Acute Effects of High Intensity Training on Pain Processing and Inflammation in Chronic Low Back Pain.
Condition: Low Back Pain; Inflammation
MeSH terms: Inflammation; Back Pain; Low Back Pain
Study type: Interventional

Summary: 
      A multitude of exercise therapy modalities are effective in improving daily physical function
      and relieving pain in various forms of chronic musculoskeletal pain (CMP) such as chronic
      neck pain, osteoarthritis, fibromyalgia, and chronic low back pain. However, the inital pain
      response to physical exercise can be variable in populations with CMP. Indeed, some studies
      show no change or even brief exacerbations in pain in individuals with CMP in response to
      exercise. These pain flare-ups in chronic pain populations are believed to be associated with
      increased pain sensitivity after exercise.

      The magnitude of "exercise-induced hypoalgesia" or the EIH response (i.e., the short-term
      endogenous pain-suppressing response after exercise) is believed to depend on several
      training factors, including exercise intensity. Currently, there is limited understanding of
      the optimal intensity of exercise for producing hypoalgesic effects on different types of
      pain stimuli. Nevertheless, several indications have been found for a dose-response effect in
      exercise and the amount of EIH that can be expected. However, very few studies have
      specifically examined EIH in people with chronic low back pain, although exercise is
      recommended in national and international guidelines as a basic treatment for the treatment
      of this condition.

      Relevant studies have also shown that exercise can induce an extensive inflammatory response
      in CMP, which may contribute to the disrupted EIH production. In addition, it is stated that
      this inflammatory response in CMP is also influenced by psychosocial factors.

      Therefore, the aim of the current cross-sectional cohort study is to expand the knowledge of
      the pain processing and inflammatory response to acute physical exertion in persons with
      chronic low back pain through evaluation responses of persons with this disorder to a high
      intensity training protocol. It is also investigated whether their EIH response is dependent
      on psychosocial factors.
    

Detailed description: 
      Chronic musculoskeletal pain (CMP) currently affects up to 20% of all people or about 1.5
      billion persons worldwide, and these numbers continue to increase steadily. CMP can have a
      significant impact on both the physical and psychological functioning of an individual with
      consequences including recurring health care costs, limitation of participation in society,
      and long-term absenteeism. This makes CMP a pervasive medical problem that consumes a huge
      amount of healthcare resources.

      Regular physical activity and exercise can impact many aspects of a person's general health
      through improving both physical functioning (e.g. cardiorespiratory fitness), as well as
      psychological functioning (e.g. mental health). Moreover, many common forms of exercise
      therapy have been studied and shown to be effective in relieving pain. These include amongst
      others running, walking, resistance training, water training and Tai Chi. As a result, more
      and more studies are referring to exercise therapy as an accessible, cost-effective and
      cost-effective therapeutic modality for the treatment of almost all types of musculoskeletal
      disorders. For example, substantial evidence already supports that exercise therapy can be
      effective in improving daily physical function and relieving pain in individuals with chronic
      neck pain, osteoarthritis, fibromyalgia and chronic low back pain.

      While exercise therapy thus has clear benefits in persons with CMP, pain response to exercise
      can be variable in these populations, especially in the initial stages of therapy. Indeed,
      some studies show no change or even brief exacerbations of pain in persons with CMP in
      response to exercise. These 'flare-ups' of acute pain during exercise are believed to be
      related to increased chronic pain sensitivity.

      The effect of "exercise-induced hypoalgesia" or EIH (i.e., the short-term endogenous
      pain-inhibiting response after exercise) is well documented in healthy subjects. The
      magnitude of the EIH response is believed to depend on several factors, including the type,
      dose, and intensity of the exercise. While the EIH response, measured as a change in the pain
      threshold after exercise, can be assess with quantitative sensory tests (ie a panel of
      diagnostic tests used to assess somatosensory function), there is currently only limited
      understanding of the optimal exercise intensity to produce hypoalgesic effects on different
      types of pain stimuli. Nevertheless, several indications of a dose-response effect in
      exercise and the amount of EIH that can be expected have been found. Studies have also shown
      that EIH can be affected in a variety of musculoskeletal pain disorders, including whiplash,
      knee osteoarthritis, or shoulder pain. This may explain the varied response to exercise and
      may have important implications for exercise prescription. However, very few studies have
      examined the relationship between exercise modalities and EIH in people with chronic low back
      pain, although exercise is recommended in national and international guidelines as a basic
      treatment for the treatment of this condition.

