Neuropathic Pain in Pregnancy
Phase: NA
Conditions: Pain, Pregnancy
Sponsor: University of Arkansas

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 1 of 19 
 
Neuropathic Pain in Pregnancy 
Protocol # 204737 
ClinicalTrials.gov ID: NCT02608463 
Principal Investigator: Shona L. Ray-Griffith, MD1,2 
Assistant Professor 
 
 
Co-Investigator: Jessica Coker, MD1 
 
Medical Monitor: Michael Mancino, MD1 
 
 
 
1Department of Psychiatry 
4301 W. Markham St., Slot 843-A 
Little Rock, AR 72205 
 
2Department of Obstetrics and Gynecology 
4301 W. Markham St., Slot 518 
Little Rock, AR 72205 
 
 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 2 of 19 
Abbreviations: 
a) AED = anti-epileptic drugs 
b) BDI = Beck Depression Inventory 
c) CGI-I = Clinical Global Impression-Global Improvement Scale 
d) EFNS = European Federation of Neurological Societies 
e) IASP = International Association for the Study of Pain 
f) neuPSIG = Neuropathic Pain Special Interest Group 
g) NP = neuropathic pain 
h) NSAID = non-steroidal anti-inflammatory drug 
i) PCP = phencyclidine  
j) PCS = Pain Catastrophizing Scale  
k) PDQ = painDETECT Questionnaire 
l) PGIC = Patients’ Global Impression of Change scale 
m) PRI = Psychiatric Research Institute 
n) PROMIS = Patient Reported Outcomes Measurement Information System 
o) rTMS = repetitive transcranial magnetic stimulation 
p) TCA = tricyclic antidepressant 
q) THC = tetrahydrocannabinol 
r) TMS= transcranial magnetic stimulation 
s) UAMS = University of Arkansas for Medical Sciences 
t) UWC = University of Arkansas for Medical Sciences Women’s Clinic 
u) VAS = Visual Analogue Scale 
v) WMHP = Women’s Mental Health Program 
 
 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 3 of 19 
Introduction – Background 
Neuropathic pain (NP), defined as ‘pain initiated or caused by a primary lesion or dysfunction in 
the nervous system’ according to The International Association for the Study of Pain (IASP), 
affects up to 8% of the population (IASP Task Force; Dieleman et al 2008). Compared to other 
chronic pain conditions, NP is associated with higher pain severity, poorer health, and greater 
disability (Smith et al 2007). In addition, depression and anxiety are common comorbidities of NP 
(Radat et al 2013). As NP affects more women than men (Dieleman et al 2008), women’s health 
practitioners need to be familiar with both acute and chronic neuropathic pain conditions. Acquired 
nerve compressions are common in pregnancy, and consensus exists regarding their 
management (Sax and Rosenbaum 2006). However, knowledge regarding chronic NP (and other 
chronic pain conditions) in pregnancy is scarce. The overall goal of this project is to better 
define the course, management, and obstetrical/neonatal outcomes of chronic 
neuropathic pain in pregnancy and the acute postpartum period. 
 
Acquired nerve compressions peak in the third trimester and the majority resolve by six months 
postpartum. The trend of chronic NP as well as chronic pain in pregnancy is unknown. This study 
will characterize the course of neuropathic pain in pregnancy and the postpartum period 
using longitudinal measures of pain characteristics. 
 
Pharmacological management of NP is suboptimal as those with NP report greater disability and 
less effective pain relief despite receiving more pain medication prescriptions compared to those 
with non-neuropathic pain (Torrance et al 2007; Smith et al 2007). In addition, pharmacological 
treatment fails to relieve symptoms at the costs of side effects (e.g., constipation, dry mouth, 
sedation, risks of falls). Thus, alternative pharmacological treatments or non-pharmacological 
options are needed. 
 
Neurostimulation modalities are efficacious in the management of NP but are not included in 
current treatment guidelines (O’Connor and Dworkin 2009; Attal et al 2010; Moulin et al 2007). In 
particular, rTMS is one technique that has shown effectiveness in the management of NP and is 
recognized as having level B evidence (Hosomi et al 2013; Khedr et al 2005; Mhalla et al 2011; 
Passard et al 2007; Onesti et al 2013; Cruccu et al 2007). Transcranial magnetic stimulation uses 
electromagnetic induction to influence underlying cortical neurons and trigger action potentials. 
This non-invasive and localized mechanism of action makes it attractive for use in special 
populations, such as pregnancy. 
 
Pain management in pregnancy relies on conservative strategies and pharmacological 
monotherapy to minimize the risk to benefit ratio of fetal exposure; thus, the management of NP 
in pregnancy is challenging as evidence of teratogenicity limits options. In addition, little is known 
of other treatment options, such as pregabalin and duloxetine (Hoog et al 2013; Winterfield et al 
2015). Also, pharmacological monotherapy is always recommended to minimize fetal exposure 
in pregnancy, and this limits the use of combination therapies. 
 
Transcranial magnetic stimulation may be an acceptable alternative to pharmaceuticals for the 
management of NP in pregnancy. Repetitive transcranial magnetic stimulation is acceptable as a 
treatment option for depression in pregnancy (Kim et al 2011). Two studies effectively applied 
rTMS in pregnancy for depression with no adverse fetal or obstetrical outcomes (Sayar et al 2014; 
Kim et al 2011). According to a follow-up study, rTMS is not associated with poorer cognitive, 
motor, or language development in children of mothers who were treated with rTMS in pregnancy 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 4 of 19 
for depression (Eryilmaz et al 2014). This will be the first pilot study to investigate the use of 
rTMS in the treatment of neuropathic pain in pregnancy. 
 
