NCT07105410

Brief Summary

Further research is needed to explore the analgesic effects of post-acute and chronic exercise and if effects are partially dependent on lower H-reflex/V-wave inhibition by group III and IV muscle afferents desensitization. In addition, it is important to note that the available research examining the interaction between exercise (acute and chronic) and pain did not compare the effect of different exercise modalities. Moreover, since discharge rate of III and IV afferents is highly dependent on specific task-metabolic requirements, it is relevant to determine if exercise modality differentially modulates the possible analgesic response via metaboreflex desensitization. Therefore, with this project, the investigators aim at exploring the influence of experimentally induced metaboreflex activation (group III and IV afferents) (maintained submaximal isometric contraction followed by blood-flow occlusion - post-exercise circulatory occlusion (PECO)) Vs. a control condition (no isometric contraction nor blood flow occlusion), on H-reflex recruitment curve and V-wave excitability (aim #1). Since the activation of group III/IV afferents can inhibit the corticospinal pathway, the investigators hypothesize that the normalized maximal amplitude of H- and V-wave and the slope of the ascending limb of the H-recruitment curve will decrease with metaboreflex activation (during PECO). Additionally, the investigators intend to examine the acute impact of different lower-limb exercise regimens (aerobic, anaerobic and dynamic resistance) on pain sensitivity (by the application of a foot cold pain tolerance test, by determining pressure pain threshold of exercising and non-exercising muscles and through self-reported leg ischemic pain ratings (0-10 Cook scale) - during PECO) (aim #2). Participants are also asked to mark the intensity of cold pain sensation using a visual analogue scale (VAS) with a horizontal line of 100mm, every 30 s of testing.This will allow the investigators to investigate the analgesic role of different acute exercise paradigms through possible metaboreflex desensitization given by altered neuromuscular responses at post-exercise time point (attenuated inhibition of H-reflex and V-wave amplitude during PECO). Also, once past research has shown that muscle metaboreflex activation reduces the sensitivity of the baroreflex, the investigators will measure arterial pressure (AP) and heart rate variability (HRV) during cold test and AP during ischemic testing. Despite all exercise modalities could enhance reducing pain sensibility after exercise, the investigators hypothesize that resistance and anaerobic exercise stimuli will enhance pain threshold/tolerance and reduced pain ratings via metaboreflex desensitization compared to that seen with endurance exercise (attenuated increase of AP and sympathetic component of HRV during cold pressor test and attenuated increase of AP during ischemic pain test). Finally, the investigators intend to explore the impact of long-term aerobic, anaerobic and resistance training on pain sensibility, using the same tests of aim #2 (aim #3). The investigators hypothesize that chronic EIH will be of greater magnitude after anaerobic and resistance exercise training vs. endurance training. This will be related with attenuated inhibition of H-reflex and V-wave amplitude measured during PECO and attenuated increase of AP and sympathetic component of HRV during metaboreflex activation after those training modalities. Nevertheless, the investigators expect to see an increased motor performance in all training regimens via heightened H-reflex (aerobic and anaerobic groups) and V-wave (resistance group) excitability.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
48

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2022

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

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 Start

First participant enrolled

January 1, 2022

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2022

Completed
2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2025

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

July 17, 2025

Completed
19 days until next milestone

First Posted

Study publicly available on registry

August 5, 2025

Completed
Last Updated

August 5, 2025

Status Verified

July 1, 2025

Enrollment Period

12 months

First QC Date

July 17, 2025

Last Update Submit

July 29, 2025

Conditions

Keywords

hypoalgesiapain

Outcome Measures

Primary Outcomes (14)

  • H-reflex

    With soleus electromyographic recording electrode (Delsys) and electrical stimulation of the tibial nerve (Stimsola) the H-reflex recruitment curve parameters (spinal excitability) will be obtained in a 4-min protocol

    During PECO and No-PECO conditions (aim #1); Pre-post acute exercise during PECO (aim #2); Pre-post 6 weeks of training during PECO (aim #3)

