NCT07083219

Brief Summary

Exercise-Induced Hypoalgesia (EIH) refers to reduced pain sensitivity following exercise, particularly in response to noxious stimuli. Various exercise modalities, including isometric, aerobic, and resistance training, contribute to this effect. Pain experienced during exercise may activate descending inhibitory pathways, leading to subsequent pain relief. Conditioned Pain Modulation (CPM) is a behavioral measure of diffuse noxious inhibitory control (DNIC), where pain inhibits pain. It is proposed that pain within the exercising limb may serve as a conditioning stimulus, activating CPM. For instance, maximal handgrip exercise has been used to trigger CPM responses. In clinical settings, unpleasant physical therapy interventions like exercise, thermal modalities, and electrical stimulation may function through CPM mechanisms. CPM predicts EIH in both young and older adults, with painful exercise reducing pressure pain ratings across age groups. Isometric exercise has also been shown to decrease CPM in individuals with systemic EIH, suggesting shared mechanisms. Athletes exhibit higher pain thresholds and tolerance due to repeated exposure to high-intensity exercise. However, they demonstrate lower CPM activation, possibly as a compensatory response to chronic noxious input. This raises the question: Can repeated high-intensity aerobic exercise, perceived as painful, train the nervous system to enhance descending pain inhibition in non-athletes? While alterations in pain sensitivity related to analgesic-induced pain inhibition have been documented, the effects of continuous stimulation of central pain pathways via painful high intensity exercise, along with the mediating influence of psychosocial factors, remain underexplored. This study aims to investigate the central pain modulatory mechanisms (measured by QST) that have differential changes in participants who receive multiple sessions of high intensity aerobic exercise as an intervention compared to receiving single session. Additionally, the study will evaluate the impact of sociocultural factors, including optimism, pain catastrophizing, and marginalization on alterations in pain sensitivity.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
7mo left

Started Aug 2025

Geographic Reach
1 country

1 active site

Status
enrolling by invitation

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress56%
Aug 2025Dec 2026

First Submitted

Initial submission to the registry

June 3, 2025

Completed
2 months until next milestone

First Posted

Study publicly available on registry

July 24, 2025

Completed
22 days until next milestone

Study Start

First participant enrolled

August 15, 2025

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2026

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2026

Last Updated

December 10, 2025

Status Verified

December 1, 2025

Enrollment Period

11 months

First QC Date

June 3, 2025

Last Update Submit

December 3, 2025

Conditions

Keywords

PainConditioned Pain ModulationAerobic Exercise

Outcome Measures

Primary Outcomes (10)

  • Static QST Measure

    Slow Ramp: A slowly ramping thermal stimulus will be delivered to the skin of the participant's dominant forearm using a computer controlled TSAII NeuroSensory Analyzer from Medoc, Inc. Thermal stimuli will increase from a baseline of 35 degrees Celsius to a maximum of 51 degree Celsius in ascending one-degree intervals, each stimulus presented for 1-sec. Participants will be instructed to indicate when the sensation first changes from warmth to pain (pain threshold) and when the sensation becomes "so painful you can no longer tolerate it or So painful that you can't bear it anymore" (pain tolerance). Pressure Pain Threshold: An algometer with a 1 cm diameter rubber tip will be applied at 1 kg/s to the dominant hand at the first dorsal interosseous muscle. Participants will be instructed to indicate when the sensation first changes from pressure to pain (pain threshold). This procedure will be repeated two times, and the average pressure to threshold will be analyzed.

    2 weeks

  • Dynamic QST Measure

    Pressure pain threshold will be measured using a 1 cm² algometer tip applied at 1 kg/s to the dominant foot's web space. Pressure increases until participants report pain at 40/100, then stops. This is repeated twice, and the average is used. For the conditioning stimulus, participants immerse their non-dominant hand in circulating cold water (6°C for males, 8°C for females) for 60 seconds, across four trials. Pain and unpleasantness ratings are collected each trial. Water temperature is adjusted in subsequent trials if ratings are too high or low. Between immersions, the hand is removed for 30 seconds while PPT is reassessed. Conditioned pain modulation is calculated as the difference between post-conditioning and pre-conditioning pain thresholds, with negative values indicating efficient pain inhibition.

    2 weeks

  • Temporal Summation

    Temporal sensory summation (TSS): 6 heat pulses will be applied to the dominant hand of the patient. To ensure temporal summation, an inter-stimulus interval of 2 seconds will be used with temperatures starting at 39°C and increasing to 50°C (the TSA medoc maintains 10°C/sec rate in this range which is sufficient for maintaining the desired inter-stimulus interval). The participants will be asked to rate the magnitude of their delayed (second) pain sensation following each heat pulse using the numeric rating scale. These response ratings are believed to be primarily C-fiber mediated. The magnitude of TSS is calculated by subtracting the rating of intensity at pulse 1 from the peak rating given during the 6 pulses (ie simple slope of summation).

    2 weeks

  • Aftersenstations

    The participants will be asked to rate the magnitude of their pain sensation following the removal of the thermode. The research assistant will cue the participants to rate their pain every 10 seconds. These ratings will be obtained for 60 seconds. These response ratings are also primarily C-fiber mediated.

    2 weeks

  • Pressure Pain Threshold Upper Extrimity

    An algometer with a 1 cm diameter rubber tip will be applied at 1 kg/s to the dominant hand at the first dorsal interosseous muscle. Participants will be instructed to indicate when the sensation first changes from pressure to pain (pain threshold). This procedure will be repeated two times, and the average pressure to threshold will be analyzed.