The application of rTMS in pregnancy for the treatment of depression has resulted in two cases 
of inferior vena cava compression syndrome (also referred to as supine hypotensive syndrome) 
and one episode of dizziness without hypotension (Kim and Wang 2014). This condition typically 
occurs after 24 weeks gestation and is managed by placing the pregnancy women onto the left 
lateral position if they are going to be supine for an extended period of time. Thus, it has been 
recommended to avoid the supine position when applying rTMS to the pregnant women (Kim and 
Wang 2014). To decrease the likelihood of inferior vena cava compression syndrome, all subjects 
beyond 24 weeks gestation will be positioned on their left side using a wedge cushion. 
 
Seizures can adversely affect pregnancy, and the use of high frequency stimulation, defined as 
greater than or equal to 10-Hz, in rTMS increases the risk of seizures. The general risk of seizures 
with rTMS is low (1/10,000), and rTMS has been used in pregnancy at high frequency (I.e. 25-
Hz) stimulation without any adverse effects (Sayar et al 2014). The proposed study will utilize 5-
Hz as it is the lowest, effective frequency stimulation reported for the treatment of neuropathic 
pain (Hosomi et al 2013). We believe this will minimize seizure risk, and in efforts to further 
decrease seizure risk with rTMS, the study is applying rTMS in trains of pulses interspersed with 
periods of rest and excluding those with risk factors for seizures. The results of the current study 
will provide data supporting the acceptability and feasibility of rTMS of the treatment of 
neuropathic pain in pregnancy and will support larger studies to determine the most effective and 
safe frequency stimulation for the treatment of neuropathic pain in pregnancy. 
 
The management of chronic pain conditions in pregnancy has a direct effect on neonatal 
outcomes through fetal exposure. For example, neonatal abstinence syndrome is a drug 
withdrawal disorder of neonates that is secondary to in utero exposure to opioids, 
antidepressants, and muscle relaxants – all which are used to treat NP. Given the current limited 
knowledge of teratogenicity regarding pharmacological agents, we aim to better define the 
association of neonatal outcomes with chronic neuropathic conditions in pregnancy. We aim to 
compare obstetrical and neonatal outcomes of pregnant women with neuropathic pain, 
non-neuropathic pain, and no pain. 
 
Objectives 
To further define the impact of NP in the peripartum period, we propose the following objectives: 
I. 
Characterize the course and pharmacological management of neuropathic pain in 
pregnancy and the postpartum period. We will define descriptive statistics of the use of 
analgesic medications in pregnancy and the postpartum period for the treatment of 
neuropathic pain. 
II. Compare obstetrical and neonatal outcomes of pregnant women with chronic neuropathic 
pain, non-neuropathic chronic pain, and pregnant women without chronic pain. 
III. Determine the acceptability and tolerability of rTMS for the treatment of neuropathic pain in 
pregnancy, and describe the impact of rTMS on neuropathic pain in pregnancy. 
 
Subject Selection 
Subjects will be enrolled through the Women’s Mental Health Program (WMHP) at the University 
of Arkansas for Medical Sciences (UAMS) at the following clinical spaces: Psychiatric Research 
Institute (PRI); UAMS Women’s Clinic (UWC); the Psychiatric Research Institute (PRI) inpatient 
units (PRI floors 5&6); and the UAMS Obstetrics & Gynecology units (UAMS floors 5,6, and 7A). 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 5 of 19 
Study visits can occur at all of the above locations. For those subjects in part B, study visits will 
occur in a designated room designed for rTMS in the PRI. We aim to actively recruit and enroll 60 
pregnant women and up to 70 infants (to allow for multiple gestation pregnancies) for Part A of 
this study and enroll 10 pregnant women and up to 15 infants (to allow from multiple gestation 
pregnancies) (from Part A) for Part B. 
 
Compensation: Mothers participating in the study will receive a $10 in cash for each visit.  
All participants will be given a token or voucher to pay for parking at each outpatient study visit 
when applicable. 
 
Inclusion of Women, Minorities and Children 
Women and adolescents between 18-45 years of age are eligible for participation in the current 
study. Every effort will be made to recruit a diverse population of women along racial and ethnic 
categories residing in underserved areas. 
 
Eligibility Criteria 
All women will provide consent and HIPAA authorization prior to enrollment in the study. 
 
Part A: 
Maternal Inclusion Criteria 
• 
Age 18-45 years old, 
• 
Ability to give informed consent, 
• 
Viable pregnancy, and 
• 
Enrollment prior to or equal to 24 weeks gestation 
 
Maternal Exclusion Criteria 
• 
Active or history of substance use disorder within the past year 
• 
Non-English speaking 
 
Part B: 
Maternal Inclusion Criteria 
• 
Subjects enrolled in Part A and willing to consent to Part B of this protocol 
• 
Pregnant with current chronic neuropathic pain 
• 
Subjects failed treatment with amitriptyline or nortriptyline as defined by one of the following: 
o no clinical improvement following a four week trial of amitriptyline or nortriptyline (i.e., 
CGI-I score ≥4) 
o an inability to tolerate the medication (i.e., side effects) 
• 
Subjects must pass the TMS Safety Checklist Adult Safety Screen (TASS). 
• 
Subjects should be off medication, which can lower seizure thresholds (e.g., amitriptyline 
and nortriptyline) for at least two weeks prior to study entry. 
• 
Subjects with neuropathic pain including those with diagnosis of spinal cord injury, 
fibromyalgia, compression neuropathies (including diabetic peripheral neuropathy), post 
stroke pain, and multiple sclerosis 
• 
Subjects with a baseline VAS score greater than 30 
 
