Examining of the Acute Effects of Low-Level Laser Therapy (LLLT) on Pain Threshold and Tolerance: a Randomized Controlled Trial
Phase: NA
Conditions: Pain Threshold, Pain Tolerance, Acute Pain, Low-level Laser Therapy, LLLT vs Sham
Sponsor: European University of Lefke

 
 
 
 
PT.YARA HOUTAR 
 
 
Examining the Acute Effects of Low-Level 
Laser Therapy (LLLT) on Pain Threshold and 
Pain Tolerance: A Randomized Controlled Trial 
European University of Lefke Protocol 
Record BAYEK057.11 
Document Date: 
10 February 2026 

 
 
 
 
PT.YARA HOUTAR 
 
 
Thesis Title 
Examining of the acute effects of Low-Level Laser Therapy (LLLT) on pain threshold and 
tolerance: a randomized controlled trial 
Research Problem, Aim, and Significance 
 
Introduction 
Pain is defined by the International Association for the Study of Pain (IASP, 2020) as “an unpleasant 
sensory and emotional experience associated with, or resembling that associated with, actual or potential 
tissue damage.” Pain can be classified into several types: nociceptive pain, neuropathic pain, and 
nociplastic pain. Nociceptive pain results from actual or potential damage to non-neural tissue and is 
due to the activation of nociceptors. It is typically acute and arises from injury, inflammation, or 
mechanical stimuli. Neuropathic pain, on the other hand, is caused by damage or disease affecting the 
somatosensory nervous system. Nociplastic pain involves altered nociception despite no clear evidence 
of tissue damage or nerve injury. 
Acute nociceptive pain is one of the most common presentations in musculoskeletal conditions and plays 
a crucial protective role by alerting the body to tissue damage and prompting healing responses.(Woolf, 
2010) However, when inadequately controlled, it may induce central sensitization and predispose 
patients to chronic pain syndromes. To address acute pain non-pharmacologically, physiotherapists 
typically employ a multimodal approach: Transcutaneous Electrical Nerve Stimulation (TENS), which 
harnesses sensory-level stimulation to activate spinal inhibitory circuits and dampen pain signals 
(Khadilkar et al., 2020); therapeutic ultrasound (US), where mechanical vibration and mild thermal 
effects accelerate inflammatory resolution and collagen synthesis (Uddin et al., 2021); cryotherapy and 
thermotherapy, which modulate local tissue temperature to reduce nociceptor excitability and optimize 
perfusion (Jinnah et al., 2019; Chen et al., 2024); and manual therapy—including joint mobilization, 
soft-tissue 
techniques, 
and 
muscle-energy 
methods—that 
elicits 
both 
mechanical 
and 
neurophysiological analgesia, improving range of motion and function (Serrano-García et al., 2025). 
More recently, laser therapy has emerged as a powerful adjunct for acute pain relief. Laser therapy refers 
to the medical use of specific light wavelengths to elicit therapeutic effects in tissues. Broadly, there are 
two main types used in Pysiotherapy: High-intensity laser therapy (HILT) and Low-Level Laser Therapy 
(LLLT). HILT operates at higher power outputs (typically >500 mW) and can penetrate deeper tissues, 
producing photothermal effects. In contrast, LLLT (also termed photobiomodulation or cold laser 
LEFKE EUROPEAN UNIVERSITY  
GRADUATE EDUCATION,  
TEACHING AND RESEARCH INSTITUTE 
 
 

 
 
 
 
