An interventional study of Exercise in Healthy, sponsored by Université Catholique de Louvain. Completed at 1 site in Belgium. Open to participants aged 18 Years to 30 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-25.
Sponsored by Université Catholique de Louvain · Not applicable, Interventional, and Basic science
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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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
25 min cycling exercise at 75% of hear rate reserve. Physical use of one upper-limb will be restricted with a sling.
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
Time frame: At each experimental experimental session (2 in total): before (T0), immediately after (T1), and 45 min (T2) after the intervention (cycling exercise).
Plasmatic levels of endocannabinoids
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.
Time frame: 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
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.
Time frame: 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
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.
Time frame: At each experimental experimental session (2 in total): before (T0), immediately after (T1), and 45 min (T2) after the intervention (cycling exercise).
Plan to share: No
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Université Catholique de Louvain