  • V-wave

    With soleus electromyographic recording electrode (Delsys) and electrical stimulation of the tibial nerve (Stimsola) the V-wave parameters (spinal and supraspinal excitability) will be obtained

    During PECO and No-PECO conditions (aim #1); Pre-post acute exercise during PECO (aim #2); Pre-post 6 weeks of training during PECO (aim #3)

  • Ischemic pain ratings

    Participants will be asked to rate their leg pain intensity twice at the 4-min H-reflex protocol (at 2nd and 4th min of the procedure) using a Cook pain sale (0-10). In the scale, 0 represents no pain while 10 represents the worst possible pain

    During PECO and No-PECO conditions (aim #1); Pre-post acute exercise during PECO (aim #2); Pre-post 6 weeks of training during PECO (aim #3)

  • Arterial blood pressure

    Brachial arterial pressure will be measured twice at the 4-min H-reflex protocol (at 2nd and 4th min of the procedure) by an automated equiment (Tango SunTech Medical)

    During PECO and No-PECO conditions (aim #1); Pre-post acute exercise during PECO (aim #2); Pre-post 6 weeks of training during PECO (aim #3)

  • Pressure pain threshold

    It will be assessed with an analogue algometer (FDK 60, Wagner Instruments) (in rectus femoris, upper-trapezius and biceps brachiis muscles). It measures the kg of force at the time participants report they are feeling pain intead of pressure

    Pre-post acute exercise (aim #2); Pre-post 6 weeks of training (aim #3)

  • Cold pain tolerance

    It will be assessed with participants immersing their right foot into a container with cold water between 0 and 2ºC. It measures the time participants can endure the cold painful stimuli

    Pre-post acute exercise (aim #2); Pre-post 6 weeks of training (aim #3)

  • Cold pain ratings

    While participants immerse their right foot into a container with cold water between 0 and 2ºC, they will beasked to rate the intensity of pain they perceived each minute by writing in a visual analogue scale (0-100mm) that pain intensity. 0 is considered no-pain and 100 the worst possible pain

    Pre-post acute exercise (aim #2); Pre-post 6 weeks of training (aim #3)

  • Heart rate variability during cold pain testing

    It will be measured continuosly during the time participants have their foot in cold water using a heart rate monitor (Polar H10)

    Pre-post acute exercise (aim #2); Pre-post 6 weeks of training (aim #3)

  • Arterial blood pressure during cold pain testing

    It will be measured each minute during the time participants have their foot in cold water using an automatic equipment (Tango SunTech Medical)

    Pre-post acute exercise (aim #2); Pre-post 6 weeks of training (aim #3)

  • Maximal oxygen uptake

    For the aerobic group, it will be determined in a treadmill graded exercise testing using a gas analyses system (Metamax, Cortex)

    Pre-post 6 weeks of training (aim #3)

  • Peak power

    For the anaerobic group, it will be determined with a 30-s Wingate all-out test (Monark cycloergometer)

    Pre-post 6 weeks of training (aim #3)

  • Maximal voluntary isometric contraction

    For the dynamic resistance group, it will be determined for the knee extensors muscles using an isokinetic dynamometer (Biodex)

    Pre-post 6 weeks of training (aim #3)

  • H-reflex after training

    With soleus electromyographic recording electrode (Delsys) and electrical stimulation of the tibial nerve (Stimsola) the H-reflex recruitment curve parameters (spinal excitability) will be obtained

    Pre-post 6 weeks of training (aim #3)

  • V-wave after training

    With soleus electromyographic recording electrode (Delsys) and electrical stimulation of the tibial nerve (Stimsola) the V-wave parameters (spinal and supraspinal excitability) will be obtained

    Pre-post 6 weeks of training (aim #3)

Study Arms (3)

PECO and No-PECO

EXPERIMENTAL
Other: Aim #1: The effect of post-exercise circulatory occlusion on H-reflex and V-wave

Aerobic, Anaerobic and Dynamic Resistance Exercise

EXPERIMENTAL
Other: Aim #2: The hypoalgesic effects of acute exercise of different modalities

Aerobic, Anaerobic, Dynamic Resistance Training and Control Group

EXPERIMENTAL
Other: Aim #3: The hypoalgesic effects of chronic training of different modalities

