles will be recorded using intramuscular EMG. Up to ten additional muscles may be 
recorded using surface EMG. All intramuscular electrodes will be placed by a trained 
researcher following standard practice guidelines. Specifically, the insertion site will be 
cleaned with alcohol and the fine wire needle electrodes will be inserted using a disposable, 
sterile needle.  When the needle is withdrawn, the two fine wire electrodes (roughly the 
thickness of a human hair) will remain in the muscle belly. Electrode wires will be secured to 
the skin with tape to prevent unintended removal. All electrodes will be removed at the end 
of data recording. Ultrasound imaging and muscle stimulation, the standard techniques for 
ensuring appropriate electrode placement, will be used to verify that the electrodes have 
been placed in the correct muscles. No more than three insertion attempts will be made for 
any single muscle. If after three attempts, the electrode cannot be placed, we will not record 
from that muscle.  Subjects will be instructed that they may choose to stop placement of 
intramuscular electrodes at any time, and reminded of this fact during placement of 
intramuscular electrodes. All surface electrodes will be placed in accordance to the 
guidelines established by the European Recommendations for Surface Electromyography 
(SENIAM) and the International Society of Electrophysiology and Kinesiology (ISEK). Unlike 
intramuscular electrodes, surface electrodes are adhered to the skin like stickers and record 
from superficial muscles, such as the ECRL. All EMG signals will be recorded using a Delysis 
Trigno EMG system, which is synched with the Vicon system to allow simultaneous recording 
of muscle activity, kinematic data, and kinetic data. The collection of EMG data is important 
because muscle activity measured in vivo will be used to understand whether individuals use 
different muscles to perform specific activities given their condition (i.e., CMC OA versus age-
matched controls). 
 
Movement-Evoked Pain. 
Movement-evoked pain testing requires subjects to provide a self-reported pain level before, 
during, and after each task. For this study, we will use the Visual Analog Scale (VAS) to 
record movement-evoked pain. Movement-evoked pain levels will be used to understand 
whether differences in pain severity exist between the maximal and sub-maximal effort tasks 
and to also evaluate how various pain levels affect the movement strategies (i.e., muscle 
activity recorded via EMG and joint angles recorded via motion capture).  

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Session II – Somatosensory Testing Session (Collection of Data for Aim 2)  
Location: Somatosensory testing, which involves quantitative sensory testing (QST) and 
completion of questionnaires, will be completed in the Pepper Center Institute on Aging in 
the Clinical Translational Research Building (CTRB) or the Dental Tower. Location will be 
determined in advance based on availability and scheduling of the equipment necessary for 
QST. The space and equipment needed for QST is available to Dr. Cruz-Almeida (co-
Investigator), who has extensive experience with these study procedures. 
 
Testing Procedure: Through a combination of quantitative testing and self-reported 
assessments, data on experimental pain, clinical pain, hand function, and disease severity 
will be reported. Details on the methods used are provided below.  
 