PT.YARA HOUTAR 
 
therapy) uses lower power levels and longer exposure times, primarily inducing photochemical and 
photobiological changes without significant heating . LLLT is favored for its safety and gentle 
stimulation of tissue repair in a wide range of all conditions.  
LLLT, involves the application of red or near-infrared light (typically 600–1100 nm) at low intensities 
to avoid thermal effects. It has been widely adopted in clinical practice due to its non-invasive nature, 
minimal side effects, and effectiveness in reducing pain, promoting wound healing, and modulating 
inflammation (Lang-Illievich et al., 2020; Lawrence, 2024). 
The mechanisms underlying LLLT are generally thought to involve the absorption of photons by cellular 
chromophores, most notably cytochrome c oxidase in the mitochondria, which in turn enhances 
mitochondrial respiration and ATP production, modulation of reactive oxygen species, and the induction 
of transcription factors that promote cell survival and tissue repair (Arslan et al., 2018; Lawrence, 2024). 
These cellular effects may also extend to modulation of the autonomic nervous system, where LLLT 
has been shown to promote parasympathetic activity and reduce sympathetic dominance, potentially 
contributing to its overall analgesic and anti-inflammatory outcomes (Chow et al., 2011; Laakso & 
Burke, 2019). 
In clinical research, it is well established that participants’ expectations can influence perceived 
outcomes, a phenomenon known as the placebo effect. The placebo effect refers to improvements in 
symptoms resulting from an individual’s belief that they are receiving an active treatment, rather than 
from the treatment itself (Niazi, 2024). In pain research, placebo responses can elicit real 
neurophysiological changes, including activation of endogenous opioid and dopamine pathways, 
modulation of pain-related brain regions, and alterations in peripheral nociceptive processing (Blythe et 
al., 2023). These effects can significantly influence subjective measures of pain, such as pain threshold 
and tolerance, and may confound the assessment of an intervention’s true efficacy. Therefore, to 
differentiate the specific effects of LLLT from expectancy-driven improvements, it is essential to 
include a sham (placebo) control group, in which participants undergo a procedure identical to the active 
treatment but without therapeutic laser emission. This design strengthens the internal validity of the 
study by controlling for placebo effects and allowing for accurate evaluation of LLLT’s immediate 
analgesic properties. 
These effects are all relevant to pain: reduced inflammation and faster tissue repair can indirectly 
alleviate pain, and direct neural effects can alter pain signaling. Indeed, a body of evidence indicates 
that LLLT has clinically significant analgesic properties. Studies in various conditions such as 
(orthopedic injuries, rheumatologic diseases, and neuropathic pain syndromes) have shown that LLLT 
helps reduce pain. For instance, photobiomodulation has been successfully used to relieve 
musculoskeletal pain (such as neck and knee pain) and to accelerate recovery in sports injuries, often 

 
 
 
 
PT.YARA HOUTAR 
 
leading to improvements in patients’ pain ratings and functional outcomes (Hamblin, 2018). The appeal 
of LLLT in physiotherapy is further enhanced by its safety profile; it is generally well tolerated with 
minimal side effects, making it a useful adjunct or alternative to pharmacological analgesics in certain 
scenarios (Hamblin, 2018; Awatani et al., 2021). 
Despite the growing use of LLLT for pain management, there remains a notable gap in the research 
literature regarding its immediate effects on pain perception in healthy, pain-free individuals. Much of 
the existing evidence for LLLT’s analgesic efficacy comes from clinical studies on patients with chronic 
pain or from experiments measuring outcomes like visual analog scale (VAS) pain ratings, often after a 
series of treatment sessions (Hamblin, 2018; Awatani et al., 2021). These studies have established that 
LLLT can reduce pain over the course of days or weeks for various conditions. However, it is still 
unclear whether a single, brief application of LLLT can produce a meaningful change in an individual’s 
pain threshold or pain tolerance in the immediate term. Pain threshold refers to the lowest intensity at 
which a stimulus is perceived as painful, while pain tolerance is the maximum intensity a person can 
endure. These measures are critical in evaluating the efficacy of analgesic interventions (Russo et al., 
2018; Cimpean & David, 2019).Assessing both is important because they provide objective, 
complementary indices - threshold indexing sensory detection and tolerance indexing affective–
motivational endurance - and both are well suited to detect immediate, single-session hypoalgesic effects 
and to inform possible peripheral or central mechanisms (Rolke et al., 2006). 
In our study, we focus primarily on nociceptive pain, as the pain stimulus and measurement in this 
protocol target the activation of peripheral nociceptors through external stimulation in healthy 
individuals. Thus, understanding changes in nociceptive threshold and tolerance is central to evaluating 
the immediate analgesic effects of LLLT.` 
Aim: 
To assess the immediate effect of a single session of Low-Level Laser Therapy (LLLT) versus sham-
control on pain threshold and pain tolerance in healthy adults. 
Hypotheses: 
Hypothese 1: 
H0: There is no significant change in pain threshold and pain tolerance between the LLLT group and 
the sham-control group immediately after intervention. 
H1: There is significant change in pain threshold and pain tolerance between the LLLT group and the 
sham-control group immediately after intervention. 
Hypothese 2: 

