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Completed

NCT Number: NCT06967714

Disentangling the Variability of Exercise-induced Hypoalgesia: the Role of Circulatory Compounds

Physical exercise is increasingly recognized as an effective treatment for chronic pain. Studies in humans and animals have shown that a single session of exercise induces a reduction of sensitivity to experimental painful stimuli lasting up to 45 minutes. In a recent study conducted in our laboratory, we found (1) that this exercise- induced hypoalgesia (EIH) is mainly driven by local changes in muscle nociceptor sensitivity within exercising muscles and (2) that EIH is consistent at a group level but fluctuates across sessions within participants. The first aim of this project is to uncover the mechanism(s) that drive EIH by investigating whether processes that could contribute to an exercise-induced change in muscle nociceptor sensitivity match the fluctuating pattern of EIH. Specifically, we will assess the possible involvement in EIH of the endocannabinoid system (eCB), Kynurenic acid (KynA, a circulating myokine that transiently increases after exercise), and β -endorphins (βE). Using a sample of 90 healthy males and females aged 18 to 30 years, we will measure sensitivity to blunt pressure stimuli before, immediately after, and 45 min after a 25-min cycling exercise to assess muscle nociceptor sensitivity at exercising (rectus femoris muscle) and non-exercising (ventral forearm) muscles. Blood samples will be collected at these time-points to measure plasma levels of eCBs, βE, and KynA. In addition, the effect of sex on EIH is controversial: some studies report no differences between males and females, while others report a greater effect in males or in females. Therefore, a secondary aim of this study is to explore potential sex differences in the manifestation and underlying mechanism(s) of EIH.

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Key information

Conditions

Healthy Behavior Motor Activity Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–30 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

UCLouvain, Institute of neuroscience

Brussels, Belgium, 1200

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Males, or females using hormonal contraception since ≥ 3 months.
  • Aged between 18 and 30 years.
  • Ability to provide written informed consent.
  • Fluency in French or English.
  • BMI between 17 and 30 kg/cm2.

Exclusion criteria

  • Regular tobacco use (> 1/month)
  • Not willing or able to abstain from alcohol, recreational drugs, coffee, or tea from 24 hours prior to each experimental session.
  • Not willing or able to restrain from physical activity > 24h prior to each experimental session, and to be in a fasted state on the day of each experimental session.
  • Any evidence for neurological, cardiovascular, respiratory, inflammatory, endocrine, psychiatric, oncological, rheumatological conditions on direct questioning.
  • Presence of any medical devices (e.g., cardiac pacemaker) implants or prothesis unless it is beyond discussion that these will not put the subject's safety during the study at risk and will not interfere with the results of the study.
  • Any chronic pain condition or recent history thereof (i.e., within the preceding 2 years).
  • Wounds or skin alteration on testing sites.
  • Surgery < 12 months.
  • Any drug intake in the past 2 weeks including antibiotics, herbal medicines and other remedies except the following drugs that will be allowed up to 48 hours prior to the experiments: oral paracetamol or ibuprofen for a self-limiting condition (e.g. toothache, bruise). Oral antihistaminics and nasal aerosol and topical treatments for seasonal allergy up to 1 week before the experimental session.
  • Any physical activity contraindication.
  • Pregnancy.

Treatment and study plan

Exercise

Behavioral

25 min cycling exercise at 75% of hear rate reserve. Physical use of one upper-limb will be restricted with a sling.

Primary outcomes

  1. Pressure pain threshold

    Time frame: At each experimental experimental session (2 in total): before (T0), immediately after (T1), and 45 min (T2) after the intervention (cycling exercise).

    The investigators will use blunt pressure to preferentially activate the mechano-sensitive deep-tissue nociceptors. The stimuli will be delivered with a manual digital algometer with a contact surface area of 1cm2 (FPIX; Wagner Instruments, Greenwich, USA) connected to a laptop computer through a USB-serial port. A bespoke Matlab (The Mathworks, USA, mathworks.com) script will provide visual feedback of the force application rate to the examinator, while blinding him to the final threshold value. The participants will be asked to report the first onset of pain by pressing on a keyboard key, defining the pressure pain threshold (PPT). The procedure is safe, and there are no side effects to the stimulation

Secondary outcomes

  1. Plasmatic levels of endocannabinoids

    Time frame: At each experimental experimental session (2 in total): before (T0), immediately after (T1), and 45 min (T2) after the intervention (cycling exercise).

    Blood samples will be collected after catheterization of an upper limb vein. The investigators will collect blood samples before, immediately after, and 45 min after exercise (at each session) to investigate potential EIH contributors. Specifically,the plasmatic levels of the endocannabionid (anandamide and 2-Arachidonoylglycerol) will be measured.

  2. Plasmatic level of Kynurenic acid

    Time frame: At each experimental experimental session (2 in total): before (T0), immediately after (T1), and 45 min (T2) after the intervention (cycling exercise).

    Blood samples will be collected after catheterization of an upper limb vein. The investigators will collect blood samples before, immediately after, and 45 min after exercise (at each session) to investigate potential EIH contributors. Specifically, plasmatic levels of kynurenic acid will be measured.

  3. Plasmatic level of and beta-endorphin

    Time frame: At each experimental experimental session (2 in total): before (T0), immediately after (T1), and 45 min (T2) after the intervention (cycling exercise).

    Blood samples will be collected after catheterization of an upper limb vein. The investigators will collect blood samples before, immediately after, and 45 min after exercise (at each session) to investigate potential EIH contributors. Specifically, the plasmatic levels of beta-endorphins will be measured.

Sponsors and collaborators

Lead sponsor

Université Catholique de Louvain

Other

Registry information

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
May 13, 2025
Registry last updated
Jun 25, 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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