The Ability of Brain Waves Activity to Detect Patient Susceptibility to Post-Operative Pain
Conditions: Pulp Disease, Dental
Sponsor: Ain Shams University

STUDY PROTOCOL – COVER PAGE 
 
 
 
Official Title: 
The Ability of Brain Waves 
Activity to Detect Patient 
Susceptibility to Post- 
Operative Pain 
ClinicalTrials.gov Identifier 
(NCT): 
Not yet assigned 
Institution: 
Faculty of Dentistry, Ain 
Shams University 
Principal Investigator: 
Ahmed Reda Abd El 
Rahman Hammad 
Supervisors: 
Dr. Ahmed Abd El Rahman 
Hashem (Professor and 
Chairman of the 
Endodontic Department) 
Dr. Mohamed Mokhtar 
Nagy (Professor of 
Endodontics) 
Dr. Mohamed Mohamed 
Elashiry (Lecturer of 
Endodontics) 
Ethics Approval Serial No.: 
FDASU-Rec IM122127 
Document Version: 
v2.0 
Document Date: 
22-Dec-2021 

The Ability of Brain Waves Activity to Detect 
Patient Susceptibility to Post-Operative Pain 
 
Research proposal submitted to Department of Endodontics, Faculty of 
Dentistry, Ain Shams University, in partial fulfilment of the requirements 
of the Master’s Degree in Endodontics. 
Submitted by 
Ahmed Reda Abd El Rahman Hammad 
(B.D.S, Ain Shams University, 2018) 
 
Supervised by 
Dr. Ahmed Abd El Rahman Hashem 
Professor and Chairman of the Endodontic Department 
Faculty of Dentistry 
Ain Shams University 
 
Dr. Mohamed Mokhtar Nagy 
Professor of Endodontics 
Faculty of Dentistry 
Ain Shams University 
Dr. Mohamed Mohamed Elashiry 
Lecturer of Endodontics 
Faculty of Dentistry 
Ain Shams University 
2021 

Introduction 
Pain is an unpleasant sensory and emotional experience associated with 
actual or potential tissue damage. It is the primary reason for patients to seek 
dental therapy and mostly this pain is related to endodontics. 
Pain and fear of pain is at the root of many problems between patient and 
dentist. Endodontic treatment, because of its strong association with 
preoperative, operative and postoperative pain, is prominent in this regard. Pain 
prevention is, thus, of prime importance in endodontics. 
Root canal treatment is usually associated with pain before, during or even 
after the treatment done. Dentists, especially endodontists, have the ability to deal 
primarily with pain intraoperatively by local anesthesia but sometimes it is 
difficult to control post-operative pain or even expect its degree as it is related to 
many factors. Knowledge of the causes and mechanisms behind endodontic 
postoperative pain is necessary for the clinician to properly manage this 
undesirable condition. 
Pain measurement is usually subjective; it is not always possible to 
quantify pain. Mostly the physicians rely on tools to measure pain as the visual 
analogue scale (VAS) for assessment of the patient’s pain intensity. Although it 
has many pros, it is still highly subjective. 
According to a recent study, brain rhythms can be used to predict how 
sensitive individuals are to pain. An electroencephalogram (EEG) is used to 
measure brain activity by placing electrodes on the brain or outer skull surface. 
This study claimed that measuring the frequency of alpha waves in the resting 
state can predict patient sensitivity to pain. Alpha waves occur in healthy awake 
adults while resting with their eyes closed. They vanish during sleep and become 

replaced by beta waves when a person concentrates on a specific task. Alpha 
wave rhythms can range in frequency from 8 to 14 Hz. Alpha waves are maximal 
in the occipital region. In most cases, a neurologist will measure the alpha rhythm 
in the back of the patient's head while the patient's eyes are closed. [1] 
An electroencephalogram (EEG) is a printed record of the electrical 
activity of the brain. The billions of brain neurons and their activities generate a 
measurable electrical field that changes constantly when areas are stimulated or 
reduced in activity. The observed electrical patterns are referred to as brain 
waves. Brain waves are any number of patterns of rhythmic electric impulses 
produced in various parts of the brain. There are four types of brain waves: alpha, 
beta, theta, and delta. 
This interesting study that stated that the patient’s susceptibility to 
postoperative pain can be detected according to alpha brain waves activity is of a 
huge benefits and interest. The ability to predict the group of patients who are 
more likely to experience higher post-operative pain intensity than other patients 
will allow the implementation of the proper pain management protocols 
especially for this group of the patients, and that’s why this study will be 
conducted. 