Quantitative Sensory Testing (QST). 
QST involves systematically exposing individuals to stimuli in order to detect their pain 
threshold. Mechanical (i.e., pressure) and thermal stimulation will be used in this study. QST 
will be performed in standardized sites using anatomical landmarks. All tests will be 
demonstrated and explained prior to being performed. All participants will be tested on the 
extremities. For participants with pain, additional standardized testing sites will be chosen to 
include painful areas. The “TSA Thermal Sensory and Vibratory Sensory Analyzer (Model 
TSA II, VSA 3000) (Medoc. LTD)” will be used in this study to quantify nerve fiber dysfunction 
with measurements of vibratory, pinprick and thermal sensory thresholds (warm, cold, heat-
induced pain, and cold-induced pain). A hand-held algometer (FDX, Wagner Instruments 
and/or Algomed, Medoc.LTD) will be used to assess pressure pain sensitivity. Prior to testing 
we will obtain skin temperature readings at all testing sites by using the DT1001 DermaTemp 
infrared scanner (Exergen). Similar procedures have been used by us and other investigators 
in older adults with and without pain. 
a. Vibratory Detection Thresholds: Vibratory threshold is tested with a vibratory pin, which 
presses the measured area with a consistent pressure of 50g. The vibratory sense analysis 
will be performed using upward-moving stimulus (increasing in intensity until a sensation is 
perceived). Several vibrations will be given sequentially and the mean end variance will be 
determined to verify the consistency of the test. 
b. Tactile Detection Thresholds: Thresholds for light touch will be assessed with von 
Frey monofilaments, using two ascending and two descending stimulus series, according 
to the method of limits. Detection threshold at each test site will be determined by the 
obtaining the geometric mean across these four test series.  
c. Thermal Detection Thresholds, Pain Thresholds and Temporal Summation: 
Following a brief introduction familiarizing each subject with the procedure, several trials 
will be performed for each sensory modality and a mean threshold will be calculated. For 
threshold determination we will use a “reaction time-inclusive” method, the method of 
limits, consisting of continuously changing intensities of stimuli halted automatically by the 
subject at the moment that the requested sensation is perceived. The following thresholds 
will be evaluated using the TSA II: (1) cool sensation; (2) warm sensation; (3) cold pain; 
and (4) heat pain. Subjects will also be asked to rate the painful sensation. Temporal 
summation of heat pain may be assessed by administering brief repetitive suprathreshold 
heat stimuli to the hand. 
d. Allodynia and Temporal Summation: Dynamic mechanical allodynia will be 
investigated using a soft brush and lightly brushing the skin of the hands and feet as well as 
any reported painful areas. If pain is evoked in the test area, the participant will be asked to 
rate the intensity of the pain. If an allodynic area is detected, temporal summation will be 
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Hz for 10 seconds. If temporal summation is evoked in the allodynic test area the participant 
will be asked to rate the intensity of the pain. 
e. Punctate Pain Testing and Temporal Summation: We will apply punctate mechanical 
stimuli to the test sites with a series of weighted probes. Probes of different weights will 
be applied to participants’ skin to determine the level that produces slight discomfort or 
pain. Two measures are obtained: 1) Pain threshold is determined by applying probes of 
different weights in ascending and descending sequences and participants are asked to 
tell the examiner which probes produce pain; 2) A weighted probe is applied either once 
or several times in a row and participants are asked to rate the pain they experience from 
the probe. In addition, a standardized plastic MediPin commonly used in neurological 
examinations will be applied to testing areas and participants will be asked to rate the 
intensity of any pain that is experienced. 
f. Pressure Pain Thresholds: Pressure is delivered by a hand-held algometer (spring-
controlled device delivering calibrated pressure via a flat 10mm diameter rubber tip). 
Pressure is delivered at an approximate rate of 1 kg/sec. Participants respond when they 
first feel pain, at which time the pressure is removed.   
 
Clinical Pain & Psychological Measure. 
Clinical pain will be assessed through questionnaires, including the Graded Chronic Pain 
Scale (GCPS), pain experience questionnaire (OPTIMIZE Pain Experience FITT), a 
comprehensive pain history (OPTIMIZE Health History), SF-36 - Short Form Health Survey, 
Brief Pain Inventory, PainDetect and the Australian Canadian OA Hand Index (AUSCAN). 
Psychological measures will also be assessed using the PROMIS Anxiety and Depression 
short forms, Center for Epidemiologic Studies Depression Scale (CES-D), Beck Depressive 
Inventory (BDI), Perceived Stress Scale (PSS), Montreal Cognitive Assessment (MoCA), 
Coping Strategies Questionnaire – Revised (CSQ-R), Satisfaction with Life Scale (SWLS), 
the Revised Life Orientation Test (LOT-R), and the Positive and Negative Affect Sale 
(PANAS). 
 
Together, these assessments will provide insights into each subject’s clinical pain 
experience. Specifically, the GCPS yields a “Characteristic Pain Intensity” score and an 
overall “Disability” score providing insight into global pain severity and pain-related 
interference over the past 6 months.  The comprehensive pain history provides an index 
measure of important pain domains associated with biological aging ad functioning. These 
domains are frequency, intensity, time (duration) and total pain sites. The AUSCAN assesses 
disease-related pain and is specifically designed for hand OA. The PROMIS Anxiety and 
Depression short forms, CES_D, and BDI screen for symptoms of mood disturbance and has 
been extensively validated in chronic pain populations such as OA. The MoCA evaluates 
different types of cognitive abilities. The CSQ-R uses a pool of items that reflect coping 
strategies frequently reported by patients and proven to be important in the management of 
pain. The LOT-R measures how optimistic or pessimistic people feel about the future which 
has been shown to correlate with people’s health, work performance, and educational 
attainment. The PANAS will report how individuals generally feel with positive affect reflecting 
enthusiasm and negative affect reflecting distress. Subject’s response to questions regarding 
risk of suicide will be reviewed immediately after the study. If a subject or potential subject 
indicates suicidal thoughts or wishes, the principal investigator of the study, Dr. Nichols, and 
a representative the UF Psychology Clinic, Dr. Dawn Bowers (or their appropriate 
designees), will be informed. In the unexpected event that Dr. Bowers, nor their designees 
are available, the Alachua Country Crisis Center will be contacted. The clinical pain metrics 
will be primary outcome variables of the study. The psychological measures will be used as 
possible covariates and support future studies that more comprehensively include 