 
 
 
 
PT.YARA HOUTAR 
 
H0: There is no significant pre-to-post change in pain threshold and pain tolerance within the LLLT 
group.  
H1: There is significant pre-to-post change in pain threshold and pain tolerance within the LLLT group. 
Hypothese 3: 
H0: There is no significant pre-to-post change in pain threshold and pain tolerance within the sham-
control group.  
H1: There is significant pre-to-post change in pain threshold and pain tolerance within the sham-control 
group.  
 
Method  
 
Methodology 
Study Design;  
This is a randomized, sham-controlled trial with a parallel-group, two-arm, superiority design, using a 
1:1 allocation ratio. 
Study site and population 
The universe of this study will consist of healthy adult individuals who are currently enrolled at, or 
employed by, the European University of Lefke (EUL), Faculty of Health Sciences, located in the 
Turkish Republic of Northern Cyprus (TRNC). These individuals will represent a non-clinical 
population suitable for evaluating the acute effects of LLLT on experimentally induced pain responses, 
specifically pain threshold and pain tolerance levels. 
The accessible population will include volunteers from the Department of Physiotherapy and 
Rehabilitation, as well as other departments within the university who meet the inclusion criteria.  
All participants of the study will be informed about the research, and their verbal and written consent 
will be obtained (Appendix 1 and 2). Healthy adult volunteers will be recruited. Data collection will 
take place in the department’s Physiotherapy and Rehablitation units. 
After obtaining ethical approval, the study will start in October 2025, and participant recruitment and 
data collection will run from October 2025 to January 2026. 
Randomization and blinding technique  

 
 
 
 
PT.YARA HOUTAR 
 
All eligible participants are randomly assigned to one of two groups - (LLLT) group or the Sham-control 
group in a 1:1 ratio using computer-generated randomization. The allocation sequence is sealed in 
opaque envelopes. This study will be conducted using a single-blind design. Participants will be blinded 
to the group allocation. The participants will not be informed whether they are receiving active LLLT 
or sham laser treatment. To maintain blinding integrity, only the researcher administering the 
interventions will have access to the randomization codes, which will be concealed until the completion 
of data analysis. 
 
Inclusion Criteria 
 
Age between 18 and 35 years. 
 
Healthy individuals without any chronic medical conditions. 
 
Free from both chronic and acute pain at the time of participation. 
 
All genders will be included to ensure broader generalizability of results. 
Exclusion Criteria 
 
Menstruation at the time of testing, to minimize variability in pain perception related to 
hormonal fluctuations. 
 
Sensory deficits, such as failure to pass the sharp–dull discrimination test, to confirm intact 
somatosensory function. 
 
Pregnancy, due to safety considerations and physiological changes affecting pain perception. 
 
History of Epilepsy. 
 
Presence of cardiovascular conditions, including cardiac pacemakers. 
 
Acute hand injuries (e.g., fractures or recent trauma). 
 
Diagnosed neurological disorders. 
 
Use of analgesic or non-steroidal anti-inflammatory drugs (NSAIDs) within the previous 48 
hours, as these may influence autonomic responses and alter pain perception. 
 
Any contraindications to the application of LLLT or electrical stimulation (e.g., epilepsy, 
malignancy, light sensitivity). 