 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 6 of 19 
Maternal Exclusion Criteria 
• 
Current or past history of a seizure disorder (e.g., epilepsy) 
• 
Current history of preeclampsia 
• 
Current or history of brain lesions (e.g., aneurysm) 
• 
History of major head trauma (e.g., stroke; previous cranial neurosurgery) 
• 
Ferromagnetic metal in the head, neck, or chest (e.g., plates or pins, bullets, shrapnel) 
• 
Microprocessor implants in the head (e.g., cochlear implants) or life-sustaining 
microprocessor implants anywhere in the body (e.g., prosthetic cardiac valves) 
• 
Cardiac pacemaker 
• 
Active or inactive implants (e.g., deep brain stimulators, vagus nerve stimulators) 
• 
Active treatment with medications that lower seizure threshold (e.g., bupropion, 
amitriptyline, nortriptyline, or other TCA) 
• 
Increased intracranial pressure (which lowers seizure threshold) 
• 
Implanted medication pumps 
• 
Intracardiac lines 
• 
Significant heart disease defined as heart disease that causes moderate to severe 
symptoms and/or is characterized by moderate to severe pathology, including a recent 
history of myocardial infarction and heart failure with an ejection fraction of less than 30% 
or with a New York Heart Association Functional Classification of Class III or IV. 
• 
Bipolar disorder (to reduce the risk of mania) 
• 
History of suicide attempt(s) 
• 
Family history of epilepsy 
• 
Heavy alcohol consumption within the past 48 hours 
• 
Permanent makeup or tattoos with metallic dyes 
 
Investigational Plan 
The study will involve two phases - initially focusing on identification and course, followed by 
treatment paradigm assessment (Part A), and culminating in a pilot trial of rTMS (Part B). 
 
Part A: 
Study visits will occur approximately every 4-6 weeks during pregnancy until approximately 3 
months postpartum for a maximum of 12 visits. Table 1 provides an overview of study procedures. 
Figure 1 illustrates subject participation and flow. In order to optimize diagnostic clarity for group 
assignment, we will employ a valid tool, the painDETECT Questionnaire (PDQ), for diagnostic 
purposes (written permission for use of PDQ has been obtained and is available upon request). 
The PDQ has been validated and shown high sensitivity (85%), specificity (80%), and positive 
predictive value (83%) (Freynhagen et al 2006). At study entry, subjects will complete the PDQ. 
Based on their scores, subjects will be separated into three groups: Group 1) subjects with NP in 
pregnancy (score ≥13); Group 2) subjects with non-neuropathic pain in pregnancy (1≥score≤12; 
and Group 3) subjects without any type of pain in pregnancy (score=0). 
 
Other measures collected at entry include a general biographical form (WMHP Intake Form). 
Subjects will complete pain measures and the Beck Depression Inventory (BDI) (Beck et al 1960) 
at study entry and at each study visit. Pain measures include the Visual Analogue Scale (VAS), 
Pain Catastrophizing Scale (PCS) (Sullivan et al 1995), and measures of pain intensity, pain 
interference, pain behavior - all three derived from Patient Reported Outcomes Measurement 
Information System (PROMIS) (Amtmann et al 2010; Revicki et al 2009; Cella et al 2010). At each 
visit, the exposure tracking form will record the timing (weeks of gestation) and dosage of all 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 7 of 19 
prescription and non-prescription medications used in pregnancy and the postpartum period. A 
urine drug screen will also be obtained at each visit testing for the presence or absence of the 
following: amphetamines/methamphetamines, barbiturates, benzodiazepines, THC, cocaine, 
methadone, opiates, PCP, and cotinine. For all visits following entry visit, subjects will complete 
the Patients’ Global Impression of Change scale (PGIC) (Hurst and Bolton 2004); and the clinician 
will complete the Clinical Global Impression-Global Improvement scale (CGI-I) (Guy 1976). At all 
study visits, weight and vital signs will be collected. For all subjects who delivered at UAMS, 
medical records for labor and delivery and neonatal outcome will be obtained following birth. All 
subjects will participate in Part A. All subjects will receive treatment as usual within each group. 
 
Part B: 
Subjects in group 1 will be invited to participate in part B of the study following their enrollment in 
part A. This pilot study will aim to enroll 10 subjects (of Group A). 
 
Subjects will undergo daily rTMS, defined as Monday through Friday, for a total of 10 consecutive 
sessions with the exception of weekends and holidays (i.e., Monday to Friday only). Typically, a 
stimulation period will start on Monday (day 1) and end on Friday (day 12). In the case that a 
stimulation period does not start on Monday, day 1 will begin on the day of the subject’s first rTMS 
session. Subjects will be followed daily until day 29, following their last session of rTMS (day 12). 
Table 2 provides an overview of study procedures. For each session (days 1-5 and 8-12), subjects 
will complete a VAS prior, immediately following, and 60 minutes post. Adverse events will also 
be recorded prior to and immediately following and 60 minutes after each session. They will 
complete a BDI on Days 1, 5, 12, 22, and 29. Subjects will complete VAS also on days 22 and 
29. For days 5, 12, 22, and 29; subjects will complete the PGIC; and clinicians will complete the 
CGI-I. Subjects will have a maximum of 12 visits for Part B (10 rTMS sessions plus days 22 and 
29). Either study visit for days 22 or 29 may occur in conjunction with a study visit for Part A. 
 
Repetitive transcranial magnetic stimulation will be applied using the NeuroStar TMS Therapy 
System with the XPLOR System in the PRI. For all subjects beyond 24 weeks gestation, they will 
be positioned on their left side using a wedge cushion to minimize the occurrence of inferior vena 
cava compression syndrome. Repetitive TMS will be applied through a figure-8 coil connected to 
a magnetic stimulator, which provides a biphasic pulse. The coil is applied to the primary motor 
cortex, M1, contralateral to the painful side. The optimal stimulus site, motor hot spot, will be 
determined according to visual detection of muscle twitches, and a resting motor threshold is 
defined as the minimal intensity necessary to induce at least one visible muscle twitch. At each 
rTMS treatment, study staff will determine resting motor threshold by stimulating the primary 
motor cortex (functional assessment of the primary motor cortex). To find the optimal stimulation 
site, study staff will measure the halfway distance between the nasion and inion and the halfway 
distance between the right tragus and left tragus. From the intersection of these two points, the 
optimal stimulation site is approximately 5cm lateral on the contralateral side. Study staff may 
need to adjust positioning to find the optimal site by moving in all angles by approximately 1 cm. 
To begin, study staff will set the TMS intensity to 35% stimulator output and deliver a single pulse 
over the optimal site with handle 45 degrees to the sagittal plane. Intensity will be increased 
progressively by 5% increments until a muscle evoked potential is seen as determined by relative 
visual inspection. Study staff will wait 6-10 seconds between stimuli to avoid cumulative effects. 
Once a muscle evoked potential is seen as determined by relative visual inspection, several 
stimuli will be delivered to ensure a consistent response. The stimulus intensity will then be 
lowered in 1% stimulator output until 50% positive responses are recorded (5 out of 10). This 
stimulus intensity plus 1% is then defined as the resting motor threshold. 
 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 8 of 19 
An rTMS session consists of 10 trains at 90% intensity of resting motor threshold. One train 
consists of 50 pulses at 5 Hz for a 10s duration. There is a 50s intertrain interval. A total of 500 
pulses are applied in a session for a cumulative exposure of 5000 pulses over 10 sessions. Each 
session lasts about one hour. 
 