Literature review 
Pain is a signal in your nervous system that something may be wrong. It is 
an unpleasant feeling. Pain may be sharp or dull. It may come and go, or it may 
be constant. 
Postoperative pain is defined as pain of any degree that occurs after the 
initiation of root canal treatment while flare up is a severe pain or swelling after 
initiation or continuation of endo treatment that require an emergency visit for 
the patient. [2] 
The incidence and degree of post endodontic pain occurring in 
asymptomatic patients who started endodontic treatment were recorded. It was 
found that postoperative pain is most likely to occur during the first 24 hours after 
obturation. If a patient is free of symptoms 24 h after obturation, it is unlikely 
that symptoms will develop during the 60 days after obturation. Postoperative 
pain has no statistically significant relationship with the vitality status of the pulp, 
the presence or absence of a periapical radiolucent area, the number of roots, 
previous emergency treatment for pain, or the level of obturation of the root canal. 
It was also found that patients who felt pain intraoperatively or between visits are 
more likely to develop postoperative pain. [3] 
Mild discomfort following root canal treatment is a common occurrence 
for patients. However, there can be numerous causes of postoperative pain. The 
most common causes are mechanical, chemical, or microbial injuries to the 
periapical tissues, which result in acute inflammation. In a clinical study, it is 
difficult to determine whether a single or multiple factors cause pain. If a root 
canal system was not properly cleaned, residual infection may cause exacerbation 
through imbalances in the host-bacteria relationship, synergistic or additive 

microbial interactions, or the presence of decisively pathogenic bacteria prior to 
treatment initiation. Over instrumentation may be a mechanical cause, while 
chemical causes include the extrusion of medications, filling materials, or 
irritants. [4] 
A study compared the effect of a one-visit root canal treatment (RCT) 
versus a two-visit RCT on post-obturation pain experience in single-rooted teeth 
with vital pulps. The findings were consistent with the majority of published 
reports that post-obturation pain in teeth with vital pulps following one-visit RCT 
was comparable to pain experienced following two-visit treatment. As a result, 
the prevalence or intensity of post-obturation pain was not significantly different 
between the one-visit and two-visit RCTs. [5] 
Occlusal reduction can prevent postoperative pain if the tooth was vital, 
sensitive to percussion or without periapical radiolucency. That is because 
occlusal reduction reduces occlusal stresses from periodontal ligament. [6] 
It seems that women are at a greater risk for many clinical pain conditions. 
An extensive review reported that a survey of the currently available 
epidemiological and laboratory data indicates that there is strong evidence for 
clinical and experimental sex differences in pain. Numerous reasons for these 
findings have been given, including hormonal and genetically driven sex 
differences in brain neurochemistry. [7] 
There is link between a patient's level of anxiety and how they react to an 
endodontic procedure. Many patients are dentophobic and don’t usually visit 
their dentist unless they feel severe pain lading to deterioration of their oral health 
condition. As the level of anxiety increases, the patient's pain threshold decreases. 
An implant study determined that pain experienced by patients was best predicted 

by their anxiety level during each procedure; these results could be correlated to 
endodontics. [8]. 
As endodontic treatment is always associated with pain, analgesics are 
always prescribed to avoid or decrease the postoperative pain. A respectful 
clinical study with a double-blind design compared the analgesic effect of 
different analgesic combinations and concluded that one or two tablets of the 
single-tablet combination of ibuprofen/paracetamol were statistically significant 
in reducing postoperative pain than two tablets of paracetamol/codeine and 
significantly superior pain relief compared to ibuprofen/codeine. [9] 
A systematic review and meta-analysis provided that there is no 
statistically significant difference in the risk of complications between single and 
multiple visit root canal treatment, however there is increased risk of flare-ups in 
case of single-visit root canal treatment in certain cases like those with periapical 
lesions. [10] 
A Visual Analogue Scale (VAS) is a subjective measurement instrument 
that tries to measure the intensity of pain and to follow up pain progression or 
regression. It is a line with "least possible pain" labelled at one end and "worst 
possible pain" at the other. The patient is asked to mark the line at a point 
corresponding to his present pain level. [11] 
Even though pain is a subjective first-person experience, and self-report is 
considered the gold standard for evaluating pain intensity in clinical situations, 
self-reports of pain intensity are not available in some vulnerable populations, 
which may result in inadequate or suboptimal pain treatment. An objective 
measurement of pain intensity that can supplement self-reports, for example, to 
monitor the effect of analgesic drugs or the recovery of the nociceptive system in 
non-communicative patients, is in high demand in clinical practice. [12] 