 
 
 
 
PT.YARA HOUTAR 
 
Sample Size and Sampling Technique 
The study population will include healthy adults aged 18–35 years from the European University of 
Lefke, Faculty of Health Sciences. Participants will be selected through voluntary recruitment and 
screened according to predefined inclusion and exclusion criteria. The sample size was estimated using 
G*Power (v3.1.9.4 for Mac) for a 2 × 2 mixed repeated-measures ANOVA (within-factor = Time [pre, 
post]; between-factor = Group [LLLT, Sham]). Assuming a moderate effect size (f = 0.25), α = 0.05, 
power (1 – β) = 0.80, and correlation among repeated measures r = 0.5, the required total sample was 
calculated as 52 participants (26 per group). This size provides adequate power to detect significant 
Group × Time interactions in pain-threshold and pain-tolerance measures, consistent with similar LLLT 
studies in healthy volunteers (Chow et al., 2009; Dundar et al., 2015; Alfredo et al., 2009). 
Research Variables: 
Dependent Variables: 
Dependent variables are: Pain Threshold and Pain Tolerance. 
Independent Variables: 
Independent variables are: Age, Gender, Height, Weight, Body Mass Index (BMI), Dominant 
Hand, and Occupation. 
These variables will be measured pre- and post-intervention to evaluate the effects of LLLT. 
Data Collection Tools: 
Demographic Information Form (see Appendix 3,4) 
This form gathers essential participant details such as age, gender, dominant hand, occupation, 
anthropometric measurements (height, weight, BMI), history of pain, and any contraindications for laser 
or electrical stimulation. 
Pain Assessment (see Appendix 5) 
Pain threshold and tolerance will be assessed via tetanic faradic stimulation with gradual current increase 
in current intensity. Participants will provide verbal feedback to indicate initial pain perception and their 
maximum tolerance level. Throughout the procedure, The researcher will actively monitor the procedure 
and ask participants about their sensations during the electrical stimulation to ensure accurate reporting. 
Electrode placement and stimulation parameters will follow a standardized protocol to ensure 
consistency. 

 
 
 
 
PT.YARA HOUTAR 
 
Pain Assessment Protocol: 
 
Before starting the assessment, a sharp/dull sensory test will be performed on the dominant hand to 
confirm intact cutaneous sensation and to ensure that participants are able to provide reliable feedback. 
Participants who demonstrate impaired sensory perception will not proceed further. 
 
Pain threshold and tolerance will then be evaluated before and after LLLT(or shamLLLT) using tetanic 
faradic stimulation delivered by a Enraf Nonius IONOPULSIS 4192 electrotherapy unit (Doğuluer, 
Gurses, Demir, & Ozyilmaz, 2003). 
Electrode placement: 
 
Cathode: will be placed on the palmar surface of the third finger of the dominant hand. As an active 
electrode pen electrode will be used. 
 
Anode : will be positioned over the medail epicondyle of the same arm. As an passive electrode 
disposable electrode (15*5cm) will be used. 
 
This placement is chosen to follow the pathway of the median and radial nerves, allowing for 
consistent stimulation and reliable assessment of pain perception (Jiang, Muceli, Graimann, & Farina, 
2011). 
 
A new set of self-adhesive electrodes will be applied for each participant to maintain hygiene and 
standardization. 
Stimulation parameters: 
Current type: tetanic faradic current 
Pulse duration: 1 ms 
Interpulse interval: 20 ms 
Intensity: will be increased gradually at a rate of 0.1 mA/sec 
Stimulation time will be continuously monitored by the researcher. 
Assessment procedure: 
Participants will be instructed to provide verbal feedback at two points during stimulation: 
Pain threshold: Point at which sensation becomes painful. 
Pain tolerance: Maximum tolerable level of pain. 
The researcher will supervise the procedure throughout, monitor participant responses, and ask about 
the sensations experienced to ensure accuracy and reliability of the data collected. 
 
Interventions 
Participants will be randomly assigned two groups. LLLT group will receive laser treatment, sham-
control group will have same prosedures without the activation of the LLLT. 

