The study was terminated prematurely due to difficulties in participant recruitment. We reframed the project as a pilot feasibility study to better assess recruitment processes and inform the design of a future full-scale trial.

Previous studies have shown that healthy individuals who take more steps per day and who spend more time on moderate- to vigorous-intensity activities exhibit better pain inhibition and less pain facilitation. Furthermore, exercise training (i.e., exercise performed over a number of sessions) can result in reduced pain sensitivity (increased pressure pain threshold). However, the optimal exercise prescription required to achieve pain sensitivity reduction is currently unclear. The next step is to determine experimentally whether increasing physical fitness will lead to positive effects on central pain processing (i.e., pain sensitivity, pain modulation, spinal nociception). The aim of this study is to examine the effects of two exercise programs on central pain processing in healthy sedentary individuals. In case of positive effects, this would provide a rationale for the future to investigate this in chronic pain patients with impaired pain modulation.

Objectives:

Since research on the effects of chronic exercise interventions on pain modulation is scarce and since there is no optimal exercise prescription to reduce pain sensitivity, the effects of a moderate intensity training (MIT) program versus a high intensity training (HIT) program on central pain processing will be examined in healthy sedentary individuals.

Study population:

Thirty healthy sedentary adults between 18 and 55 years of age and with a body mass index (BMI) between 20 and 25 kg/cm² will be recruited. Sedentary is defined as "having a sedentary job and performing less than three hours of moderate physical activity per week". Moderate physical activity is defined as "an activity that requires at least three times the amount of passively expended energy". The sample size was calculated based on a similar previously conducted study.

Study Protocol:

The participants will be invited for a first contact moment (T0) at Ghent University Hospital or at the participant's homes. During T0, participants will be asked to sign an informed consent form. Furthermore, the procedure of the intervention will be explained and a general questionnaire on sociodemographic and health-related characteristics will be administered. Participants will then receive an ActiGraph accelerometer to take home and wear for seven consecutive days to monitor physical activity (i.e., number of steps, moderate and vigorous physical activity, and sedentary behavior).

After wearing the Actigraph accelerometer for seven consecutive days, participants will be invited for a first test moment (T1) at Ghent University Hospital. During T1, three questionnaires will be administered, namely a day survey (intake of medication, caffeine, alcohol and nicotine in the past 24 hours and performance of extreme physical exertion in the past 48 hours), the International Physical Activity Questionnaire (IPAQ) and the Hospital Anxiety and Depression Scale (HADS). Before the start of the experimental pain measurements, blood pressure will be measured with a blood pressure monitor and resting heart rate will be measured using a heart rate belt around the chest.

Next, central pain processing will be assessed:

1. to evaluate pain sensitivity, pressure algometry will be performed using a digital algometer to determine the pressure pain threshold (PPT) bilaterally on the muscle belly of the extensor carpi radialis and the rectus femoris.
2. to evaluate pain inhibition, a conditioned pain modulation (CPM) paradigm will be performed in which the measurement of the PPT (= test stimulus (TS)) will be repeated on the dominant body side during (at minute two) and two minutes after immersion of the non-dominant hand in a warm water bath (= conditioning stimulus (CS)) of 45.5°C for six minutes.
3. to evaluate exercise-induced hypoalgesia (EIH), the PPT measurements will be repeated before (bilaterally) and after (on the dominant body side) a submaximal exercise test (Aerobic Power Index test) performed on an electrically braked bicycle ergometer. Cycling will start at a load of 25 W. Then the load will be increased by 25 W every minute until the submaximal level, defined as 75% of the predicted maximum heart rate (= 220 - age), is reached. Heart rate will be measured before, during, and after the test with a heart rate belt around the chest.
4. to evaluate spinal nociception, transcutaneous electrical neurostimulation (TENS) of the n. suralis of the dominant leg will be performed using a bar electrode. The nociceptive flexion reflex (NFR) threshold will be determined, as well as the pain intensity during repetitive stimulation at the intensity of the NFR threshold to evaluate temporal summation of the NFR. The elicitation of the NFR will be evaluated by measuring the involuntary contraction of the ipsilateral biceps femoris, which will be recorded using electromyography (EMG).

After the experimental pain measurements, the test subjects will receive a Fitbit smartwatch to measure weekly step count during the 10-week exercise program.

After T1, the participants will be randomly assigned to one of two 10-week intervention programs, namely a MIT or a HIT program based on a 1:1 ratio.

Upon completion of the intervention, participants' physical activity will be monitored again for 7 consecutive days using an Actigraph accelerometer. After these 7 days, participants will be invited again for a second test moment (T2) at Ghent University Hospital. During T2, the day survey and the IPAQ will be administered again, blood pressure will be measured and the pain measurements will be repeated.

Inclusion Criteria:

• age between 18 and 55 years
• BMI between 20 and 25 kg/m²
• Dutch-speaking
• sedentary job and performing less than 3 hours of moderate physical activity per week

Exclusion Criteria:

• current pain complaints or other (medical and/or psychological) health problems
• history of serious pain complaints or (medical and/or psychological) health problems
• history of serious conditions (e.g. cancer, cardiovascular disease, epilepsy, diabetes, depression, etc.)
• being pregnant
• pregnant in the past 12 months
• currently breastfeeding