All rTMS treatments will be administered by the PI (Dr. Ray-Griffith) or study staff who have been 
adequately trained to perform rTMS. Dr. Ray-Griffith will receive training for rTMS through the 
intensive course in TMS offered by the Berenson-Allen Center for Noninvasive Brain Stimulation 
at Beth Israel Deaconess Medical Center – a teaching facility of Harvard Medical Center and 
device specific training from the device manufacturer, Neuronetics, Inc. Device specific training 
from the device manufacturer, Neuronetics, Inc., will also be provided for study staff. If potential 
adverse events occur during the treatments, the PI will follow the data and safety monitoring plan, 
as stated below. All participants will receive prompt medical treatment. As treatments are 
completed in an outpatient setting, emergency services will be utilized in the event of a series 
adverse event prompting emergency medical treatment. 
 
Table 1: Data Information for All Study Participation (Part A) 
MEASURES 
ENTRY 
(≤24 weeks 
gestation) 
PREGNANCY VISITS 
(EVERY 4-6 WEEKS) 
POSTPARTUM VISITS 
(weeks postpartum) 
0-4 
5-8 
9-12 
SELF-REPORT MEASURES 
PDQ 
X 
 
 
 
 
General Biographical Form 
(WMHP Intake Form) 
X 
 
 
 
 
PCS 
X 
X 
X 
X 
X 
Pain Interference-Short Form 4A 
X 
X 
X 
X 
X 
Pain Behavior-Short Form 7A 
X 
X 
X 
X 
X 
Pain Intensity-Short Form 3A 
X 
X 
X 
X 
X 
VAS  
X 
X 
X 
X 
X 
BDI 
X 
X 
X 
X 
X 
PGIC 
 
X 
X 
X 
X 
CLINICIAN-RATED MEASURES 
CGI-I 
 
X 
X 
X 
X 
OTHER MEASURES 
Maternal Weight and Vital Signs 
X 
X 
X 
X 
X 
Exposure Tracking Form 
X 
X 
X 
X 
X 
OB/Delivery Records 
 
 
X 
 
 
Neonatal Records 
 
 
X 
 
 
Urine Drug Screen 
X 
X 
X 
X 
X 
 
Table 2: Data Information for rTMS Study Participation (Part B) 
MEASURE 
Days with rTMS 
Day 
1 
Day 
5 
Day 
12 
Day 
22 
Day 
29 
 
Pre  
Immediately 
Post 
60 mins 
Post 
VAS 
X 
X 
X 
 
 
 
X 
X 
Adverse Events 
 
X 
X 
 
 
 
 
 
BDI 
 
 
 
X 
X 
X 
X 
X 
PGIC 
 
 
 
 
X 
X 
X 
X 
CGI-I 
 
 
 
 
X 
X 
X 
X 
TASS 
X 
 
 
 
 
 
 
 
 
 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 9 of 19 
Initial Screening 
Subjects will be identified by clinical staff based on current pregnancy status to identify potential 
subjects for the study. Once referred, initial screening by research personnel will include reviewing 
inclusion and exclusion criteria (as described in Eligibility Criteria) discussing the study, obtaining 
informed consent, completing the TASS questionnaire and initiating enrollment. These 
assessments and health related information will be collected on a paper form. All personnel will 
be qualified to administer all questionnaires. 
 
Access to Medical Records: As a part of the informed consent for this protocol, individuals will 
allow the investigative team access to medical records. Any information acquired from medical 
records will be de-identified (no PHI, only subject ID code) and stored with the de-identified 
records obtained for this study. 
 
The medical record will be utilized to gather obstetrical information regarding gestation and 
delivery of the infant, which may include but not limited to infant weight, height, APGAR scores, 
gender, head circumference, method of delivery and maternal or infant complications. Collection 
of health information will occur shortly following delivery of infant. Infants will only be assessed 
via medical records. There will be no direct assessment of infants within the scope of this study. 
 
