Effects of Photobiomodulation on Postoperative Pain After Primary Endodontic Therapy in Molars With Symptomatic Apical Periodontitis
Phase: NA
Conditions: Postoperative Pain
Sponsor: The University of Texas Health Science Center, Houston

IRB NUMBER: HSC-DB-21-0579 
IRB APPROVAL DATE: 09/14/2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
Effects of Photobiomodulation on Postoperative Pain After Primary Endodontic 
Therapy in Molars With Symptomatic Apical Periodontitis 
 
NCT05032612 
 
Version Date: 9/14/2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

IRB NUMBER: HSC-DB-21-0579 
IRB APPROVAL DATE: 09/14/2021 
 
 Protocol Title: Effects of photobiomodulation on postoperative pain after primary endodontic 
therapy in mandibular molars with symptomatic apical periodontitis 
 
Principal Investigator: 
Dr. Ryne Jackson 
 
Co-Investigators: 
Dr. Juliana Barros, Dr. Renato Silva, Dr. Timothy Kirkpatrick, Dr. 
Shalizeh Patel. 
 
Population: Sample size = 52 adult patients ages 18 and older divided into two groups 
(intervention group and control group) 
 
Number of Sites: 1 site; UT School of Dentistry Graduate Endodontic Clinic 
 
Study Duration: One year - Two academic semesters 
 
Subject Duration: One dental visit - approximately 2 hours 
 
 
General Information 
 
Teeth diagnosed with SAP are more prone to present postoperative pain even after root canal 
therapy (RCT) is completed. Photobiomodulation (PBM) has been used for decades in medicine 
and dentistry showing promise results in the healing capabilities, however, an accepted protocol 
has still not been created for its regular use in endodontics. PBM utilizes the body’s own 
hardware by working specifically on the mitochondria in cells to improve patient healing and 
reduce post-treatment pain. The mitochondrial events taking place during PBM are thought to be: 
increased ATP production, release of nitric oxide, and release of reactive oxygen species. All of 
these events lead to an increase in cellular mediators involved in inflammation and pain control 
and thus PBM can greatly improve the outcomes of our endodontic treatment on these teeth. 
 
The aim of this clinical study is to investigate the use of PBM after primary root canal therapy in 
mandibular molars diagnosed with symptomatic apical periodontitis (SAP) to reduce 
postoperative pain. 
 
Fifty-twodult patients will be invited to participate in this study. They will be divided in 2 
groups: Control group where patients will receive conventional RCT (n=26) and PBM group 
where patients will receive conventional RCT plus PBM immediately post-operatively (n=26). 
Pre-operative and postoperative pain will be accessed by using a visual analogue pain scale. Data 
will be analyzed using continuous ordinal regression and distribution-free methods (Wilcoxon, 
Mann-Whitney tests) 
 
Background Information 
 
One of the main goals of endodontic (root canal) therapy is to eliminate pain. It has been well 
described in the literature that certain teeth tend to hurt more after root canal therapy. 
Preoperative pain intensity, pain interfering with daily activities, pain made worse with stress, 

IRB NUMBER: HSC-DB-21-0579 
IRB APPROVAL DATE: 09/14/2021 
 
and diagnosis of symptomatic apical periodontitis were all listed as independent predictors of 
severe pain intensity following root canal therapy (Law et al, 2015). Another study looked at 
similar predictors of postoperative pain and found mandibular molars to have significantly more 
postoperative pain than maxillary molars (Sadaf, 2014). 
 
Our everyday options for post-treatment pain is mostly limited to various prescription 
medications. This should be considered a major limitation especially in today’s world where we 
are fighting an active opioid crisis. 
 
According to the CDC, from 1999-2019 nearly 841,000 people died from an overdose involving 
prescription and illicit opioids. Nearly 247,000 Americans lost their lives to overdoses involving 
prescription opioids in the same two-decade time period. The good news is that the trend is now 
declining and doctors are prescribing opioids with much more caution. From 2006-2017 there 
was a 19% reduction in annual prescribing of opioids but the amount of opioids in morphine 
milligram equivalents (MME) prescribed per person is still around 3x what it was in 1999. 
 
Today, we know through an overwhelming amount of evidence that NSAIDS, Acetaminophen, 
and long-acting local anesthetics may result in greater analgesia for our patients than opioids. 
Acetaminophen and NSAIDS are great in dealing with pain, however their effectiveness is rather 
limited. Both Acetaminophen and NSAIDS are subject to a ceiling dosage with regard to 
effective analgesia. This means that past a certain dosage, the patient cannot achieve any greater 
pain relief than what was provided before they reached that ceiling dose. The point is – there are 
dozens of unique situations where practitioners need to have more tools available in dealing with 
pain when the standard protocol is ineffective. 
 