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psychological measures. Subjects will be given ample time to complete all questionnaires 
and provided with the opportunity to ask questions about any and all measures. The 
questionnaires can be completed by the subject in any session (Session I or Session II) as 
needed. 
 
Functional Outcome Measures. 
Participants will perform range of motion (thumb only) and strength (pinch and grip) tests as 
well as the Jebsen Hand Function test, which includes seven timed activities to evaluate fine 
and gross motor function. Participants will also complete the Disability of arm, shoulder, hand 
(DASH) score, a widely used functional outcome measure for the upper limb. Together, these 
measures were chosen to provide insights into strength, range of motion, as well as fine and 
gross motor function.  
 
Session III – Medical Imaging Session (Collection of Data for Aim 2)  
Location: Plain film radiographs will be collected at the Orthopaedic Sports Medicine Institute 
(OSMI) located at 3450 Hull Road.  
 
Testing Procedure: Plain film radiographs will be acquired to assess disease severity. 
Acquisition methods will be similar to those used for clinic patients:  
 
Plain Film Radiographs. 
For each subject, radiographs will be acquired from two views: anteriorposterior (Robert 
view) and lateral view. For the CMC OA subjects, if the x-ray views required for this study 
have been acquired as part of a standard clinical visit in the last 1 month, new x-rays will not 
be acquired as part of the study. Instead, x-rays will be obtained from the subject’s medical 
record, following informed consent and approval. A certified UF Health technician will acquire 
the films. According to RadiologyInfo.org, an information service sponsored by the 
Radiological Society of North America (RSNA) and the American College of Radiology 
(ACR), an x-ray of an extremity (such as the hand or foot) has an approximate radiation dose 
of 0.001 mSv, which is equivalent to approximately 3 hours of natural background radiation 
(https://www.radiologyinfo.org/en/info.cfm?pg=safety-xray).  Given that this study will require 
two x-rays, we estimate the approximate radiation dose as 0.002 mSv, or the equivalent of 6 
hours of natural background radiation. The radiographs will be used to classify the presence 
of CMC OA using the Eaton classification method and the Hand OA Index. The control 
subjects will be recruited based on lack of pain and disability. These asymptomatic subjects 
may have evidence of CMC joint degeneration, which will be an important covariate in the 
analyses. The severity of CMC OA within the CMC OA participants will also be important for 
analyzing the experimental and clinical pain as well as functional measures in the context of 
disease severity. 
 
Participants will be given the option during the informed consent process to consent to photographs, 
videos, and/or audio recordings. If the individual does not consent, photographs, videos, and/or 
audio recordings will not be collected. The primary purpose of collecting photographs, videos and/or 
audio recordings is to aid in analysis and interpretation of data.  If consent is given, these items may 
also be used for educational purposes at the University of Florida or in presentations and 
publications beyond the University of Florida. Collected photographs and video recordings will only 
be used in ways approved by the subject.  In all presentations and publications, identifiable features 
(defined as unique tattoos or skin markings and/or any aspect of the subject’s face) will be removed 
from displayed images. 
 