Questionnaires and Surveys for Parts A and B: 
• 
Pain Interference Scale-Short Form 4a (Part A): This 4-item self-report scale measures the 
consequences of pain on relevant aspects of the subject’s life. It includes impairment in the 
subject’s social, cognitive, emotional, physical, and recreational activities. It also incorporates 
items about sleep and enjoyment of life. The short form is not disease specific and assesses 
pain interference over the past 7 days. 
• 
Pain Behavior Scale-Short Form 7a (Part A): This 7-item, self-report scale measures 
behaviors that typically indicate to others that an individual is experiencing pain. These 
measures include observations (sighing, crying), behaviors (resting, guarding, facial 
expressions, asking for help), and verbal reports of pain. The short form is not disease specific 
and assesses pain interference over the past 7 days. 
• 
Pain Intensity Scale-Short Form 3a (Part A): This 3-item, self-report scale assesses how much 
a person hurts. The first 2 items assess pain intensity over the past 7 days and the last item 
asks the subject to rate their pain intensity “right now.” The short form is not disease specific. 
• 
Pain Catastrophizing Scale (PCS) (Part A): The PCS is a 13-item self-report scale. It asks 
subjects to reflect on past painful experiences, and to indicate the degree to which they 
experienced each of 13 thoughts or feelings when experiencing pain, on 5-point scales with 
the end points (0) not at all and (4) all the time. The PCS yields a total score and three 
subscale scores assessing rumination, magnification, and helplessness. 
• 
painDETECT Questionnaire (PDQ) (Part A): This self-report questionnaire consists of 7 
questions that address the quality of neuropathic pain syndromes. The first 5 questions ask 
about the gradation of pain, question 6 asks about the pain course pattern and question 7 
asks about radiating pain. There are 4 additional questions which asks the subject to rate their 
pain now and over the last 4 weeks and to mark on a body chart if there is pain radiating into 
other parts of the body. These last questions are not counted in the total score. 
• 
Exposure Tracking Form (Part A): This is a customized form used by study staff to document 
all exposures on a weekly basis during pregnancy and the postpartum period. 
• 
General Biographical Form (WMHP Pain Intake Form) (Part A): All subjects will complete a 
WMHP-Pain intake packet, which will be composed of several sections including: 1) general 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 10 of 19 
information or demographics; 2) gynecological history; 3) genetic history; 4) obstetrical history; 
5) current/most recent pregnancy; 6) surgical history; 7) drug and alcohol history; 8) family 
medical history; 9) medical history; and 10) current status. The intake form is used at baseline 
and may be updated as appropriate at follow up visits. 
• 
Beck Depression Inventory (BDI) (Part A and B): The BDI is a widely used instrument that has 
been used in both clinical and non-clinical setting measuring depressive symptoms. It is a 21 
item questionnaire with 4-5 responses for each question. Responses are coded 0-3 for the 4 
point scales. The 5 point scales include an additional 2a and 2b response code. The symptom 
categories reflect overt behavioral manifestations of depression. The instrument has both a 
high degree of reliability and validity (Beck, Ward, Mendelson, Mock & Erbaugh, 1961). This 
scale will be performed at every subject visit. 
• 
Patient’s Global Impression of Change Scale (PGIC) (Part A and B): The PGIC gives a global 
rating of change in symptoms, activities, emotion, and overall quality of life related to the 
subject’s pain condition. This is a self-rated scale. 
• 
Clinical Global Impression-Global Improvement Scale (CGI-I) (Part A and B): The CGI-I gives 
a global rating of the improvement/change in the symptoms since the last study visit. This is 
administered by the MD. 
• 
Visual Analog Scale (Part A and B): 100 mm line scale that is subject administered to 
subjectively rate current pain symptoms. The subject will be instructed to draw a single vertical 
line that best describes current state. The VAS will be administered at every subject visit. 
• 
TASS: TASS is the Transcranial magnetic stimulation Adult Safety Screen that is used to alert 
investigators to factors in potential subjects that may be predisposed to adverse events during 
rTMS. The decision to proceed with rTMS is entirely up to the investigator’s judgment. TASS 
compliments history-taking and is not meant to exclude or replace the investigator’s judgment. 
 
Maternal Labs 
We will obtain maternal urine collection for research analysis at every subject visit for urine drug 
screen and cotinine analysis. Urine will be collected and processed in a designated research 
space at PRI/UWC or in the subject’s room in PRI/UAMS and will be sent to an outside laboratory. 
WMHP research personnel process the research lab. All research samples will be temporarily 
stored in a dedicated -20 degrees freezers in the Psychiatric Research Institute (PRI) 4th floor 
laboratory. Access to the samples will be restricted to WMHP research personnel. 
 
Cotinine/Nicotine 
Many women may continue to use tobacco during pregnancy and may or may not inform their 
obstetrical care about such use. Given the well documented untoward effects on pregnancy 
outcome, each subject will be provided information about available smoking discontinuation 
programs in their geographic area and encouraged to discuss tobacco use with their obstetrical 
care provider. Obstetricians will not be informed of a positive cotinine/nicotine screen by the 
investigative team. 
 
Illicit Drugs 
Urine drug analysis is important in identifying exposure to substances; however, they are not done 
routinely during pregnancy. In reference to the current study, the urine drug screen is important 
to confirm exposure to prescription and non-prescription medications that may confound study 
results. Not surprising, some women taking medications choose not to inform their obstetrical 
care about such use or the extent of such use. These medications may include both prescription 
medications, medications obtained through other sources (e.g. internet), and illicit substances. 
We view this as highly problematic and not indicative of a collaborative clinical care plan to 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 11 of 19 
minimize obstetrical complications. Our experience has been that with effective education and 
supportive interactions, the majority of women will inform both their obstetrical and pediatric care 
providers. In the event that the subject refuses to notify their obstetrical care provider, this is 
viewed as a potential hazard to the pregnancy and infant, and in the opinion of the investigative 
team constitutes a ‘duty to warn’ – since the fetus cannot be warned, the subject will be asked to 
meet to discuss how to best inform their obstetrical care provider. The details regarding how to 
handle such medication use in pregnancy is not covered under the auspices of the social service 
offices in the Little Rock area. The subject’s obstetrical care provider will be notified by phone with 
the subject in the office to permit them to hear how the information is communicated. If the subject 
declines such a meeting, the obstetrical care provider will be notified. The study investigators are 
experienced with the treatment of substance abuse in pregnancy, and the study participants will 
be offered care for their substance abuse problem. Given the importance of providing these 
women optimal clinical care, we have found that having an office visit to discuss the results and 
treatment planning, as well as making contact with their obstetrical care provider in their presence 
has been remarkably successful at keeping the women engaged in care. 
 
