Acute Effects of LLLT on Pain Threshold and Pain Tolerance

Examining of the Acute Effects of Low-Level Laser Therapy (LLLT) on Pain Threshold and Tolerance: a Randomized Controlled Trial

Pain is defined by the International Association for the Study of Pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage." Low-Level Laser Therapy (LLLT) has gained attention as a safe, noninvasive intervention with analgesic and anti-inflammatory effects. This study examines whether a single session of LLLT can produce immediate changes in pain threshold and pain tolerance in healthy adults, compared to a sham laser control.

Study Overview

• Status: Recruiting
• Conditions: Acute Pain; Pain Threshold; Low-level Laser Therapy; Pain Tolerance; LLLT vs Sham
• Intervention / Treatment: Device: Low-Level Laser Therapy (LLLT); Other: Sham LLLT

Detailed Description

Pain is defined by the International Association for the Study of Pain 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 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. However, when inadequately controlled, it may induce central sensitisation and predispose patients to chronic pain syndromes. To address acute pain non-pharmacologically, physiotherapists typically employ a multimodal approach, including Transcutaneous Electrical Nerve Stimulation (TENS), which harnesses sensory-level stimulation to activate spinal inhibitory circuits and dampen pain signals; therapeutic ultrasound (US), where mechanical vibration and mild thermal effects accelerate inflammatory resolution and collagen synthesis; cryotherapy and thermotherapy, which modulate local tissue temperature to reduce nociceptor excitability and optimize perfusion; and manual therapy, including joint mobilization, soft tissue techniques, and muscle energy methods, that elicit both mechanical and neurophysiological analgesia, improving range of motion and function.

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 physiotherapy: High-Intensity Laser Therapy (HILT) and Low-Level Laser Therapy (LLLT). HILT operates at higher power outputs and can penetrate deeper tissues, producing photothermal effects. In contrast, LLLT, also termed photobiomodulation or cold laser therapy, uses lower power levels and longer exposure times, primarily inducing photochemical and photobiological changes without significant heating. LLLT is favoured for its safety and gentle stimulation of tissue repair across a wide range of conditions.

LLLT involves the application of red or near-infrared light, typically between 600 and 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.

The mechanisms underlying LLLT are thought to involve the absorption of photons by cellular chromophores, particularly cytochrome c oxidase in the mitochondria. This enhances mitochondrial respiration and ATP production, modulates reactive oxygen species, and induces transcription factors that promote cell survival and tissue repair. These effects may also extend to modulation of the autonomic nervous system, where LLLT has been shown to promote parasympathetic activity and reduce sympathetic dominance, contributing to analgesic and anti-inflammatory outcomes.

In clinical research, participants' expectations can influence perceived outcomes, a phenomenon known as the placebo effect. Placebo responses can elicit real neurophysiological changes, including activation of endogenous opioid and dopamine pathways and modulation of pain-related brain regions . To differentiate the specific effects of LLLT from expectancy-driven improvements, a sham-controlled design is essential, where participants undergo an identical procedure without therapeutic laser emission.

Despite the growing use of LLLT for pain management, there remains a research gap regarding its immediate effects on pain perception in healthy individuals. Much of the existing evidence focuses on chronic pain populations or multiple-session interventions. It remains unclear whether a single application of LLLT can immediately alter pain threshold or pain tolerance. Pain threshold is the lowest intensity at which a stimulus is perceived as painful, while pain tolerance is the maximum intensity an individual can endure. These measures provide complementary and objective indices of analgesic effects.

This study focuses on nociceptive pain in healthy adults, using standardised external stimulation to assess changes in pain threshold and pain tolerance following a single session of LLLT compared to a sham control.

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.

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yara Mabrouk Houtar; Phone Number: +905338875012; Email: yaramabrouk334@gmail.com
• Study Contact Backup: Name: Asst. Prof. Dr. Beraat Alptuğ Alptuğ; Email: balptug@eul.edu.tr

Study Locations

• Cyprus
  • Northern Cyprus
    • Lefka, Northern Cyprus, Cyprus, 99780
      • Recruiting
      • European University of Lefke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age between 18 and 35 years
• Healthy individuals without chronic medical conditions
• Free from chronic or acute pain
• All genders
• Able to provide informed consent

Exclusion Criteria:

