Exercise and Pain Sensitivity

• Change in muscle strength [ Time Frame: baseline and after 12 weeks ] [ Designated as safety issue: No ]
  Muscle strength is measured in knee extension and flexion and in arm extension and flexion (bench press and pull)
• Change in cardiovascular fitness [ Time Frame: baseline after 4 weeks and after 12 weeks ] [ Designated as safety issue: No ]
  Watt max test is performed on a bicycle ergometer to estimate the maximal oxygen uptake velocity
• Change in baroreflex sensitivity [ Time Frame: baseline after 4 weeks and after 12 weeks ] [ Designated as safety issue: No ]
  Heart rate and blood pressure variability is measured during rest and during quiet standing.

• Change in pressure pain thresholds [ Time Frame: Baseline, after 4 weeks and afte 12 weeks ] [ Designated as safety issue: No ]
  The pressure pain threshold is measured by computer controlled pressure algometry. Pressure pain thresholds are evaluated at the knee, on the quadriceps muscle, on the sacral bone, on the erector spinae muscle, on the coracoid proces and on the deltoid muscle.
• Change in pain intensity during experimental muscle pain [ Time Frame: baseline, after 4 weeks and 12 weeks ] [ Designated as safety issue: No ]
  Experimental muscle pain is induced by injection of 1 ml hypertonic saline (5.8%) into the Vasus lateralis and the deltoid msucels. The outcome is the maximal pain intensity during the experimental pain measured on 100 mm visual analogue scale.
• Change in muscle strength [ Time Frame: baseline, after 4 weeks and after 12 weeks ] [ Designated as safety issue: No ]
  Muscle strength is measured in knee extension and flexion and in arm extension and flexion (bench press and pull)
• Change in cardiovascular fitness [ Time Frame: baseline after 4 weeks and after 12 weeks ] [ Designated as safety issue: No ]
  Watt max test is performed on a bicycle ergometer to estimate the maximal oxygen uptake velocity
• Change in baroreflex sensitivity [ Time Frame: baseline after 4 weeks and after 12 weeks ] [ Designated as safety issue: No ]
  Heart rate and blood pressure variability is measured during rest and during quiet standing.

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.

• Other: Knee muscle strengthening exercises
  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
• Other: Upper extremity strengthening exercises
  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
• Other: Cardiovascular fitness exercises
  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

• No Intervention: Control
  No intervention for 12 weeks
• Active Comparator: Knee muscle strengthening exercises
  Intervention: Other: Knee muscle strengthening exercises
• Active Comparator: Upper extremity strengthening exercises
  Intervention: Other: Upper extremity strengthening exercises
• Active Comparator: Cardiovascular fitness exercises
  Intervention: Other: Cardiovascular fitness exercises

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