Exercise-induced Hypoalgesia After Comparative Forms of Exercise
Condition: Pain
Study type: Interventional

Summary: 
      The study involves recording response to discomfort following different forms of exercise. We
      think that there will be a increased pain tolerance following exercise but are unsure if
      there will be a difference between exercises.
    

Detailed description: 
      Known changes of the hypothalamic-pituitary-adrenal (HPA) axis, as well as other
      neurotransmitter systems, lead to alteration of peripheral and central nociception during
      acute and chronic stress. Exercise is one example of such physiologic stress. Exercise, in
      various forms, has been shown to exert effects on pain attenuation. Several studies have
      demonstrated post-exercise reduction in pain ratings, increased pain threshold as well as
      attenuation of pain-related increases in motor evoked potentials. This phenomenon is referred
      to as exercise-induced analgesia (EIA) or, perhaps more accurately, exercise-induced
      hypoalgesia (EIH).

      Exercise at higher intensities and longer durations have the most robust evidence supporting
      their role in EIH. This is true of both long-duration aerobic training as well as
      high-intensity anaerobic training. This type of activity, however, may not be the most
      practical type of activity prescribed in a clinical population, especially in people with
      painful conditions, due to decreased conditioning and tolerance. Beyond long-duration and/or
      high-intensity aerobic exercise, there is growing evidence supporting the use of other forms
      and intensities of exercise that may induce EIH. Alternative forms of exercise, such as
      isometric stabilization, have been shown to decrease pain in a population of patients with
      low back pain. Koltyn and Arbogast investigated acute effects of exercise on pain perception
      and found that a single bout of resistance exercise at 75% of maximum intensity produces
      significant increases in pain thresholds and reductions in pain ratings.11 EIH can also occur
      during and following short duration (e.g., 1.5-5 min) and lower intensity (e.g., 15-50% max)
      isometric exercise. Along with high-intensity training, long-duration/low-intensity isometric
      contractions also have been found to produce an analgesic response. Studies have suggested
      different post-exercise pain responses in chronic pain populations compared to healthy
      controls, however questions still remain over the influence of various exercise intensities,
      protocols or types of contractions. Slater, et al examined the effects of eccentric exercise
      versus combined concentric-eccentric exercise at an intensity of 30% of max voluntary
      contraction (MVC) showed a significant increase in pain thresholds for both exercise
      protocols. Their study highlighted the need for further research to examine if changes also
      occur in response to single exercise modes. To date, no studies have compared EIH produced by
      isometric and concentric exercises at similar intensities and duration. Furthermore, little
      research in EIH has compared various forms of exercise to non-exercising controls.

      Similar to EIH induced by aerobic exercise, the relationship of anaerobic exercise with
      hypoalgesia indicates a common mechanism that may be related to the augmentation of the
      central and peripheral nervous system through modulation of descending inhibition as well as
      the release of pain-relieving substances. There is possibly an orchestra of overlying and
      inter-related physiologic, social and psychologic mechanisms that contribute to hypoalgesia
      response to exercise. Because of confounding effect of various processes of all of these
      possible processes, it is important to evaluate specific exercise regimens that may provide
      most pain relief within the context of clinical practice. Although there is good evidence
      that long-duration aerobic, and high-intensity exercises modulate pain, these strategies may
      be difficult to apply in a clinical setting due to the disabling nature of painful
      conditions. Patients with such conditions may be more apt to comply with shorter duration
      exercises at lesser intensity. No studies to date have specifically addressed differences in
      pain response when comparing the EIH following anaerobic exercises using concentric and
      isometric training bouts as well as to a non-exercising control condition. Investigation of
      EIH in this study will improve understanding of nociceptive changes following therapeutic
      exercises in a clinical setting.

      Aim 1: To examine changes in pain following two different types of exercise (isometric versus
      concentric contractions).

      Hypothesis 1a: Pain will be significantly lower following both types of exercise in
      comparison to the non-exercising control condition. Currently, it is unclear whether pain
      responses will differ between the two exercise conditions since no previous research has been
      conducted in this area.

      Aim 2: To examine whether men and women differ in pain responses following each exercise
      type.

      Hypothesis 2: There will be no sex differences in the EIH responses.

      We propose testing for EIH in healthy subjects by measuring potential differences in pressure
      pain intensity ratings with isometric versus concentric contractions as well as a control
      condition. This study seeks to determine if each of the two exercises produce EIH to same
      extent or are there differences in hypoalgesic response.

      Primary outcomes: Pain intensity ratings: Subjects will rate pain intensity using a 0 (no
      pain) to 100 (most intense pain imaginable) pain rating scale before and after application of
      a validated pressure stimulator immediately prior to, and after exercise.

      Secondary outcomes: Pain thresholds: Subjects will press a button attached to a timer out of
      view of the subject when the pressure stimulus first becomes painful. This will utilize a
      protocol recognized as a validated measurement of pain threshold.

      We aim to examine the effect of exercise-induced hypoalgesia in healthy subjects. We will
      utilize a three-treatment randomized design where all subjects will undergo two exercise
      protocols as well as a control protocol on different dates. In order to essentially eliminate
      carry-over effect, we have elected to use a washout period of >48h to ensure adequate time
      for relief of any muscle pain or fatigue.