 

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Data Storage 
Research data collected from the human subjects will include skin marker motion capture data, 
EMG, movement-evoked pain measures, QST data, clinical pain and psychological measures, 
function outcome scores, and radiographs. Data will be used only for research purposes. Only 
the subject’s age, sex, and a subject specific code will be documented with the data. The 
information linking the subject specific code to private health information will be stored securely 
in a locked cabinet within Dr. Nichols’ laboratory and/or electronically on a HIPAA compliant, 
password-protected server at the University of Florida. Only IRB approved research personnel 
will have access to identifiable research data. Analysis of research data will be completed on 
password protected computers. All identifying information will be removed from digital radiographs 
prior to publication, presentation at conferences, or discussion of the images with persons other 
than those listed as study personnel. HIPPA compliance will be strictly maintained.  
Additionally, the names, visit numbers, and MRNs of each study subject will be included 
with the digital radiographs on the University of Florida PACs system, as required by the University 
for auditing purposes. Only trained personnel will retrieve digital radiographs of subjects from the 
database, as they are required to do so as part of their normal job duties. 
All research personnel will complete annual training for human subject protection and 
HIPAA/confidentiality in compliance with University of Florida guidelines. 
 
7. Possible Discomforts and Risks: 
Most of the experimental procedures involved in this study have no greater than minimal risks. 
However, intramuscular electromyography (EMG), which involves insertion of fine wire needle 
electrodes, poses slightly more than minimal risk.  All procedures are described below: 
 
Activities Performed During Motion Capture. Participation in the motion capture study 
should not cause pain or discomfort beyond what is experienced in routine, daily life or a 
standard clinical evaluation during a visit to the doctor. Nonetheless, we will exclude research 
subjects who are unwilling or unable to perform the activities to ensure that it poses no 
substantial additional risk or causes no substantial pain to our subjects. 
 
Skin-Marker Motion Analysis. Skin-marker motion analysis poses minimal risk to subjects. 
Reflective markers are secured to the skin using adhesive tape. Removing this tape may 
cause mild discomfort or skin irritation (i.e., redness). This discomfort is similar to that 
experienced when removing a bandaid. 
 
EMG. Surface EMG poses minimal risk. The only known health risk is mild discomfort or skin 
irritation (i.e., redness) associated with removal of the surface electrodes. Rare, but possible 
risks of intramuscular (or fine wire) EMG include inflammation, infection, bleeding, and/or 
fainting. Damage to nerve or blood vessels form the wire is also possible, although rare. Mild 
discomfort associated with placement of the intramuscular EMG electrode is possible. We will 
minimize risks by having only trained research staff insert intramuscular electrodes. 
Ultrasound guidance will also be utilized to assist with needle placement around sensitive 
anatomy. Additionally, subjects will be given the option of stopping needle insertion at any 
time. Subjects will be fully compensated for the biomechanics session, even if they choose to 
stop EMG needle insertion prior to all electrodes being placed. 
 
Quantitative Sensory Testing. QST is generally considered safe. However, participants will 
experience some pain or discomfort. Due to the pressure pain procedure (mechanical stimuli), 
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 thumb, though this is expected to be brief in duration.  Also, this risk is diminished 

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by applying brief stimuli well below the participant’s tolerance level. Due to the thermal stimulation 
procedure, there is a slight change of burning the skin. However, this risk is diminished by 
carefully monitoring the stimuli levels. The risk of burn injury as a result of overheating contact 
thermode due to technical malfunction is very unlikely because the subject: (1) is free to withdraw 
from the thermode; (2) has the option to stop the stimulus at any point.  In addition, the stimulator 
incorporates automatic safety features that do not depend on actions of the investigator or 
subject: (3) a safe range (max 520C) is programmed into the system preventing accidental use 
of potentially harmful temperature set-points; (4) the software continuously monitors thermode 
temperature and automatically interrupts thermode contact with the skin when the process value 
exceeds the set-point by >1.00 C. 
There is also a minor risk of psychological discomfort due to QST. The prospect of being 
subjected to painful stimulation in an unfamiliar location, surrounded by unfamiliar investigators 
and equipment that may look intimidating may lead to anxiety.  We try to minimize this anxiety 
by thoroughly explaining all procedures and taking the time to answer all questions the participant 
might have.  We make sure that ample time is scheduled for the first session, so the participant 
does not feel rushed and has time to get to know the lab environment and investigators.  In 
addition, we allow the participant to experience a few sample stimuli before deciding whether or 
not to go ahead with the actual testing.  Our tests always start with a few non-nociceptive stimuli 
before the temperature rises gradually.  In spite of these measures we cannot completely rule 
out that some participants may feel some anxiety during the first session.  However, based upon 
experience in other studies using similar protocols, we are confident that most subjects will not 
experience psychological stress during the second and subsequent sessions, when they have 
become familiar with the experimental setting. 
 