Statistical Methods and Data Management 
All data will be kept either in locked file cabinets or password-protected computers accessible to 
only investigators or designated study staff. Trained study staff will enter data and original source 
documents will be stored in locked file cabinets in offices with limited access. A database will also 
be created to input subject information and only designated study staff will have access. Periodic 
reviews will occur to ensure that data is accurately entered and if needed, corrections can be 
made. The database will generate queries to account for missing information. Every subject 
enrolled in this study will be given a unique ID number that will be used for tracking purposes. 
The key linking the unique study ID number to identifiable information will also be stored in the 
password-protected computers accessible to only investigators or designated study staff. 
Each subject’s name, SSN, birth date, address, phone number, and email address will be 
obtained for purposes of payment and follow-up. We will ask for each subject’s drug use history, 
medical history, and current drug use. 
 
Part A: 
Descriptive statistics will be calculated for all measures obtained. 
 
For the first hypothesis, primary outcome measures include VAS and pain assessments. 
Secondary outcome measures include BDI, PGIC, and CGI-I. For each outcome measure, scatter 
plots will be constructed for visual inspection across time by group. As outcome measures will be 
obtained at multiple time points, mixed models will be used to account for the correlations among 
the measurements within the subjects. 
 
Table 3 provides a list of specific outcome data of interest for the second hypothesis. The 
occurrence of obstetrical outcomes will be compared between the three groups. If measures are 
normally distributed, we will use ANOVA to test the differences among the three groups. 
Otherwise, we will use a non-parametric method, such as Kruskal Wallis test, to test the difference 
among the groups. 
 
 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 12 of 19 
Table 3: Specific Outcome Data 
Obstetrical Records 
Neonatal Records 
• 
Preterm labor 
• 
Preterm birth 
• 
Premature rupture of membranes 
• 
Mode of delivery 
• 
1 minute and 5 minute APGAR Scores 
• 
Length of Hospitalization 
• 
Neonatal Intensive Care Unit Admission 
• 
Neonatal Abstinence Syndrome 
• 
Birth weight and length 
• 
Gender 
 
Part B (rTMS): 
We will determine the acceptability of rTMS as a treatment option by determining the percentage 
of subjects who accept the treatment when offered. Tolerability will be determined by the reporting 
of adverse events. The primary outcome measure is VAS. Secondary outcome measures include 
BDI, PGIC, and CGI-I. For each outcome measure, scatter plots will be constructed for visual 
inspection across treatment. Using previous studies of rTMS for the treatment of neuropathic pain, 
we will determine an effect size and complete a power analysis. This information will help guide 
future studies of the effectiveness of rTMS in the treatment of neuropathic pain in pregnancy. 
 
Neonatal outcomes will be analyzed between the following groups: 1. Subjects participating in 
rTMS (Part B); 2. Subjects with neuropathic pain who participated in Part A but did not participate 
in Part B; 3. Subjects with chronic non-neuropathic pain who participated in Part A; and 4. 
Subjects without chronic pain who participated in Part A. Specific endpoints of interest include 
neonatal intensive care unit admission, length of hospitalization, birth weight and length, and 1-
min and 5-min APGAR scores. The occurrence of obstetrical outcomes will be compared between 
the groups. If measures are normally distributed, we will use ANOVA to test the differences among 
the three groups. Otherwise, we will use a non-parametric method, such as Kruskal Wallis test, 
to test the difference among the groups. 
 
Neonatal outcomes will be scrutinized after each delivery and neonatal period. The investigator 
team will convene and review all neonatal outcomes to determine if any complication occurred 
that could be attributed to the study, participation in the study, and/or treatment received. If any 
complication is identified (i.e. preterm delivery with all subjects who participated in rTMS), we will 
cease all current and potential study procedures related to part B of the study. 
 
All statistical analysis will be completed using SAS 9.4. Significance will be set at p<0.05. 
 
Data Safety and Monitoring Plan 
A trained study staff member will perform the consenting in a quiet and private room. This person 
will review the consent with the subject and aid in the discussion. The consent discussion time 
will be determined based on the subjects’ questions and understanding of the consent form. 
Subjects will be informed of their rights and that by participating in this research will not impact 
their treatment now or in the future at UAMS. It will be emphasized that the research is voluntary. 
The person obtaining consent will carefully explain each element of the document and outline the 
risks and benefits, alternate treatment(s), and any follow-up requirements of the study. 
Participation privacy will be maintained and questions regarding participation will be answered. 
The language for the consent is in English and only those who comprehend English will be allowed 
to provide consent for this study. 
 
 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 13 of 19 
No coercion or undue influence will be used in the consent process. The steps that will be taken 
to minimize the possibility of coercion or undue influence include: 
1. Stressing that the study is of voluntary nature. 
2. Telling subjects they can leave the study anytime they choose. 
3. Assuring the subjects that there are no consequences to leaving the study and that 
acceptance or refusal to be in the study will not affect any treatment. 
 
We want to stress that the subject will be INFORMED of all the rights that go along with signing 
an informed consent to be in a voluntary study. The language used by those obtaining consent is 
English and the language understood by the prospective subject or the legally authorized 
representative will also be English. No research related procedures will be performed prior to 
obtaining informed consent. All signatures and dates will be obtained. A copy of the signed 
consent will be given to the subject. The informed consent process will be documented in each 
subjects’ research record. 
 
Data Handling and Recordkeeping 
The PI is responsible for monitoring data confidentiality and the safety of our subjects. Quality 
assurance will be monitored through a set of standard operating procedures that will be compiled 
and placed in binders. Our safety monitoring plan includes the following: 
1. The PI is the designated responsible entity; 
2. Immediately following stimulation, subjects will be inspected for signs of twitching and 
movement indicative of seizure by the study physician. 
3. In the event of seizure, the plan outlined under protection against risk will be followed by 
study personnel; 
4. The PI will report any adverse events to the IRB, Sponsor and funding agency as 
appropriate. 
 