 
 
 
 
PT.YARA HOUTAR 
 
LLLT group 
LLLT will be applied using a 904 nm wavelength laser device. The parameters and treatment procedure 
are as follows: 
Device: Chattanooga model no. 422. 
Frequency: 1000 Hz 
Dosage: 0.9 J/cm² 
Application time: 6 minutes total (2 minutes per point) 
Number of points: 3 points 
Treatment area: Medail epicondyle region, targeting the ulnar and median nerve pathways for 
standardized application. 
During all applications, both the participant and the researcher will wear protective laser safety glasses 
to ensure safety and prevent accidental exposure. A consistent protocol will be followed for all 
participants to ensure treatment reliability and reproducibility. 
Sham LLLT protocol: Participants in the sham group will receive the same device placement and 
application duration as the active group, but the laser output will be switched off. and participants will 
wear the same safety goggles. This sham procedure maintains blinding while delivering no therapeutic 
laser energy. 
Sham-control group 
Participants in the sham laser treatment group will undergo the same treatment protocol as the LLLT 
group; however, the laser device will be deactivated or set to emit no therapeutic dose. This procedure 
ensures that participants experience similar interactions and procedures without receiving active 
treatment, thereby maintaining blinding and controlling placebo effects. 
Post-treatment Pain Reassessment: 
Both groups will receive the same faradic stimulation protocol will be repeated after the intervention 
(active or sham) to reassess pain threshold and tolerance. 
Statistical Analysis 
 

 
 
 
 
PT.YARA HOUTAR 
 
Data will first be screened for accuracy, missing values, and outliers. The Shapiro–Wilk test and 
Levene’s test will be used to examine the assumptions of normality and homogeneity of variances, 
respectively. Descriptive statistics will be presented as mean ± standard deviation or median (min–max) 
for continuous variables, and as frequency (percentage) for categorical variables. The main analysis will 
be conducted using a 2 × 2 mixed repeated-measures ANOVA, with Group (LLLT vs Sham) as the 
between-subjects factor and Time (Pre vs Post) as the within-subjects factor. The Group × Time 
interaction will be the primary focus, indicating whether treatment-related changes in pain threshold and 
pain tolerance differ between the two groups. When significant effects are observed, Bonferroni-
adjusted pairwise comparisons will be performed to determine the direction of the differences. If the 
assumptions of normality or homogeneity of variances are violated, a nonparametric alternative will be 
applied. Specifically, the Aligned Rank Transform (ART) ANOVA procedure will be used, as it allows 
factorial analyses and interaction testing under nonparametric conditions. In cases where the ART model 
is not applicable, separate Wilcoxon signed-rank tests (for within-group comparisons) and Mann–
Whitney U tests (for between-group comparisons) will be performed. Effect sizes will be reported as 
partial eta squared (η²ₚ) for parametric analyses and as r for nonparametric tests. A p-value < 0.05 will 
be considered statistically significant in all tests. All statistical analyses will be performed using IBM 
SPSS Statistics (version 26 for Mac) and R (v4.3 for Mac). 
 
 
 
 
Appendices 
Appendix 1: Informed Consent(English) 
INFORMED CONSENT FORM 
You have been invited to take part in the study titled “Examining of the acute 
effects of Low-Level Laser Therapy (LLLT) on pain threshold and tolerance: 
a randomized controlled trial” This study is conducted for research purposes and 
participation is voluntary. After you have been fully informed about the study and 
your questions have been answered, you will be asked to sign this form if you wish 
to participate. This research is under the responsibility of Asst. Prof. Dr. Beraat 
ALPTUG from the Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, 
European University of Lefke. 
The aim of this study is to examine the immediate effects of Low-Level Laser Therapy (LLLT) on pain 
threshold and pain tolerance. Within the scope of our study, you will undergo assessment of pain 
perception through tetanic faradic stimulation before and after the application of LLLT. LLLT will be 
applied to the medail epicondyle region for a few minutes, following a standardized protocol by a 
physiotherapist. 
The researchers will use your personal information to conduct the research and statistical analysis, but 
your identity will be kept confidential. At the end of the study, you have the right to request information 

 
 
 
 
PT.YARA HOUTAR 
 
about your own results. The study results may be published in the medical literature at the end of the 
study, but your identity will not be disclosed. There will be no conflict of interest, such as the 
participation of individuals in the study in a physiotherapy program, which will provide financial support 
to any of the researchers at the end of the study. 
 