Clinical Pain, Psychological, and Function Measures: The questionnaires and functional 
tasks proposed in this study are considered minimal risk. Some individuals may feel 
unconformable with some questions. Notably, the PROMIS short for screening for anxiety and 
depression may indicate that a research subject is anxious or depressed. These forms will be 
scored prior to the completion of the session. An elevated score, meaning an individual is 
anxious and/or depressed will be handled by contacting one of the clinical co-Investigators 
(Sibille or Wright) and obtaining the appropriate referrals.   
 
Radiation Exposure. There is an extremely small chance that research subjects will be more 
susceptible to developing cancer because of increased exposure to radiation experienced 
during the radiographs required for this study. However, the risk due to exposing the hand, a 
distal segment that is not close to vital organs, to the radiation from an x-ray is extremely low. 
The Food and Drug Administration (FDA) Guidelines for Research Subjects sets an estimated 
dose equivalent (EDE) limit of 3 rem for a single session and no more than 5 rem annually. 
The total EDE associated with participation in this study is estimated to be less than 2 mrem 
(note the difference in units). This is less than 1 percent of the amount of background radiation 
that the average person in the United States receives each year (annual background radiation 
estimated to be 0.36 rem).  
 
Additional Protections Against Risk: 
The study design provides several measures to minimize the potential risks to subjects: 
 
Minimizing Risks to Privacy by Protecting Confidentiality: The collected PHI includes, 
age and biological sex. This information will only be identifiable by a subject specific code. A 
document linking the subject specific code to the name of the subject will be stored securely 
in a locked cabinet within Dr. Nichols’ laboratory and/or electronically on a password-protected 

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server in the University of Florida. Only IRB approved research personnel will have access to 
identifiable research data. 
 
Minimizing Risks by Using Qualified Study Personnel 
We will also protect subjects by having appropriately trained personnel perform/oversee the 
necessary procedures. The radiographs will be acquired at UF Health in a manner identical 
to that used on patients, such that privacy and safety will be ensured. Trained and qualified 
technicians employed by the University of Florida will obtain all scans. 
Motion analysis and EMG testing (Session I biomechanics testing) will take place in Dr. 
Nichols Musculoskeletal Biomechanical Laboratory in the J. Crayton Pruitt Family Department 
of Biomedical Engineering. Only trained members of the research team will operate the motion 
capture and EMG systems. Dr. Nichols has received training on insertion of fine wire EMG 
electrodes through the Gait & Clinical Movement Analysis short course. This training fulfills 
the classroom training requirements for clinicians and researchers in California, the state with 
the strictest fine wire EMG electrode laws. All fine wire needle electrodes will be placed 
following best practices to ensure safety and sterility.  
The experimental pain procedures (Session II somatosensory testing) described in this 
application are widely used and safe.  While they produce pain, risks to the subjects are minimal, 
because:  
1) the pain is transient in nature, and generally subsides immediately after the procedure; 
2) subjects are instructed that they may stop any procedure at any time with no adverse 
consequences; and  
3) the level of pain experienced by subjects is below their tolerance level. 
 
Dr. Cruz-Almeida, who has extensive experience with experimental pain testing, and Dr. Sibille, 
who has extensive experience with clinical pain testing, will ensure all pain testing is completed 
in a safe and appropriate manner. Risks will also be minimized by adhering to our exclusion 
criteria, and the study physician (Dr. Wright, co-mentor) will have full discretion to exclude 
participants for whom they feel there is excessive risk for participation. 
 
8. POSSIBLE BENEFITS: 
 
There are no direct benefits to subjects for participating in this study. However, the knowledge gained 
from this study will benefit society by providing new information regarding the mechanisms 
underlying CMC OA pain and disability.   
 
The contribution of this proposal is expected to be improved understanding of how biomechanical, 
neuromuscular, and somatosensory mechanisms influence symptom severity in adults with CMC 
OA. This contribution is important as it directly addresses the primary barrier preventing the 
design of new, optimal treatments: the mechanisms that influence the severity of CMC OA have 
not been fully identified, and therefore cannot be clinically targeted. The data collected from this 
study will also form the foundation for future work on CMC OA phenotypes.  Thus, this study will 
enable future design and development of effective, targeted treatment for CMC OA. 
 
 
9. CONFLICT OF INTEREST: 
 
The investigators do not have any conflicts of interest 
 

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