One such way of dealing with this pain is using Photobiomodulation (PBM), also known as low- 
level light therapy (LLLT), to deal with post-treatment pain. Photobiomodulation’s effects on 
accelerating the healing process were introduced in the 1960s but its use in dentistry is still not 
all that commonplace. The generally accepted mechanism of action is that absorbed light from 
the laser on the target tissue creates reactive oxygen species which leads to gene transcription 
and cellular healing. Mitochondria are very receptive to this process and the near-infrared light is 
absorbed and the energy is converted into ATP for cellular functions. Cytochrome C is key to 
this process as it is a chromophore and accepts the light to move these processes forward—at 
least that is the current level of thinking on the subject. There have been many studies showing 
the effects of PBM on healing in various medical specialties including dentistry but an accepted 
protocol has not yet been standardized. The Grotthus-Draper law or law of photochemical 
activation states that only light which is absorbed by a system can bring about a photochemical 
change. The correct wavelength for the target cells chromophores to induce the desired effect of 
PBM is 633 – 830 nm according to Kim and Calderhead. In this study, we will be using 660 nm 
to achieve our desired and expected results with PBM. 
 
Objective: 
The aim of this study is to evaluate the effects of photobiomodulation (PBM) on postoperative 
pain after endodontic treatment in mandibular molar teeth diagnosed with symptomatic apical 
periodontitis. 

IRB NUMBER: HSC-DB-21-0579 
IRB APPROVAL DATE: 09/14/2021 
 
 
Study Design: 
 
This randomized clinical trial is designed to evaluate the effects of photobiomodulation (PBM) 
on patients with symptomatic apical periodontitis (SAP) receiving root canal therapy. 
Fifty-two patients (n=52) diagnosed with SAP will be selected and invited to participate in the 
study. 
 
The inclusion criteria: 
• 
Patients over 18 years old 
• 
Posterior mandibular molars 
• 
No previous root canal therapy on the tooth in question 
• 
Able to complete the endodontic treatment in one visit 
 
The exclusion criteria: 
• 
Maxillary teeth, mandibular anteriors and premolars 
• 
Infection (swelling, sinus tract) on the tooth in question 
• 
Periodontal disease on the tooth in question 
• 
Dental trauma 
• 
Crown/ root fractures 
• 
Bone marrow transplant or other organ transplant patients who are on chemical 
immunosuppressants 
• 
Uncontrolled HIV disease 
• 
Patients at risk for delayed or compromised wound healing 
Note: Patients who are HIV positive and taking ART with undetectable viral load and a CD4 cell 
count above 400 are not considered immunocompromised 
 
The group distribution treatment will be done by the investigators by computer-generated 
randomization (Research Randomizer). Patients will be randomly divided into two groups: 
(A) experimental group - patients will receive root canal and PBM treatment. 
(B) control group - patients will receive root canal and PBM sham treatment. 
 
Patients will be informed of the details of study procedures. They will have the opportunity to 
ask questions. The consent form will be presented and discussed with patients and should be 
signed before the procedure. A single calibrated operator will perform all of the treatments (root 
canal therapy, PBM, and PBM sham treatments). 
 
Pre-treatment pain assessment 
The operator will ask the patient to rate pain level before starting the endodontic treatment. 
A Visual Analogue Scale (VAS) will be provided to the patient and is used as a pictorial tool 
to help patients quantify their pain level: 1-3 = mild pain; 4-6 = moderate pain; 7-10 = severe 
pain. (Figure 1) 

IRB NUMBER: HSC-DB-21-0579 
IRB APPROVAL DATE: 09/14/2021 
 
 
 
Figure 1. Illustration of the Visual Analogue Scale (VAS). 
 
Endodontic Treatment 
 
Patients will be anesthetized using 1.76 ml of 0.5% marcaine with 1:200,000 epinephrine via 
inferior alveolar nerve block, 1.76 mL 2% lidocaine with 1:100,000 epinephrine via inferior 
alveolar nerve block, and 1.76 mL of 4% Articaine with 1:200,000 epinephrine via infiltration. 
 
Conventional endodontic treatment will be performed as follows: radiographs, dental dam 
isolation, straight-line access, cavity preparation, working length determined using an electronic 
apex locator, and a #10 K file. Canals will be prepared using Vortex Blue rotary instrumentation 
with 0.04 taper according to manufacturer's instructions and the #10 K file used for patency at 
the beginning of the procedure. 
Irrigation will be performed with 10 mL of 6% sodium hypochlorite with in-and-out pecking 
motions, and a final rinse using 5 mL of 17% EDTA for 1 minute followed by 4 mL of 6% 
NaOCl for 1 minute. Irrigant activation will be completed prior to final rinse using an XP Endo 
Finisher (FKG Dentaire. La-Chaux-de-Fonds, Switzerland) file for 60 seconds using slight in- 
and-out movements. 
After root canal preparation, the root canals will be dried with paper points and filled using 
matched single cones and CeraSeal(MetaBiomed, America) – a calcium silicate-based sealer. 
Final radiograph will confirm final canals obturation. 
The pulp chamber will be etched with 35% phosphoric acid for 15 seconds, rinsed and gently 
dried, bonding agent (OptiBond® Solo Plus™, Kerr Corporation, Brea, CA, USA) will be 
applied, gently air-dried and light-cured for 20 seconds. Permaflo purple (Ultradent, America) 
composite resin will be used to seal the canals and light-cure for 20 seconds. Tooth will be 
restored with a glass ionomer (Fuji IX, GC America, USA) to seal the access cavity using a bulk 
fill technique. 
 
