Acute Effects of High Intensity Training on Pain Processing and Inflammation in Chronic Low Back Pain.

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.

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?

Eligibility Criteria:
Inclusion criteria for group 1 (persons with chronic low back pain)

* Primary complaint: non-specific chronic low back pain.

  * Low back pain is defined as pain in the area between the lower ribs and the upper buttock crease, with or without radiation in the leg
  * Chronic: current episode \> 12 weeks, mean pain intensity between 3-8/10
  * Non-specific: the main pain cannot be traced back to a known pathology
* Age: 18-65 years
* Acute pain intensity at the time of testing between 3-8/10 (i.e. a pain intensity within this range is necessary to obtain a correct estimate of the pain response)
* Understanding of the Dutch language (written and spoken)

Inclusion criteria for group 2 (healthy persons)

* No acute or chronic musculoskeletal complaints (i.e. VAS\> 2/10 in the last 24 hours)
* Age: 18-65 years
* Understanding of the Dutch language (written and spoken)

Exclusion criteria for both group 1 and 2

* Invasive spinal surgery within the last 18 months (arthrodesis will always be excluded, microsurgery is allowed)
* Radiculopathy (uni- or bilateral) of the lower extremities
* Comorbidities: paresis and sensory disturbances with a neurological cause in the lower extremities, diabetes mellitus, rheumatoid arthritis, autoimmune disorders etc.
* Pregnancy
* Ongoing compensation complaints and/or incapacity for work \> 6 months
* Previous active rehabilitation (i.e. exercise therapy) for low back pain in the last 6 months.