Pain vision PS-2100 (PV) is an objective analytical instrument that was 
designed to quantitatively and objectively assess sense perception and 
nociception in patients. A study compared PV to VAS to assess pain perception 
in the same patients and found that a weak correlation observed between VAS 
and PV. [13] 
Tissue injury, inflammatory illness, pathogen invasion, and neuropathy all 
contribute to pain, one of the most unpleasant feelings. The pain signal is 
transmitted to the brain via the spinal cord by nociceptors on the A- and C-fibers 
that innervate the skin, joints, and bodily organs, and is interpreted as pain. 
Neuronal activity in the brain is thought to play a role in pain perception. The 
dynamics of the neural activity that underpins pain perception, however, are not 
completely understood. [14] 
A study aimed to create a new method for predicting pain perception from 
single-trial laser-evoked potentials that was practical (LEPs). To automatically 
and accurately estimate single-trial LEP features, they used a unique single-trial 
analytic method that incorporated common spatial pattern and multiple linear 
regression. They also used a Nave Bayes classifier to predict low and high pain 
discretely, as well as a multiple linear prediction model to predict pain intensity 
continuously from single-trial LEP characteristics, at both within- and cross- 
individual levels. The proposed approach provided a binary prediction of pain 
(classification of low pain and high pain) with an accuracy of 86.3 8.4% (within- 
individual) and 80.3 8.5 percent (cross-individual), as well as a continuous 
prediction of pain (regression on a continuous scale from 0 to 10) with a mean 
absolute error of 1.031 0.136 (within-individual) and 1.821 0.202 (cross- 
individual) (cross-individual). As a result, the proposed method could aid in the 

development of a quick and accurate tool for pain prediction that could be used 
in a variety of basic and clinical settings. [15] 
Quantitative EEG is an objective noninvasive tool for studying the 
mechanisms involved in chronic pain. Increased alpha and theta power at 
spontaneous EEG and low amplitudes of ERP (event-related potentials) during 
various stimuli seem to be clinical characteristics of individuals with chronic 
pain. However, more studies are necessary before drawing any conclusion on the 
utility of qEEG on chronic pain. [16] 
A recent study looked at the relationship between healthy people's pain- 
free resting alpha oscillation speed and their sensitivity to two types of prolonged 
pain, Phasic Heat Pain and Capsaicin Heat Pain, over the course of two visits 
separated by an average of eight weeks (n = 61 Visit 1, n = 46 Visit 2). The speed 
of a person's pain-free alpha oscillations was shown to be negatively correlated 
with sensitivity to both models, and this association was found to be consistent 
across short (minutes) and long (weeks) timescales. Furthermore, the speed of 
pain-free alpha oscillations can be used to accurately identify people who are 
particularly sensitive to pain. These findings imply that alpha oscillation speed is 
a viable biomarker of long-term pain sensitivity that might be used to predict pain 
sensitivity in clinics [1] 
Alpha wave is the main brain wave of normal relaxed adults. It’s also about 
relaxation and freedom. When it is high (10-12hz), it is related to the active 
activity of the brain and when the energy released by the alpha wave is strong, it 
represents the brain wave in the best state of learning and thinking. [17] 
Tissue injury, inflammatory illness, pathogen invasion, and neuropathy are 
all causes of pain. The brain's neuronal activity is thought to play a role in pain 
perception. The patterns of neural activity that underpin pain perception, 

however, are unknown. A recent study examined theta oscillation patterns of 
local field potentials in the primary somatosensory cortex of a mouse model of 
formalin-induced pain. Formalin injection caused a reversible shift in theta-peak 
frequency toward a slower frequency. This shift was found during nociceptive 
phases but not during the pain-free interval, and it was inversely related to the 
degree of immediate pain. Furthermore, instantaneous oscillatory analysis 
revealed that during nociceptive phases, the likelihood of slow theta oscillations 
increased, accompanied by increasing slow theta power. Finally, cross frequency 
coupling between theta and gamma oscillations revealed that theta oscillations' 
coupling peak frequency was pushed toward slower oscillations, with no effect 
on coupling strength or gamma power. These findings imply that theta 
oscillations in the mouse primary somatosensory cortex reflect the continuing 
condition of pain sensation. [18] 
The cortical representation of relevant sensory information has been linked 
to 
neuronal 
oscillations 
in 
the 
gamma 
frequency 
band. 
Using 
magnetoencephalography, 
selective 
nociceptive 
stimuli 
induce 
gamma 
oscillations between 60 and 95 Hz in the primary somatosensory cortex. The 
amplitudes of pain-induced gamma oscillations vary with the objective stimulus 
intensity and the subjective pain intensity. However, around the pain threshold, 
perceived stimuli produced stronger gamma oscillations than unperceived stimuli 
of equal stimulus intensity. So painful stimuli cause high-frequency oscillations 
in the electrical activity of the human primary somatosensory cortex. The 
amplitudes of these pain-induced gamma oscillations were more closely related 
to the subjective perception of pain than to the objective stimulus attributes. 
These findings suggest that gamma oscillations may be an important mechanism 
for processing behaviorally relevant sensory information. [19] 

Aim of this study 
The aim of this study is to investigate the correlation between brain waves 
and prediction of postoperative pain in endodontic patients. 
 