Photobiomodulation Treatment 
 
Immediately after the endodontic treatment, PBM therapy or sham will be performed using 
a 660 nm diode laser (SiroLaser Advance Plus, Dentsply Sirona Inc, Charlotte, NC, USA), with 
an 8mm tip diameter. The laser tip will be placed on the following external surfaces in a contact 
mode: mesiobuccal, distobuccal, mesiolingual and distolingual (Figure 1). The power output of 
the laser will be 50mW and will be verified by Power Meter (PM600 Power/Energy meter, 

IRB NUMBER: HSC-DB-21-0579 
IRB APPROVAL DATE: 09/14/2021 
 
Molectron Detector Inc, Portland, OR, USA). Each site will be irradiated for 25 s with an energy 
density of  10 J/cm2   . 
For the PBM sham similar procedure will be performed without activating the laser. 
 
 
Figure 2. Illustration of laser tip positioning 
 
Patient Dismissal 
At the completion of treatment, patients will be given both verbal and written post-op 
instructions along with a pain diary form to be completed at home (Figure 3). No pain 
measurement will be taken after the procedure as the patient is anesthetized. Assuming no 
contraindications patients will be instructed to take 400 mg Ibuprofen with 500mg extra strength 
Tylenol as needed for pain. If another pain medication is to be administered the reason will be 
well documented and the patients VAS scores may be excluded as this could be a potential 
confounding variable. All dosages of pain medication will be recorded. 
 
If patients are experiencing severe pain it will be recommended to take 400 mg Ibuprofen with 
500 mg extra strength Tylenol. If a subject cannot be reached at a specific time point they will 
simply be asked to recall to the best of their ability their pain score at that time level when they 
are reached. If a patient continually cannot recall their VAS score or stops responding their data 
will be excluded. 
 
Outcome Measures 
Patient pain as assessed by score on pain scale (see visual analog scale below), end of follow up 
period is 6 months. Patients will be asked for their pain scale responses at 6 hr, 12hr, 24hr, and 
72 hrs after treatment is completed. 
 
Primary outcome measure: Patient pain as assessed by score on pain visual analogue scale at 72 
hours 
 
Secondary outcome measures: Patient pain as assessed by score on pain visual analogue scale at 
6hrs, 12hrs, 24hrs 

IRB NUMBER: HSC-DB-21-0579 
IRB APPROVAL DATE: 09/14/2021 
 
 
 
 
Figure 3. Pain Diary Form to be completed by the patient at home. 
 
Post-treatment pain assessment 
 
Patients will be contacted via phone at 6, 12, 24, and 72-hour intervals. The pain level will be 
recorded by a blinded investigator. In addition, patients will be asked to self-report any pain 
medication intake. 
 
Risks and benefits 
 
Risks are minimal as photobiomodulation has not been shown to have any negative effects on the 
teeth and it potentially can reduce pain and improve healing after root canal therapy. 
 
Photobiomodulation will be performed using a 660nm red laser, which may have eye hazard 
risks. All safety protocols will be followed including laser safety wavelength-specific goggles by 
everyone in the operatory including the patient. The operator is laser certified and has been 
trained in laser safety protocols. 
 
Study Population  

IRB NUMBER: HSC-DB-21-0579 
IRB APPROVAL DATE: 09/14/2021 
 
Patients, 18 years and older, with symptomatic apical periodontitis (SAP) receiving endodontic 
treatment in one visit from the UT Health Science Center, Graduate Endodontic Dental Clinic. 
 
Data and Safety Monitoring  
 
No adverse effects are expected. All patients will be de-identified. During the study, data will be 
securely stored on encrypted computers or in a locked file cabinet with access limited to study 
personnel. Subject confidentiality and anonymity will be maintained throughout the study. 
 
Statistics  
 
Statistics to analyze collected data will include a 95% confidence interval of mean outcome 
measures that will be calculated for each treatment group. The significant level for the statistical 
test will be p < 0.05. 
 
Publication Plan  
 
Results will be submitted to a professional journal for consideration for publication. 
 
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