Exercise and Pain Sensitivity

Study Overview
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Brief Summary
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There is ample evidence that exercise therapy is beneficial with respect to pain in patients with osteoarthritis of the knee. However, the pain relieving mechanisms are unknown. To enhance the efficacy of exercise therapy a deeper understanding of the involved mechanisms is needed. Different exercise types may affect the pain sensitivity differently. It is hypothesized that non-specific exercises (i.e. exercises that does not involve the knee) reduces the processing of pain in the central nervous system (central sensitivity) to knee joint pain in healthy subjects. It is also hypothesized that exercises that involve the knee (i.e. specific knee exercises) reduce the sensitivity of pain receptors in the knee (peripheral sensitivity) in healthy subjects. Healthy volunteers are recruited and randomised to one of four interventions: 1: Muscle strengthening exercises involving the thigh muscles; 2: Muscle strengthening exercises involving the shoulder muscles; 3: Cardio-vascular fitness exercises; or 4: Control (no exercises). The active interventions include exercises three times per week for 12 weeks. Pain sensitivity and a range of explanatory variables is measured before the interventions, after 4 weeks and after 12 weeks.

Official Title
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Exercise and Alterations in Pain Sensitivity

Conditions
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Knee Pain

Intervention / Treatment
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* Other: Knee muscle strengthening exercises
* Other: Upper extremity strengthening exercises
* Other: Cardiovascular fitness exercises


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 35 years Untrained (i.e. less than 2 hours of organised exercise per week in the last 6 months - physical activity related to transportation (e.g. bicycling) is not included) Generally healthy according a medical exam at screening, history Willing and able to participate in all measurements Willing and able to attend all training sessions Willing to keep the habitual activity and amount of training constant (ie screening activity and training volume). 20 ≤ body mass index (BMI) ≤ 28 kg/m2 Speak, read and write Danish Exclusion Criteria: Pregnant or breastfeeding Current or previous symptoms of autoimmune disease (eg, inflammatory bowel disease, multiple sclerosis, lupus, rheumatoid arthritis) Planned surgery during the study period Current or former musculoskeletal injuries or illnesses, including but not confined to: Ligament Injuries Meniscus Injuries Osteoarthritis Patellofemoral Pain Syndrome Backache Neck pain tendinopathy Current or past diagnosis, signs or symptoms of significant cardiovascular disease, including but not limited to: Ischemic heart disease Arteriosclerosis Medical conditions that contraindicate exercise, including but not limited to: Chronic or congenital heart disease Asthma Chronic Obstructive Pulmonary Disease Past or current diagnosis, signs or symptoms of significant neurological disease, in-incl. but not limited to: Blood clot in brain Stroke Clinically significant head trauma within the last year Peripheral neuropathy Epilepsy or seizures Impaired balance Alcohol or drug abuse within the past 5 years Past or current diagnosis, signs or symptoms of major psychiatric disorder Regional pain syndromes like fibromyalgia Regional pain caused by lumbar nerve root or cervical radiculopathy with or at risk for developing it

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>No intervention for 12 weeks | |
| Active Comparator: Knee muscle strengthening exercises<br> | Other: Knee muscle strengthening exercises<br>* Muscle strengthening exercises of the quadriceps and hamstring muscles will be performed based on a standard muscle strengthening exercise paradigm: 3 sets with 6-8 repetitions (corresponding to approximately 80% repetition maximum (RM)) will be performed. The training load will be progressed by means of weekly estimates of muscle strength to ensure a constant load of 80% RM. The exercises will be supervised<br>|
| Active Comparator: Upper extremity strengthening exercises<br> | Other: Upper extremity strengthening exercises<br>* Muscle strengthening exercises of the upper amrs and shoulder girdle will be performed based on a standard muscle strengthening exercise paradigm: 3 sets with 6-8 repetitions (corresponding to approximately 80% repetition maximum (RM)) will be performed. The training load will be progressed by means of weekly estimates of muscle strength to ensure a constant load of 80% RM. The exercises will be supervised<br>|
| Active Comparator: Cardiovascular fitness exercises<br> | Other: Cardiovascular fitness exercises<br>* Cardiovascular fitness exercises encompass circuit training including exercises on (but not limited to): ergometer cycles, treadmills (running), and cross-trainers. The exercise intensity is aiming at exercises within 60-85% of maximum heart rate (defined as 220 - age). The heart rate is monitored using a standard heart rate monitor. The exercises will be supervised<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pressure pain sensitivity |  | Baseline, and after 12 weeks of exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle strength | Muscle strength is measured in knee extension and flexion and in arm extension and flexion (bench press and pull) | baseline and after 12 weeks | 
| Change in cardiovascular fitness | Watt max test is performed on a bicycle ergometer to estimate the maximal oxygen uptake velocity | baseline after 4 weeks and after 12 weeks | 
| Change in baroreflex sensitivity | Heart rate and blood pressure variability is measured during rest and during quiet standing. | baseline after 4 weeks and after 12 weeks |