Independent Study Monitoring 
The sponsor will conduct independent data safety and monitoring according to the ORRA 
Monitoring Plan. 
1. The Data and Safety Monitoring Plan describes operating procedures that will be in place 
to monitor compliance, study data validity and integrity, subject safety, individuals and/or 
entities (e.g., IRB) that will be involved in monitoring these procedures, and the 
frequency/regularity of this monitoring. 
2. For Part B, the PI will meet with the medical monitor after each 3 enrollments to review 
adverse events. 
3. UAMS IRB regulations will be strictly adhered to in the conduct of the proposed research. 
Specifically, prior to implementation of any protocol changes, amendments will be submitted 
to the IRB for approval. 
4. In terms of subject safety, if an adverse event occurs during the course of a study, guidelines 
in the UAMS IRB Investigator’s Handbook for adverse event and serious adverse event 
reporting will be followed. The PI will report all such activities to the IRB and the Sponsor. 
Additionally, the PI will inform the sponsor of any actions taken by the IRB resulting from its 
continuing review of this study. 
5. Monitoring of the aforementioned procedures will also be overseen by the PI, study 
coordinator, and the IRB. 
6. Data will be stored on a secure server only accessible to study staff members. Any breaches 
in the data integrity or confidentiality of subject information will immediately be reported to 
the PI and then, if necessary, to the IRB. All study staff will be trained in the protocol and 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 14 of 19 
study procedures. All staff on this study has completed Human Subjects and HIPAA training. 
Any deviations to the protocol will be reported to the PI and to the IRB. 
 
Termination of Study Participation: 
Patients will be informed that they have the right to withdraw from the study at any time for any 
reason, without prejudice to their medical care. The Principal Investigator also has the right to 
withdraw subjects from the study for any of the following reasons: 
• 
In the event of a seizure or other AE 
• 
Non-compliance 
• 
Protocol violation 
• 
Study terminated 
• 
At discretion of PI 
 
Risks and Benefits 
Identification of Adverse Events: 
An adverse event is defined as any new medical problem, or exacerbation of an existing problem, 
experienced by a subject while enrolled in the study, whether or not it is considered drug/device-
related by the investigator. 
 
Adverse Event Reporting 
All adverse events occurring during the course of the study, whether related to Part A or Part B 
or otherwise, will be recorded on the Adverse Event Case Report Form. For all adverse events, 
the Investigator will provide an assessment of the adverse event, its treatment and resolution, 
and its relationship to the study. Special reporting procedures are required for certain adverse 
events. 
 
Relationship of Adverse Events to the Investigational Device 
The investigator will assess the relationship of the adverse event to the investigational device. 
The relationship will be assessed using the following categories: 
• 
Definitely Related: A direct cause and effect relationship between the investigational drug 
or device/experimental treatment and the adverse event exists. 
• 
Possibly Related: A direct cause and effect relationship between the investigational drug or 
device/experimental treatment and the adverse event has not been clearly demonstrated, 
but is likely or very likely. 
• 
Unlikely Related: A direct cause and effect relationship between the investigational drug or 
device/experimental treatment and the adverse event is improbable, but not impossible. 
• 
Unrelated: The adverse event is definitely not associated with the investigational drug or 
device/experimental treatment. 
 
Unanticipated Adverse Device Effects  
An unanticipated adverse device effect is defined as “any serious adverse effect on health or 
safety, or any life-threatening problem, or death caused by, or associated with, a device; if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence 
in the investigational plan, or application (including supplementary application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare 
of subjects.” If an unanticipated adverse effect occurs, the investigator will promptly notify the 
sponsor of such an event within 24 hours of first learning of the event using the FDA MedWatch 
3500A form. The form can be found online at: https://www.fda.gov/media/69876/download. 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 15 of 19 
Serious Adverse Events 
Each adverse event will be assessed for its seriousness using the criteria outlined below. The 
term serious adverse event is not synonymous with a “severe” adverse event, which may be used 
to describe the intensity of an event experienced by the subject. An adverse event will be 
classified as serious if it meets any of the following criteria: 
• 
Results in, or contributes to, a death 
• 
Life-threatening (i.e., the subject was, in the opinion of the investigator, at risk of death at 
the time of the event, but it does not include an event that, had it occurred in a more severe 
form, might have caused death) 
• 
Results in a substantial disruption of a person's ability to conduct normal life functions, i.e., 
the adverse event resulted in a significant, persistent or permanent change, impairment, 
damage or disruption in the patient's body function/structure, physical activities and/or 
quality of life. 
• 
Results in permanent disability or incapacity (i.e., permanent impairment of a body function 
or permanent damage to a body structure) 
• 
Requires in-subject hospitalization or prolongs hospitalization 
• 
Necessitates medical or surgical intervention to preclude a permanent disability or 
incapacity 
• 
Results in a congenital anomaly or birth defect 
 
Non-serious adverse events are all events that do not meet criteria for a “serious” adverse event. 
 
If serious adverse event occurs, the investigator will promptly notify the sponsor of such an event 
within 24 hours of first learning of the event using the FDA MedWatch 3500A form. The can be 
found on-line at: https://www.fda.gov/media/69876/download 
 
The investigator will also promptly notify the IRB of such an event as soon as possible, but no 
later than ten (10) working days after first learning of the event. 
 
Severity 
Each adverse event will be assessed for its severity, or the intensity of an event experienced by 
the subject, using the following. 
• 
Mild: Discomfort noticed, but no disruption to daily activity. 
• 
Moderate: Discomfort sufficient to reduce or affect normal daily activity. 
• 
Severe: Inability to work or perform normal daily activity. 
 
Deaths 
The investigator will notify the sponsor and IRB as soon as possible, preferably within 24 hours 
but in no event later than 48 hours, of learning of subject’s death, regardless of whether the death 
is related or unrelated to the investigational drug or device. The investigator will attempt to 
determine, as conclusively as possible, whether the death is related to the drug or device. The 
cause of death and the investigator’s discussion regarding whether or not the death was drug- or 
device-related will be described in a written report. 
 
Pre-existing conditions 
Pre-existing conditions will not be reported as an adverse event unless there has been a 
substantial increase in the severity or frequency of the problem, which has not been attributed to 
natural history. 
 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 16 of 19 
Eliciting and Reporting Adverse Events 
The investigator will assess subjects for the occurrence of adverse events at each study visit. All 
adverse events (serious and non-serious) reported by the subject will be recorded on the source 
documents and CRFs. 
 