      Subjects will first be tested for their one repetition voluntary maximum contraction (MVC)
      for the type of exercise being tested that day. Subjects will then be allowed to rest for
      10-15 minutes while we review with them the exercise protocol and have them fill out
      questionnaires including demographics, State-Trait Anxiety Inventory and Pain Catastrophizing
      Scale. Immediately prior to exercise testing, we will record baseline pulse rate and blood
      pressure readings. Pain ratings and thresholds for pressure stimuli, as described below, will
      then be measured.

      Subjects will then begin the exercise trial. Testing will be randomized so that subjects will
      perform protocols of either; a non-exercising control, concentric exercise or isometric
      exercise testing using all possible treatment sequences. Stratification for random sampling
      will be done using a block randomization scheme. For concentric testing, subjects will
      perform 5 sets of 20 reps at 30% MVC. When undergoing isometric exercise, subjects will
      perform 5 sets of sustained muscle contraction using the same duration of time it took to
      complete one set of 20 reps (as determined in pilot studies prior to initiation of this
      study). There will be a one-minute rest period between sets. Concentric testing will utilize
      a dumbbell with elbow flexion exercise. Isometric testing will be performed using a hand-grip
      dynamometer. Each exercise will be performed with the dominant arm/hand. Following exercise,
      subjects will also rate their perceived exertion and perceived muscle pain using the Borg
      Scale and Cook Scale, respectively. These are widely accepted and validated measures of
      perceived exertion and muscle pain. The control condition will consist of quiet rest for the
      same duration as the exercise conditions. At the end of the session, subjects will fill out
      two questionnaires: the State-Trait Anxiety Inventory and Situational Catastrophizing Scale.
      The validated questionnaires chosen to be completed at intake and post-testing will help to
      identify any confounding emotional or behavioral traits that may influence pain threshold and
      ratings.

      Pain testing will be conducted using a Forgioni-Barber pressure-pain stimulator to deliver
      3000-gm force to the middle digit of the non-dominant middle finger for up to 120 seconds.
      During stimulation, subjects will press a button attached to a timer when the pressure
      stimulus first becomes painful (pain threshold) and will also rate their perceived pain
      intensity using a 0-100 numeric pain rating scale at 20 second intervals during the 2 minute
      exposure to the pressure stimulus. This validated protocol has been used in previous research
      by investigators in this study.

      Risks:

      Subjects will insert the middle forefinger into the chute of the Forgioni-Barber pain
      stimulator where a non-fixed Lucite edge will contact the finger with a constant application
      of pressure from a 3 kg weight. This device creates a stimulus that is easy to apply and
      produces a distinct pain sensation with rapid onset and offset. It produces no tissue damage
      or psychological or physical health risk, and the subject is able to stop the stimulus at any
      time. The pain intensity is repeatable and readily discriminable throughout the stimulus
      application. Previous research has demonstrated that the Forgioni-Barber pressure-pain
      stimulator device, using the described procedure, is a safe device that produces a painful
      stimulus but does not cause tissue damage or injury. No significant adverse or side effects
      have been experienced or are expected from the exercise or pain stimulus. Temporary
      discomfort is expected during application of the pain stimulus, however this should resolve
      upon removal of the stimulus. There are no permanent consequences expected of this testing
      procedure. If the subject experiences excessive discomfort at any time during pain testing,
      we will immediately remove the stimulus. The subjects may withdraw from testing at any time
      during the research.

      With exercise, there is a slight risk of muscle soreness or strain. We will mitigate risk of
      muscle strain by instructing the subjects to stop the exercise if they feel they are
      over-straining or begin to feel discomfort when performing the activity. The investigators
      will also be immediately available to assist, if needed, if the subject experiences
      discomfort during the exercise session. It is well known that repetitive contractions have a
      possibility of inducing delayed onset muscle soreness (DOMS). This is known to occur most
      often with eccentric exercises. Previous research has shown that there was no effect from
      DOMS using the intended protocol described and that a washout period of 24 hours was adequate
      with eccentric loading.

      32 healthy normotensive males and females in the age range 18 to 40 years will be recruited
      from the community.
    

Intervention name(s): Forgionei-Barber pressure-pain stimulator; Concentric Exercise; isometric exercise
Intervention type(s): Device; Other; Other
Intervention description(s): Pain testing will be conducted using a Forgioni-Barber pressure-pain stimulator to deliver 3000-gm force to the middle digit of the non-dominant middle finger for up to 120 seconds. During stimulation, subjects will press a button attached to a timer when the pressure stimulus first becomes painful (pain threshold) and will also rate their perceived pain intensity using a 0-100 numeric pain rating scale at 20 second intervals during the 2 minute exposure to the pressure stimulus. This validated protocol has been used in previous research by investigators in this study. This will be used for both exercise sessions and the control session. Forgionei-Barber pressure-pain stimulator will be used.; Concentric testing will utilize a dumbbell with elbow flexion exercise. Subjects will perform 5 sets of 20 reps at 30% MVC. Pain testing will be conducted using a Forgionei-Barber pressure-pain stimulator immediately before and after the exercise.; When undergoing isometric exercise, subjects will perform 5 sets of sustained muscle contraction for 65 seconds using a hand-grip dynamometer. Pain testing will be conducted using a Forgionei-Barber pressure-pain stimulator immediately before and after the exercise.
Intervention model: Single Group Assignment
Intervention model description: three treatment design, all participants will perform two exercise sessions (isometric exercise, concentric exercise), as well as a control session in a randomized manner. (This is not a cross-over design as each participant will have their own randomized order of sessions of exercise & control sessions.)
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pain; exercise-induced hypoalgesia