    2 weeks

  • Life Orientation Test-Revised (LOT-R)

    The LOT-R is a 10-item self-report scale that measures how optimistic or pessimistic a person feels about the future. It measures trait optimism. The LOT-R uses a 5-point Likert scale, with 0 meaning "strongly disagree" and 4 meaning "strongly agree". Items are summed, yielding a range from 0 to 32 and Higher scores indicate greater levels of optimism

    2 weeks

  • State Optimism Measure (SOM)

    The SOM is a 7-item measure that measures a person's state of optimism. It scored from 1 to 7 and higher scores indicate with a higher score indicating greater state optimism. It has been shown to be reliable and valid in both general and clinical populations

    2 weeks

  • The Perceived Societal Marginalization (PSM)

    The PSM scale is a tool that measures how people perceive their social group's lack of recognition and insignificance in the areas of culture, politics, and the economy. The scale's items are scored on a 6-point Likert scale, with 1 representing "strongly disagree" and 6 representing "strongly agree". A higher total score indicates a higher level of perceived societal marginalization

    2 weeks

  • Anxiety about Pain Testing

    A single item visual analogue scale (VAS) for Anxiety about Pain Testing was administered before every session of the protocol. The VAS was 100mm long and participants were instructed that the anchors were "no anxiety about pain testing" on the left and "worst anxiety about pain testing imaginable" on the right.

    2 weeks

  • Pain Catastrophizing Scale (PCS)

    The Pain Catastrophizing Scale is a 13-item questionnaire in which individuals respond to a statement on a five-point ordinal scale from 0 to 4. Individuals respond to the question in terms of a prior painful episode, and higher scores indicate higher pain catastrophizing levels

    2 weeks

Study Arms (3)

Multiple Exercise Session Group (MES)

EXPERIMENTAL

Participants will undergo six sessions, including four sessions of aerobic exercise intervention with QST assessed during each session and questionnaires completed during the first and fifth sessions. Participants will attend six sessions over two weeks (approximately every 48-72 hours).

Behavioral: Aerobic High Intensity Interval Training

Single Exercise Session Group (SES)

ACTIVE COMPARATOR

Participants will undergo three sessions, including one aerobic exercise intervention session with QST, and questionnaires assessed during both sessions. Participants will attend three sessions, with the second session approximately two weeks after the first. Each visit will last between 1 to 1.5 hours.

Behavioral: Aerobic High Intensity Interval Training

No Exercise Session (NES)

NO INTERVENTION

Participants will undergo two sessions without any exercise intervention, with QST assessed and questionnaires completed during both sessions.

Interventions

HIIT Protocol (Individualization of Exercise Program): Peak power will be calculated with Graded Exercise Test (GXT), with 90% of peak power used as the target range for the intervention. Total Training Time: 35 minutes. Warm-Up Phase: 1. Duration: 10 minutes 2. Intensity: 40-50% of peak power HIIT Work and Rest Cycles: Each session includes 20 minutes of intervals with the following pattern: Work: 1 minute at 90% of peak power Rest: 3 minutes at 40% of peak power Repeat for five cycles. 5 minute cool down at 40% of peak power Monitoring: VO₂ and heart rate will be continuously measured. Lactate levels will be measured at the following points: 1. Before the warm-up 2. After completing the warm-up (1st-minute intervention) 3. During the second minute of each rest period

Multiple Exercise Session Group (MES)Single Exercise Session Group (SES)

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • pain-free
  • between 18-50 years old.

You may not qualify if:

  • Participants will not be excluded based on race or gender but will be excluded if they meet any of the following
  • non-English speaking
  • systemic medical condition is known to affect sensation
  • regular use of prescription pain medication to manage pain
  • current or history of chronic pain condition
  • currently using blood thinning medication
  • any blood clotting disorder such as hemophilia
  • any contraindication to the application of ice or cold packs, such as uncontrolled hypertension, cold urticaria, cryoglobulinemia, paroxysmal cold hemoglobinuria, and circulatory compromise
  • involved in vigorous physical activities like heavy lifting, digging, aerobics or fast bicycling
  • Any lung or respiratory condition that impairs exercise capacity, including but not limited to asthma.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Physical Therapy and Movement Science, University of Texas at El Paso

El Paso, Texas, 79902, United States

Location

Related Publications (2)

  • Brown SD, Unger Hu KA, Mevi AA, Hedderson MM, Shan J, Quesenberry CP, Ferrara A. The multigroup ethnic identity measure-revised: measurement invariance across racial and ethnic groups. J Couns Psychol. 2014 Jan;61(1):154-161. doi: 10.1037/a0034749. Epub 2013 Nov 4.

  • Bollwerk, M., Wetzel, E., Schlipphak, B., & Back, M. D. (2024). Who feels marginalized? A latent class analysis of perceived societal marginalization. Group Processes and Intergroup Relations, 27(3), 597-618. https://doi.org/10.1177/13684302231182924

    RESULT

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Priyanka Rana, PT, MPT, PhD

    Department of Physical Therapy and Movement Science, University of Texas at El Paso

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

June 3, 2025

First Posted

July 24, 2025

Study Start

August 15, 2025

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

December 1, 2026

Last Updated

December 10, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Locations