Abuse of illicit or licit substances during pregnancy poses a potential risk to the subject and their 
pregnancy that their obstetrical and pediatric care provider should be aware. As a policy, we 
strongly encourage subjects to communicate this information to their obstetrical and pediatric care 
providers. We will only share this information with other care providers with subject’s signed 
release of information. To the best of our knowledge, participation in part A of this study poses no 
risk to pregnancy and/or the infant. There may be risks, discomforts, or side effects that are not 
known yet. There is also the possibility of loss of confidentiality. 
 
Risks Associated with Part A 
No real risks are associated with Part A of this study other than possible loss of confidentiality. 
Subjects may decline to answer any questions that may make subjects uncomfortable. 
 
Risks Associated with rTMS (Part B) 
Likely: Subjects may feel anxious about participation. This typically abates after the first one or 
two sessions. 
 
Less likely: Subjects may experience minor discomfort associated with head and hand muscle 
twitching, headache, local (head and neck), and dental pain. Head and neck pain related to 
stimulation of underlying muscle and nerves occurs in approximately 10% of subjects. The 
incidence and severity is a function of stimulus site and intensity but is most common over frontal-
temporal regions. The symptoms are typically mild and limited to the time of stimulation and can 
be treated with acetaminophen if necessary. Subjects typically tolerate the discomfort better as 
session’s progress. The coil position is adjusted if pain occurs. Subjects will be advised to take 
acetaminophen for treatment if necessary. The study physician or nurse will monitor subjects 
during and after each rTMS for twitching of a hand muscle, such as the abductor pollicis brevis or 
the first dorsal interosseous muscle, on the side of the body that is contralateral to the rTMS 
treatment site. 
 
Rare: Seizure and hearing loss. The risk of having a single seizure is small, estimated at 
≤1/10,000 (Rossi et al 2009). In order to decrease this risk, subjects with preeclampsia, brain 
lesions, head trauma, a history of seizures (e.g., epilepsy), or taking medications known to lower 
seizure threshold are precluded from participating in rTMS. Study staff administering rTMS are 
trained in the treatment and management of an acute seizure. Life-support equipment is also 
readily available. All subjects will be visually monitored for signs of a seizure and/or muscle 
twitching throughout each rTMS treatment. 
 
Another risk is hearing loss (temporary or permanent). To minimize this risk, subjects will wear 
ear plugs during rTMS. Subjects will be asked to immediately report any loosening or detachment 
of an earplug during treatment. Study staff will immediately stop rTMS if a subject reports or if an 
investigator observes that a subjects’ ear plug has loosened or has fallen out. 
 
Rare: A specific, but rare, risk of rTMS in pregnancy is inferior vena cava syndrome (or supine 
hypotensive syndrome). This syndrome happens in pregnancy after 24 weeks pregnant and 
usually occurs after laying down for about 5-10 minutes. Common symptoms are feeling dizzy 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 17 of 19 
and/or upset to your stomach and having low blood pressure and/or high heart rate. The 
symptoms do not last long and usually go away when you change your position, such as lay on 
your left side. To decrease the chance of this happening, you will have a cushion placed under 
you right side during treatments when you are 24 weeks pregnant or greater. 
 
Temporary changes in vision may be noticed immediately after rTMS. These visual changes are 
not thought to be actual problems with the eyes, but, rather changes in brain functioning as a 
result of rTMS. Things like blurred vision and/or eye floaters normalize in time. The risk will be 
minimized by using conservative stimulation parameters. 
 
Facial numbness and facial nerve stimulation may also occur. Some sources estimate that 1 out 
of 3 individuals experience “facial twitching” during and/or after rTMS sessions. This twitching in 
the facial muscles is caused by intense electrical stimulation that penetrates the cortex. We will 
minimize this risk by using as conservative stimulation parameters as possible to meet the goals 
of the study. 
 
Some patients may have fainted (syncopal/convulsive syncopal) or become lightheaded and 
nauseous during rTMS. We would stop TMS in case of suspected syncope. Such symptoms have 
been brief and resolved completely. In order to minimize risks the study doctor or nurse will use 
the following procedures to minimize the risks of convulsive syncope: 
• 
Request information regarding a history of syncope during your screening process 
• 
Monitor blood pressure during rTMS 
• 
Monitor you for signs and symptoms of syncope appearing during rTMS and stop 
stimulation if signs and/or symptoms occur 
• 
Immediately place you in a reclining position elevating your legs if signs or symptoms of 
syncope appear 
 
Temporary changes in mood, such as mania and hypomania, have been caused by rTMS with 
high frequency stimulation. There are no reports of lasting changes in mood using the rate of 
stimulation that will be used in this study. To minimize this risk, subjects with a history of bipolar 
disorder have been excluded from participation in the study. In addition, subjects will be assessed 
clinically by the PI daily after each rTMS session for the development of mania or hypomania. If 
they develop during the study, the subject will be withdrawn from the study and referred for 
appropriate treatment as indicated. The PI is trained in the assessment and treatment of 
hypomania and mania. 
 
Ferromagnetic pigments may interfere with rTMS treatments, and some forms of eye make-up, 
especially eyeliner, eye shadow and mascara, may contain ferromagnetic pigments. To minimize 
this occurrence, all subjects will be asked to remove all forms of eye makeup before each rTMS 
treatment. 
 
The long-term effects of rTMS are unknown. 
 
There may be benefit to subjects in this study who are participating in rTMS. For all others, taking 
part in this research study may not benefit the subjects personally, but we may learn new things 
that may be of benefit to women and children in the future. 
 

Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 18 of 19 
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Protocol Title: Neuropathic Pain in Pregnancy 
Institution: University of Arkansas for Medical Sciences (UAMS) 
IRB Number: 204737 
Sponsor: UAMS 
PI: Shona L. Ray-Griffith, MD 
Version 10, 03.30.2021 
Page 19 of 19 
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