I have read the information that must be given to the volunteer before the research above. I have 
been given written explanations about these. Under these conditions, I agree to participate in the 
research with my own consent, without any pressure or coercion. 
Name-Surname:                                             
Date:   
 
 
 
Signature: 
Phone Number:                               
 
The researcher who made the written statements:    
 
Name-Surname: 
Phone Number: 
Signature: 
 
The person who gave the witness: 
Name-Surname: 
 
 
                                        
Phone Number: 
Signature:                                                                                        

 
 
 
 
PT.YARA HOUTAR 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 3: Demographic Information Form 
 
Age: ______ 
 
Gender: ☐ Male ☐ Female ☐other 
 
Dominant Hand: ☐ Right ☐ Left 
 
Occupation: ______________ 
 
Height : ______________ 
 
Weight: ______________ 
 
Body Mass Index (BMI):______________ 
 
 Do you have any history of acute or chronic pain? 
 ☐ No  ☐ Yes If yes, please specify: ________________________ 
 
Do you have any known contraindications for laser therapy or electrical stimulation? 
 ☐ No  ☐ Yes If yes, please provide details (e.g., pacemaker, pregnancy, epilepsy): 
 ______________________________________________________________ 
 
 

 
 
 
 
PT.YARA HOUTAR 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Appendix 5: Evaluation Record Table 
Test Phase 
Value (mA) Test Phase 
Value (mA) 
BTh (Before Threshold)  
ATh (After Threshold)  
BTt (Before Tolerance) 
 
ATt (After Tolerance) 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
PT.YARA HOUTAR 
 
References  
 
Alfredo, P. P., Bjordal, J. M., Dreyer, S. H., Meneguzzo, D. T., Pagnoncelli, R. M., & Lopes-Martins, 
R. A. B. (2009). Efficacy of low-level laser therapy associated with exercises in the treatment 
of shoulder disorders: A randomized controlled trial. Clinical Rehabilitation, 23(9), 889–897. 
https://doi.org/10.1177/0269215509337440 
Anders, J. J., Lanzafame, R. J., & Arany, P. R. (2015). Low-level light/laser therapy versus 
photobiomodulation therapy. *Photomedicine and Laser Surgery, 33*(4), 183–184. 
https://doi.org/10.1089/pho.2015.9848 
Arslan, H., Köseoğlu, S., Doğanay Yıldız, E., Arabacı, T., Savran, L., Yıldız, D. A., & Veyisoğlu, G. 
(2018). Effect of intracanal diode laser application and low-level laser therapy on CGRP 
change. Brazilian Oral Research, 32, e125. https://doi.org/10.1590/1807-3107bor-
2018.vol32.0125  
Blythe, J. S., Thomaidou, M. A., Peerdeman, K. J., van Laarhoven, A. I. M., van Schothorst, M. M. E., 
Veldhuijzen, D. S., & Evers, A. W. M. (2023). Placebo effects on cutaneous pain and itch: A 
systematic review and meta-analysis of experimental results and methodology. PAIN, 164(6), 
1181–1199. https://doi.org/10.1097/j.pain.0000000000003000 
By David N Taylor, Tyler Winfield, Shari WyndContainer: Journal of Chiropractic 
MedicinePublisher: Elsevier 
BVYear: 2020Volume: 19Issue: 2DOI: 10.1016/j.jcm.2020.06.002URL: https://pmc.ncbi.nlm.
nih.gov/articles/PMC7729198/  
By Javad T. Hashmi, Ying‐Ying Huang, Sulbha K. Sharma, Divya Balachandran Kurup, Luis De 
Taboada, James D. Carroll, Michael R. HamblinContainer: Lasers in Surgery and 
MedicinePublisher: WileyYear: 2010Volume: 42Issue: 6DOI: 10.1002/lsm.20950URL: https:/
/pmc.ncbi.nlm.nih.gov/articles/PMC2933784/ 
Chen, W., et al. (2021). Pulsed vs. continuous LLLT in acute pain: A randomized trial. Journal of 
Biophotonics, 14(3), e202000345. 
Chen, W., et al. (2021). Pulsed vs. continuous LLLT in acute pain: A randomized trial. Journal of 
Biophotonics, 14(3), e202000345. 
Chen, W., Zhang, Q., & Yu, J. (2021). Mechanisms of photobiomodulation in pain relief. *Journal of 
Biophotonics, 14*(3), e202000345. https://doi.org/10.1002/jbio.202000345 
Chow, R. T., et al. (2018). Penetration depth of 904 nm laser in musculoskeletal tissues. Lasers in 
Medical Science, 33(2), 123–130. 
Chow, R. T., et al. (2018). Penetration depth of 904 nm laser in musculoskeletal tissues. Lasers in 
Medical Science, 33(2), 123–130. 

