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

NCT06967714 | Recruiting

• 1 other identifier: EIH-VAR
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

exercise-induced hypoalgesia; mechanisms; pain; exercise

Outcome Measures

Primary Outcomes (1)

• Pressure pain threshold

  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

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

Secondary Outcomes (3)

• Plasmatic levels of endocannabinoids

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

• Plasmatic level of Kynurenic acid

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

• Plasmatic level of and beta-endorphin

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

Study Arms (1)

Exercise

EXPERIMENTAL

Participants will complete three experimental sessions. In the first session, they will be asked to complete a set of questionnaires and to do a maximal exercise test. The next two sessions will be identical and will consist in blunt pressure sensitivity assessment-before (T0), immediately after (T1), and 45 min after (T2) a 25 min cycling exercise-at body parts involved (lower limb) and non-involved (upper limb, immobilized) in the exercise. Venous blood samples will be collected concomitantly to the sensory testing procedure.

Behavioral: Exercise

Interventions

Exercise BEHAVIORAL

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

Exercise

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Université Catholique de Louvain: lead

Study Sites (1)

UCLouvain, Institute of neuroscience

Brussels, Belgium, 1200, Belgium

RECRUITING

MeSH Terms

Conditions

Pain; Motor Activity

Interventions

Exercise

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

André Mouraux, MD, PhD, Professor

CONTACT

+3227645447; andre.mouraux@uclouvain.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: * Participant will be masked to study hypotheses * Outcome assessor/Investigator will be masked to sensory tests results
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Withi-subject desing. Participants will complete three experimental sessions. In the first session, they will be asked to complete a set of questionnaires and to do a maximal exercise test. The next two sessions will be identical and will consist in blunt pressure sensitivity assessment-before (T0), immediately after (T1), and 45 min after (T2) a 25 min cycling exercise-at body parts involved (lower limb) and non-involved (upper limb, immobilized) in the exercise. Venous blood samples will be collected concomitantly to the sensory testing procedure.

Study Record Dates

• First Submitted: April 22, 2025
• First Posted: May 13, 2025
• Study Start: April 14, 2025
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: May 21, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)