Interventions

Aim #1 follows a randomized and crossover design in which 16 young and healthy males are evaluated during thigh circulatory occlusion performed after a submaximal isometric plantar flexion contraction (PECO day). In the other session, participants are evaluated during free-flow conditions and without previous fatiguing contraction (no-PECO day). In PECO day, participants complete a 3-min contraction at 40% of maximal force. Then, for testing, blood flow from lower-leg is blocked during 4 min, by an inflatable cuff around the ipsilateral thigh before task termination, during which H- reflex is tested. At the end of recordings, the cuff is deflated. Participants ware allowed to rest for 5-10 min. Then, they are requested to perform a new 3 min contraction with the cuff being inflated before task termination. The cuff remains inflated for \~ 2 min during which V-wave recordings are obtained. In both days, leg pain intensity is reported by participants and brachial AP is measured.

PECO and No-PECO

Aim #2 follows a randomized and crossover-controlled design, consisting on two experimental sessions. 24 healthy male (all diferent from Experiment 1) are randomly allocated to one of the following exercising regimens: aerobic, anaerobic or dynamic resistance (8 participants for each exercise group). In one of the experimental days, participants are evaluated for pain sensitivity and neuromuscular responses both before and after a lower-limb acute exercise protocol (exercise day) and in the other day before and after 15 min of quiet rest (non-exercise day). In both sessions, participants are evaluated for rectus femoris, upper trapezius and biceps brachiis muscles pressure pain threshold, followed by the application of a cold pain tolerance test on the foot. The intensity of pain is reported by a 0-100mm VAS and AP and HRV continously measured. Then, participants are tested for H-reflex and V-wave excitability during PECO, with leg pain intensity (0-10) and brachial AP recorded.

Aerobic, Anaerobic and Dynamic Resistance Exercise

Aim #3 follows a randomized-controlled design. 32 healthy male (all the 24 participants from Experimental 2 plus 8 new subjects) are randomly allocated to one of the following groups: aerobic, anaerobic, dynamic resistance training and no-training (control) (8 participants for each group). Each intervention group perform 6 weeks of exercise training (3x week). Participants allocated to each training group are evaluated before and after training (2 assessment days in each time-point). On one day participants are tested for pressure pain threshold and cold pain tolerance with concomitant measures of pain ratings (0-100mm VAS), AP and HRV. The influence of metaboreflex activation on H-reflex and V-wave is also measured (during PECO). In addition, during PECO ischemic pain rating and AP are obtained. On another day, participants are evaluated for motor performance (maximal oxygen uptake, maximal voluntary contraction and peak power) and neuromuscular adaptations (i.e. H-reflex and V-wave)

Aerobic, Anaerobic, Dynamic Resistance Training and Control Group

Eligibility Criteria

Age18 Years - 35 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • years males
  • Healthy (health status determined from a health-screening questionnaire performed at study admission)
  • Normal arterial blood pressure (ABP) (cut-off values for systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) of ≤ 120/80 mmHg)

You may not qualify if:

  • Neurologic disease
  • Metabolic disease
  • Cardiovascular disease
  • Respiratory disease
  • Musculoskeletal issues in the 3 previous months limiting exercise performance
  • Taking any chronic medications for the treatment of pain or had any pain related condition

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Faculdade de Motricidade Humana

Lisbon, 2685-224, Portugal

Location

MeSH Terms

Conditions

Motor ActivityFatigueBites and StingsPain

Condition Hierarchy (Ancestors)

BehaviorSigns and SymptomsPathological Conditions, Signs and SymptomsPoisoningChemically-Induced DisordersWounds and InjuriesNeurologic Manifestations

Study Officials

  • Gonçalo V Mendonça, PhD

    Faculdade de Motricidade Humana

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MSc

Study Record Dates

First Submitted

July 17, 2025

First Posted

August 5, 2025

Study Start

January 1, 2022

Primary Completion

December 30, 2022

Study Completion

May 30, 2025

Last Updated

August 5, 2025

Record last verified: 2025-07

Locations