 
 
 
 
PT.YARA HOUTAR 
 
Chow, R. T., Johnson, M. I., Lopes-Martins, R. A. B., & Bjordal, J. M. (2009). Efficacy of low-level 
laser therapy in the management of neck pain: A systematic review and meta-analysis of 
randomized placebo or active-treatment controlled trials. The Lancet, 374(9705), 1897–1908. 
https://doi.org/10.1016/S0140-6736(09)61522-1 
Cimino, R., Farella, M., Michelotti, A., Pugliese, R., & Martina, R. (2000). Does the ovarian cycle 
influence the pressure-pain threshold of the masticatory muscles in symptom-free women? 
Journal of Orofacial Pain, 14(2), 105–111.  
Cimpean, A., & David, D. (2019). The mechanisms of pain tolerance and pain-related anxiety in acute 
pain. Health Psychology Open, 6(2), 2055102919865161. 
https://doi.org/10.1177/2055102919865161  
Doğuluer, M., Gurses, H. N., Demir, R., & Ozyilmaz, S. (2003). Electrical pain threshold in patients 
with symptomatic and asymptomatic ischemic heart disease and healthy subjects. The Pain 
Clinic, 15(4), 381–384. https://doi.org/10.1163/156856903770196737 
Dundar, U., Turkmen, U., Toktas, H., Ulasli, A. M., Solak, O., & Evcik, D. (2015). Effect of low-level 
laser therapy on pain and function in patients with knee osteoarthritis: A double-blind, 
randomized controlled trial. Lasers in Medical Science, 30(7), 2327–2333. 
https://doi.org/10.1007/s10103-015-1806-5 
Effect of pulsing in low‐level light therapy By Javad T Hashmi, Ying‐Ying Huang, Sulbha K Sharma, 
Divya Balachandran Kurup, Luis De Taboada, James D Carroll, Michael R 
HamblinContainer: Lasers in Surgery and 
MedicinePublisher: WileyYear: 2015Volume: 42Issue: 6DOI: 10.1002/lsm.20950URL: https:/
/pmc.ncbi.nlm.nih.gov/articles/PMC2933784/ 
Fan, T., Li, Y., Wong, A. Y. L., Liang, X., Yuan, Y., Xia, P., ... & Fu, S. N. (2024). A systematic 
review and network meta-analysis on the optimal wavelength of low-level light therapy 
(LLLT) in treating knee osteoarthritis symptoms. Aging Clinical and Experimental Research, 
36(1), 203–212. https://doi.org/10.1007/s40520-024-02853-0  
Fillingim, R. B., Loeser, J. D., & Baron, R. (2016). Pain tolerance and threshold: A comprehensive 
review. *Pain Medicine, 17*(8), 1414–1425. https://doi.org/10.1093/pm/pnw046 
Glazov, G., Yelland, M., & Emery, J. (2021). Low-level laser therapy for chronic non-specific low 
back pain: A systematic review and meta-analysis. *Lasers in Medical Science, 36*(2), 249–
259. https://doi.org/10.1007/s10103-020-03172-2 
Hamblin, M. R. (2016). Mechanisms and applications of the anti-inflammatory effects of 
photobiomodulation. *AIMS Biophysics, 3*(3), 337–361. 
https://doi.org/10.3934/biophy.2016.3.337 
Huang, Z., et al. (2019). Pulsed LLLT inhibits TRPV1 in acute pain models. Pain Research & 
Management, 24(1), 1–9. 