      Furthermore, research has also shown that exercise can induce an extensive inflammatory
      response in persons with CMP (by drastically changing levels of inflammatory markers at
      various sites in the nervous system), which may heavily contribute to the disrupted
      production of EIH. Specifically, the effect of interleukin-6 (IL-6) during physical
      performance as a potential local "pain trigger" is gaining more and more attention. Recently,
      several pathological pain models have shown significantly increased expression levels of IL-6
      and its receptor in the spinal cord and dorsal root ganglia.

      In addition, these inflammatory responses and EIH are said to be influenced by psychosocial
      factors in chronic pain disorders. For example, higher anxiety and catastrophe resulted in an
      enhanced pro-inflammatory response in fibromyalgia and osteoarthritis. Likewise, sleep
      disturbances resulted in higher IL-6 levels in CLBP. As such, these results suggest that EIH
      can be affected by multiple cellular and molecular events in the pain process as well as
      individual responses to specific situations.

      The objective of this study is to expand the knowledge of the pain processing and
      inflammatory response to acute physical exertion of persons with chronic low back pain. This
      study will also investigate whether these responses are dependent on psychosocial factors.
      The information provided by this study may contribute to a better understanding of the
      mechanisms that lead to varied responses to exercise in people with chronic low back pain.
      This allows therapy protocols to be adapted and the worsening of symptoms in some people with
      chronic low back pain to be counteracted by these therapy protocols.

      Primary research questions:

        -  Question 1: To what extent does a single high or moderately intensive cardiorespiratory
           exercise protocol have an acute effect on pain processing and the inflammatory response
           in persons with chronic low back pain?

        -  Question 2: To what extent is the acute effect of a single high or moderately intensive
           cardiorespiratory exercise protocol on pain processing and the inflammatory response
           correlated with differences in psychosocial parameters in persons with chronic low back
           pain?

        -  Question 3: To what extent is the acute effect of a single high or moderately intensive
           cardiorespiratory exercise protocol on pain processing and the inflammatory response in
           subjects with chronic low back pain different from healthy subjects?
    

Intervention name(s): high intensity cardiorespiratory exercise protocol; moderate intensity cardiorespiratory exercise protocol
Intervention type(s): Other; Other
Intervention description(s): During the high intensive cardiorespiratory exercise protocol, a bicycle ergometer (eBike Basic, General Electric GmbH, Bitz, Germany) with pulmonary gas exchange analysis (MetaMax 3B, Cortex Biophysik GmbH, Leipzig, Germany) will be used. Oxygen uptake (VO2max), expiratory volume (VE) and respiratory exchange rate (RER) will be tracked every breath and an average will be taken every 10s. Heart rate is continuously monitored using a heart rate chest strap (Polar Electro Inc., Finland). After a five-minute warm-up, a high-intensity interval protocol is started, consisting of five one-minute bouts (110 reps/minute at 100% VO2max workload), separated by one minute of active rest (75 reps per minute at 50% VO2max workload).; During the moderate intensive cardiorespiratory exercise protocol, a bicycle ergometer (eBike Basic, General Electric GmbH, Bitz, Germany) with pulmonary gas exchange analysis (MetaMax 3B, Cortex Biophysik GmbH, Leipzig, Germany) will be used. Oxygen uptake (VO2max), expiratory volume (VE) and respiratory exchange rate (RER) will be tracked every breath and an average will be taken every 10s. Heart rate is continuously monitored using a heart rate chest strap (Polar Electro Inc., Finland). After a five-minute warm-up, participants begin a moderately-intensive continuous 14-minute exercise protocol at a stable resistance (90 repetitions per minute at 60% VO2max workload).
Other intervention name(s): physical perfomance intervention; physical perfomance intervention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: group 1: 2 testmoments, min. 7 days and max. 14 days in between them. Both have exactly the same design and the same content of measurements, with the exception of the intensity of the performed exercise protocol. The correct wattage for the exercise protocols is extracted from a previous maximum exercise test at the Jessa Hospital. By means of a randomized cross-over design, participants from group 1 will undergo both a moderately intensive cardiorespiratory protocol (MIT) and a high-intensity cardiorespiratory protocol (HIT).
group 2: 2 testmoments, min. 7 days and max. 14 days in between them. During the first testmoment, a maximum exercise test is performed (to establish the exercise protocol that will be used during the second testmoment). The design and content of the second test moment is identical to that of group 1 with the exception of 1) only performing a HIT protocol and 2) not completing the questionnaires only applicable for persons with low back pain (i.e. ODI, BPI).
Masking: None (Open Label)
Primary purpose: Treatment