 
 
 
 
 
 
 
Null Hypothesis 
There is no difference in post endodontic pain susceptibility between 
patients with different frequency of alpha brain waves. 

Materials and methods 
Materials 
EMOTIV®| EPOC X (EPOC X, Emotiv Inc, San Francisco, California, 
U.S.A) 
 
 
Methods 
 Setting and location 
After the approval of the ethics committee in Faculty of dentistry, Ain 
Shams University, patients who are regularly visiting the endodontic 
clinic on daily basis will be asked to participate in the study. The patients 
will be asked to wear an EEG device to record the alpha brain waves 
before and after receiving the required endodontic treatment. 
 
 
 Sample size determination 
A power analysis is designed to have adequate power to apply a 2-sided 
statistical test of the research hypothesis (null hypothesis) that there will 
be no difference in post endodontic pain susceptibility between patients 
with different frequency of alpha brain waves. The predicted sample size 
(n) is a total of (100) cases i.e. (50) cases per group. 
 
 
 Ethical consideration 
Patients will be asked to follow general instructions to sign a printed 
consent explaining the aim of the study and obligating them to fill the 

VAS scale during the procedure. Any patient who refused to participate 
in the study will have his endodontic needs fulfilled without any prejudice. 
 
 
 Patient selection 
The individual diagnosis will be confirmed by obtaining a dental history, 
performing pulp vitality testing, taking periradicular radiographs, 
periodontal evaluation, percussion, and a record of previous NSAID or 
antibiotic treatment. 
 
 
Inclusion criteria: 
1. Patient’s age ranges from 20-40. 
2. Vital lower first molar with signs and symptoms of acute irreversible 
pulpitis and indicated for single visit root canal treatment. 
3. Patients that had not received any medicinal therapy after 
endodontic treatment. 
4. Patients who are mentally and physically capable to record pain 
intensity estimated every 6 hours after endodontic treatment using 
VAS. 
 
 
Exclusion criteria: 
1. Patient systemic disease or neurogenic disease that contraindicates 
the use of the EEG or have sensitivity to the electrode material. 

2. Cases that root canal treatment could not be finished in a single visit 
such as teeth with apical periodontitis, pulpal necrosis, chronic 
apical abscess. 
3. Patients who took analgesics within 24 hours after endodontic 
treatment. 
 
 
Procedure steps: 
- All teeth will be cleaned, shaped, and obturated during the patients’ first 
visit. Local anesthesia will be achieved by inferior alveolar nerve block 
with 4% articaine with 1:100,000 epinephrine. After anesthesia, an 
endodontic access cavity will be done using suitable round bur and fine 
tapered stone with rounded end. 
- Canals will be prepared using crown down technique using manual and 
rotary instruments. Patency will be established and verified with #10 k 
files. 
- The ideal working length will be determined using an electronic apex 
locator and periapical radiographs 
- Glide path will be maintained with stainless steel hand instruments up 
to size #15. Shaping with rotary files 20 .04 and 25 .06 then final apical 
preparation by manual flex files. 
- The final instrumentation size will be determined as three sizes larger 
than the first file engaging at the working length. Master apical files 
ranging from #35 to #50, depending on both root anatomy and initial 
diameter of the root canal. 
- Irrigation performed with 5.25% NaOCl solution. 

- Teeth will be obturated with cold lateral compaction, using resin sealer 
and gutta-percha. 
 
 
 Sample classification 
This is an observational study. Alpha brain waves activity will be measured 
for all patients before root canal treatment and patients will be divided into 
2 groups: 
Group I: patients with low alpha frequency preoperatively ranging 
from 8 to 10. 
Group II: patients with high alpha frequency ranging from 11 to 13. 
The alpha brain waves activity will be recorded immediately after the 
endodontic treatment and 24 h post-treatment. The pain intensity will be 
recorded by the patient post-operatively every 6h using the VAS. 
 
 
 Method of evaluation 
The data from the EEG and the VAS records pre-and post-treatment will 
be evaluated, tabulated, correlated and statistically analyzed using the 
appropriate statistical test. 

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