 
 
 
 
PT.YARA HOUTAR 
 
International Association for the Study of Pain (IASP). (2020). *Terminology*. Retrieved from 
https://www.iasp-pain.org 
International Association for the Study of Pain (IASP). (2020, July 16). IASP announces revised 
definition of pain. https://www.iasp-pain.org/publications/news/announcement-of-revised-
definition-of-pain 
Karlekar, A., Bharati, S., & Saxena, Y. (2020). Low-level laser therapy in musculoskeletal pain: A 
review of mechanisms. *Journal of Clinical Orthopaedics and Trauma, 11*(Suppl 5), S675–
S680  https://doi.org/10.1016/j.jcot.2020.07.016 
Lang-Illievich, K., Winter, R., Rumpold-Seitlinger, G., Schicho, K., Dorn, C., Klivinyi, C., & 
Bornemann-Cimenti, H. (2020). The effect of low-level light therapy on capsaicin-induced 
peripheral and central sensitization in healthy volunteers: A double-blinded, randomized, 
sham-controlled trial. Pain and Therapy, 9(2), 717–726. https://doi.org/10.1007/s40122-020-
00205-0  
Lawrence, J. (2024). Photobiomodulation as medicine: Low-level laser therapy (LLLT) for acute 
tissue injury or sport performance recovery. Journal of Functional Morphology and 
Kinesiology, 9(4), 181. https://doi.org/10.3390/jfmk9040181 
Leal-Junior, E. C., et al. (2022). Photobiomodulation reduces oxidative stress and TRPV1 expression 
in athletes. Lasers in Medical Science, 37(1), 123–130. 
Leal-Junior, E. C., Vanin, A. A., & Tomazoni, S. S. (2022). Photobiomodulation reduces oxidative 
stress and TRPV1 expression in athletes. *Lasers in Medical Science, 37*(1), 123–130. 
https://doi.org/10.1007/s10103-021-03380-4  
LeResche, L., Mancl, L., Sherman, J. J., Gandara, B., & Dworkin, S. F. (2003). Changes in 
temporomandibular pain and other symptoms across the menstrual cycle. Pain, 106(3), 253–
261. https://doi.org/10.1016/j.pain.2003.08.001  
Low-Level Laser Light Therapy Dosage Variables vs Treatment Efficacy of Neuromusculoskeletal 
Conditions: Scoping Review 
Mense, S. (2019). Faradic current-induced pain: Mechanisms and applications. *Journal of Pain 
Research, 12*, 2345–2356. https://doi.org/10.2147/JPR.S214678  
Niazi, S. K. (2024). Placebo effects: Neurological mechanisms inducing analgesia. Healthcare, 
12(22), 2314. https://doi.org/10.3390/healthcare12222314 
Robertson, V., Ward, A., & Low, J. (2014). *Electrotherapy explained: Principles and practice*. 
Elsevier.   
Rolke, R., Baron, R., Maier, C., Tölle, T. R., Treede, R.-D., Beyer, A., … Wasserka, B. (2006). 
Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): 
Standardized protocol and reference values. Pain, 123(3), 231–243. 
https://doi.org/10.1016/j.pain.2006.01.041  

 
 
 
 
PT.YARA HOUTAR 
 
Russo, A., Coppola, G., Pierelli, F., Parisi, V., Silvestro, M., Tessitore, A., & Tedeschi, G. (2018). 
Pain perception and processing in individuals with migraine. Frontiers in Neurology, 9, 576. 
https://doi.org/10.3389/fneur.2018.00576  
Sluka, K. A., Bjordal, J. M., & Rakel, B. (2012). Electrical stimulation for pain relief: Mechanisms 
and clinical applications. *Journal of Pain Research, 5*, 1–12. 
https://doi.org/10.2147/JPR.S27621  
Woolf, C. J. (2010). What is this thing called pain? The Journal of Clinical Investigation, 120(11), 
3742–3744. https://doi.org/10.1172/JCI45178  
Woolf, C. J. (2010). What is this thing called pain? The Journal of Clinical Investigation, 120(11), 
3742–3744. https://doi.org/10.1172/JCI45178  
 World Health Organization (WHO). (2017). *Safety guidelines for low-level laser therapy*. WHO 
Press.   
 
 
 

 
 
 
 
PT.YARA HOUTAR