• Menstruation at the time of testing
• Sensory deficits (failure to pass sharp-dull test)
• Pregnancy
• History of epilepsy
• Presence of cardiovascular conditions (including pacemaker)
• Acute hand injuries
• Diagnosed neurological disorders
• Use of analgesics or NSAIDs within the previous 48 hours
• Contraindications to low-level laser therapy or electrical stimulation (e.g., light sensitivity, malignancy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Level Laser Therapy (LLLT); Participants in this group will receive active Low-Level Laser Therapy (LLLT) using a 904 nm wavelength Chattanooga model 422 laser device at 1000 Hz. The laser will be applied for 2 minutes per point to three standardized points over the medial epicondyle region (total of 6 minutes). The energy dose is 0.9 J/cm². All participants and the researcher will wear appropriate laser safety eyewear.	Device: Low-Level Laser Therapy (LLLT); Active LLLT delivered via a 904 nm wavelength Chattanooga model 422 laser at 1000 Hz with a dosage of 0.9 J/cm². The laser is applied for 2 minutes per point over three standardized points near the medial epicondyle (total duration 6 minutes). Standard laser safety eyewear used for both participant and researcher.
Placebo Comparator: Sham LLLT; Participants in this group will undergo the same procedure, positioning, device placement, application duration, and safety eyewear use as the active LLLT group; however, the laser device will be deactivated. No therapeutic light energy will be delivered. This sham procedure is used to control for placebo and expectation effects.	Other: Sham LLLT; This is a sham comparator intervention. The procedure replicates the active Low-Level Laser Therapy (LLLT) protocol, including device placement, duration (6 minutes), and use of laser safety eyewear. However, the laser emission is deactivated, and no therapeutic light energy is delivered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrical Pain Threshold Intensity (mA)	Electrical pain threshold will be measured using tetanic faradic stimulation with gradual increases in current intensity. The cathode will be placed on the palmar surface of the third finger and the anode over the medial epicondyle. Participants will verbally indicate the point at which the electrical sensation is first perceived as painful. The stimulation intensity (in milliamperes) at this point will be recorded.	Pre-intervention and immediately post-intervention
Electrical Pain Tolerance Intensity (mA)	Electrical pain tolerance will be measured using tetanic faradic stimulation using the same electrode placement and stimulation parameters. Participants will verbally indicate the maximum level of pain they are willing to tolerate. The stimulation intensity (in milliamperes) at this point will be recorded.	Pre-intervention and immediately post-intervention

Collaborators and Investigators

• Sponsor: European University of Lefke
• Investigators: Principal Investigator: Asst. Prof. Dr. Beraat Alptuğ, European University of Lefke

Publications and helpful links

General Publications

• World Health Organization (WHO). Safety guidelines for low-level laser therapy. WHO Press; 2017.
• International Association for the Study of Pain (IASP). IASP announces revised definition of pain. 2020. https://www.iasp-pain.org/publications/news/announcement-of-revised-definition-of-pain
• Hashmi JT, Huang YY, Sharma SK, Kurup DB, De Taboada L, Carroll JD, Hamblin MR. Effect of pulsing in low-level light therapy. Lasers in Surgery and Medicine. 2010;42(6):450-466. https://doi.org/10.1002/lsm.20950
• Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophysics. 2016;3(3):337-361. https://doi.org/10.3934/biophy.2016.3.337
• Fan T, Li Y, Wong AYL, Liang X, Yuan Y, Xia P, Fu SN. 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. 2024;36(1):203-212. https://doi.org/10.1007/s40520-024-02853-0
• Glazov G, Yelland M, Emery J. Low-level laser therapy for chronic non-specific low back pain: A systematic review and meta-analysis. Lasers in Medical Science. 2021;36(2):249-259. https://doi.org/10.1007/s10103-020-03172-2
• Dundar U, Turkmen U, Toktas H, Ulasli AM, Solak O, Evcik D. 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. 2015;30(7):2327-2333. https://doi.org/10.1007/s10103-015-1806-5
• Chow RT, Johnson MI, Lopes-Martins RAB, Bjordal JM. 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. 2009;374(9705):1897-1908. https://doi.org/10.1016/S0140-6736(09)61522-1
• Alfredo PP, Bjordal JM, Dreyer SH, Meneguzzo DT, Pagnoncelli RM, Lopes-Martins RAB. Efficacy of low-level laser therapy associated with exercises in the treatment of shoulder disorders: A randomized controlled trial. Clinical Rehabilitation. 2009;23(9):889-897. https://doi.org/10.1177/0269215509337440

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: January 20, 2026
• First Submitted That Met QC Criteria: February 12, 2026
• First Posted (Actual): February 19, 2026

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Photobiomodulation; Pain Threshold; Acute Pain; Sham Laser; Low-Level Laser Therapy LLLT; Pain Tolerance; Analgesic Effect; Physiotherapy Modalities
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Acute Pain; Therapeutics; Laser Therapy; Phototherapy; Low-Level Light Therapy
• Other Study ID Numbers: BAYEK057.11

Plan for Individual participant data (IPD)

Study Data/Documents

1. Individual Participant Data Set
   Information comments: Individual participant data will not be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No