Sex Differences in Exercise-Induced Hypoalgesia

March 16, 2026 updated by: Álvaro Reina Varona, Centro Universitario La Salle

Sex Differences in Exercise-Induced Hypoalgesia Following Aerobic Exercise Using a Lower-Limb Cycle Ergometer: A Quasi-Experimental Study

Exercise-induced hypoalgesia (EIH) refers to the reduction in pain sensitivity following acute exercise. Although aerobic exercise has been shown to induce hypoalgesia in healthy individuals, it remains unclear whether the magnitude of this response differs between men and women.

This quasi-experimental study aims to evaluate sex differences in pressure pain thresholds following a standardized aerobic exercise protocol using a lower-limb cycle ergometer. Pressure pain thresholds will be assessed before exercise, immediately after exercise, and 30 minutes after exercise in healthy adults aged 18 to 65 years.

The findings of this study may contribute to improving individualized exercise prescription strategies based on sex differences in pain modulation.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Exercise-induced hypoalgesia (EIH) is characterized by a transient reduction in pain sensitivity following acute physical exercise, measurable through pressure pain thresholds (PPTs). Aerobic exercise has been consistently shown to increase PPTs in healthy individuals through activation of endogenous pain inhibitory mechanisms, including opioid and non-opioid pathways.

However, the influence of biological sex on EIH remains unclear, and understanding potential differences between men and women could have important implications for exercise prescription in clinical and healthy populations.

This quasi-experimental study will include healthy male and female participants aged 18-65 years. Participants will undergo a single session of aerobic exercise on a lower-limb cycle ergometer at 70% heart rate reserve for 30 minutes.

Pressure pain thresholds will be assessed using a validated digital pressure algometer at:

  • Quadriceps muscle (local site)
  • Lateral epicondyle region (remote site)

Measurements will be performed at three time points:

  • Pre-exercise
  • Immediately post-exercise
  • 30 minutes post-exercise

The primary analysis will compare changes in pressure pain thresholds between men and women using ANCOVA models adjusting for baseline values.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Spain
    • Madrid
      • Madrid, Madrid, Spain, 28023
        • Centro Superior de Estudios Universitarios La Salle
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Healthy male and female adults
  • Age between 18 and 65 years
  • Able to perform moderate-to-vigorous aerobic exercise
  • Able to understand study procedures
  • Cleared for exercise participation using the Physical Activity Readiness Questionnaire (PAR-Q).

Exclusion Criteria:

  • Cardiovascular, respiratory, neurological, or metabolic diseases contraindicating exercise
  • Current musculoskeletal pain or injury
  • Analgesic medication use within 24 hours prior to testing
  • Vigorous exercise within 24 hours prior to testing
  • Any contraindication to aerobic exercise

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Male participants
Participants will perform a 30-minute aerobic exercise protocol on a lower-limb cycle ergometer at 70% heart rate reserve, including warm-up and cool-down periods.
Behavioral: Aerobic exercise using cycle ergometer

Participants will perform a 30-minute aerobic exercise protocol using a lower-limb cycle ergometer at 70% heart rate reserve. The protocol includes:

  • 5-minute warm-up
  • 20-minute exercise at target intensity
  • 5-minute cool-down Heart rate will be monitored continuously using a validated heart rate monitor.
Experimental: Female participants
Aerobic exercise using lower-limb cycle ergometer. Participants will perform the same aerobic exercise protocol.
Behavioral: Aerobic exercise using cycle ergometer

Participants will perform a 30-minute aerobic exercise protocol using a lower-limb cycle ergometer at 70% heart rate reserve. The protocol includes:

  • 5-minute warm-up
  • 20-minute exercise at target intensity
  • 5-minute cool-down Heart rate will be monitored continuously using a validated heart rate monitor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pressure Pain Threshold at Quadriceps
Time Frame: Pre-exercise, immediately post-exercise, and 30 minutes post-exercise
Pressure pain threshold measured using a digital pressure algometer at the quadriceps muscle.
Pre-exercise, immediately post-exercise, and 30 minutes post-exercise

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pressure Pain Threshold at Lateral Epicondyle
Time Frame: Pre-exercise, immediately post-exercise, and 30 minutes post-exercise
Pressure pain threshold measured at a remote anatomical site using pressure algometry.
Pre-exercise, immediately post-exercise, and 30 minutes post-exercise

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centro Universitario La Salle

Collaborators

Universidad Rey Juan Carlos

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Awali, A., Nevsimal, R., O'Melia, S., Alsouhibani, A., & Bement, M. Hoeger. (2019). (305) The Contribution of Experimental Pain to the Sex Differences in Exercise-Induced Hypoalgesia. The Journal of Pain, 20(4, Supplement), S50. https://doi.org/10.1016/j.jpain.2019.01.462 Belavy, Daniel L., Oosterwijck, Jessica Van, Clarkson, Matthew, Dhondt, Evy, Mundell, Niamh L., Miller, Clint T., & Owen, Patrick J. (2021). Pain sensitivity is reduced by exercise training: Evidence from a systematic review and meta-analysis. Neuroscience & Biobehavioral Reviews, 120, 100-108. https://doi.org/10.1016/J.NEUBIOREV.2020.11.012 Cano-Climent, Antoni, Oliver-Roig, Antonio, Cabrero-García, Julio, Vries, Jolanda de, & Richart-Martínez, Miguel. (2017). The Spanish version of the Fatigue Assessment Scale: Reliability and validity assessment in postpartum women. PeerJ, 5(9). https://doi.org/10.7717/PEERJ.3832 Castañeda, Francisco Javier Rubio, Aznar, Concepción Tomás, & Baquero, Carmen Muro. (2017). Validity, Reliability and Associated Factors of the International Physical Activity Questionnaire Adapted to Elderly (IPAQ-E). Revista Espanola de Salud Publica, 91. Chesterton, Linda S., Sim, Julius, Wright, Christine C., & Foster, Nadine E. (2007). Interrater Reliability of Algometry in Measuring Pressure Pain Thresholds in Healthy Humans, Using Multiple Raters. The Clinical Journal of Pain, 23(9), 760-766. https://doi.org/10.1097/AJP.0b013e318154b6ae Day, M. L., McGuigan, M. R., Brice, G., & Foster, C. (2004). Monitoring exercise intensity during resistance training using the session RPE scale. Journal of Strength and Conditioning Research, 18(2), 353-358. https://doi.org/10.1519/R-13113.1 Faul, Franz, Erdfelder, Edgar, Lang, Albert-Georg, & Buchner, Axel. (2007). G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods, 39(2), 175-191. https://doi.org/10.3758/BF03193146 Kinser, Ann M., Sands, William A., & Stone, M

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 15, 2026

Primary Completion (Estimated)

May 15, 2026

Study Completion (Estimated)

July 15, 2026

Study Registration Dates

First Submitted

February 17, 2026

First Submitted That Met QC Criteria

February 17, 2026

First Posted (Actual)

February 23, 2026

Study Record Updates

Last Update Posted (Actual)

March 18, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • CSEULS-PI-002/2026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data regarding the principal and secondary outcomes: Pressure Pain Thresholds for the quadriceps and epicondyle sites.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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