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Completed

NCT Number: NCT07422272

Acute Effects of LLLT on Pain Threshold and Pain Tolerance

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.

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Key information

Age range

18 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

European University of Lefke

Lefka, Northern Cyprus, 99780, Cyprus

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Low-level laser therapy (LLLT)

Device

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.

Sham LLLT

Other

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.

Primary outcomes

  1. Electrical Pain Threshold Intensity (mA)

    Time frame: Pre-intervention and immediately post-intervention

    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.

  2. Electrical Pain Tolerance Intensity (mA)

    Time frame: Pre-intervention and immediately post-intervention

    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.

Sponsors and collaborators

Lead sponsor

European University of Lefke

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Feb 19, 2026
Registry last updated
Jul 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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