Structural White and Gray Matter Correlates of Impaired Muscle Control and Deficient Pain Processing
Condition: Low Back Pain; Low Back Pain, Recurrent; Low Back Pain, Chronic; Healthy Volunteers; Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes; Back Pain; Low Back Pain; Chronic Pain
Study type: Observational

Summary: 
      Although the cause of persistent non-specific low back pain (LBP) remains unknown, structural
      and functional alterations of the brain, alterations in the lumbar muscles and dysfunction of
      the central nervous system have been proposed as underlying mechanisms. In this case-control
      study, 1) brain structure/function, 2) lumbar muscle function and 3) central pain processing
      are compared across four groups: 1) healthy participants, 2) recurrent LBP (both during pain
      flare and during pain remission), 3) chronic LBP and 4) fibromyalgia. According to previous
      research, healthy participants and fibromyalgia patients are two extremes of a
      "musculoskeletal pain continuum". Healthy participants representing one extreme of the
      continuum with no pain and fibromyalgia representing the other extreme of the continuum with
      chronic widespread pain. It is thought that different LBP populations (i.e. (sub)acute,
      recurrent, chronic LBP) float between the aforementioned extremes. Past studies already
      highlighted the need for studies comparing the pathophysiological mechanisms for different
      pain syndromes to identify common underlying mechanisms across pain syndromes. For this
      reason, the goal of the current study is to compare alterations in brain structure/function,
      alterations in lumbar muscle function and alterations in central pain processing across the
      aforementioned "musculoskeletal pain continuum". It is hypothesized that longer duration of
      pain (recurrent vs chronic) and the extensiveness of the pain (one location vs widespread
      pain) are associated with more pronounced alterations in 1) brain structure/function, 2)
      lumbar muscle function and 3) central pain processing.
    

Detailed description: 
      Introduction: Chronic pain is one of the most disabling symptoms in several medical
      conditions, including LBP and fibromyalgia. A crucial factor for the persistence of
      recurrent/chronic pain are alterations in lumbar muscle structure and function in patients
      experiencing recurrent/chronic LBP. Previous studies revealed that these alterations in
      lumbar muscle structure and function do not resolve when patients with recurrent LBP
      experience a pain-free episode. According to other recent studies, dysfunction of the central
      nervous system is another crucial factor to the maintenance of chronic pain. The
      aforementioned alterations in lumbar muscle structure and function could constitute constant
      nociceptive input leading to the development of central sensitization (i.e. heightened
      sensitivity or hyperexcitability of central nervous system). Although it is plausible that
      central sensitization and disturbed pain processing do exist in patients experiencing chronic
      LBP, previous studies investigating these mechanisms are scant and results are inconsistent.
      These inconsistent results might be explained by the fact that previous studies used mixed
      back pain populations (i.e. different types of back pain are included in one study). In
      contrast to the inconsistent evidence for the presence of central sensitization in chronic
      LBP, previous studies in fibromyalgia populations have shown convincing evidence for central
      sensitization and disturbed pain processing in fibromyalgia. It could be possible that the
      long-term presence of pain and nociceptive input not only influence pain processing, but also
      motor control. To support this hypothesis, past studies have revealed altered organization of
      brain areas involved in trunk and lumbar motor control in patients experiencing recurrent
      LBP. In addition to alterations in brain function, changes in brain structure are also
      probable in patients experiencing persistent pain and nociceptive input. Previous studies in
      fibromyalgia already confirmed the presence of structural brain alterations. To date, only
      two studies investigated the presence of structural brain alterations in gray matter in
      patients experiencing LBP and the results are contradicting. Whether structural brain
      alterations in white matter exist in patients experiencing LBP has not yet explored in
      previous studies. Past studies in fibromyalgia do confirm that white matter structural
      changes exist. It is still unclear which specific properties of white matter change in
      patients with fibromyalgia, because more advanced imaging techniques are necessary to answer
      this question. In our current study we want to elaborate on the aforementioned results
      obtained in fibromyalgia patients to investigate whether the same alterations in central
      mechanisms (i.e. altered pain processing and alterations in brain structure/function) occur
      in patients experiencing recurrent/chronic LBP. Past studies already highlighted the need for
      studies comparing similarities and differences in the pathophysiological mechanisms for
      different pain syndromes to identify similarities in underlying mechanisms across different
      pain syndromes (e.g. fibromyalgia and LBP). For this reason, the current study will include
      both patients with fibromyalgia and patients experiencing recurrent/chronic LBP to allow for
      comparison of the pathophysiological mechanisms.

      This case-control study has multiple goals: 1) investigate whether central sensitization and
      disturbed central pain processing are present in patients experiencing recurrent and chronic
      LBP. 2) investigate whether structural alterations in gray and white matter exist in patients
      experiencing recurrent and chronic LBP. 3) investigate whether alterations in white matter
      microstructure exist in patients experiencing recurrent and chronic LBP and if these
      alterations are comparable to alterations in white matter structure in fibromyalgia reported
      in previous studies. 4) investigate whether there is an association between alterations in
      brain structure/functional connectivity and the degree of disturbances in pain processing. 5)
      investigate whether there is an association between alterations in brain structure/functional
      connectivity and lumbar muscle dysfunction. 6) investigate to what extent the duration of
      pain (i.e. (sub)acute, recurrent, chronic) and the extensiveness of pain (i.e. one location
      vs widespread pain) influences lumbar motor control, pain processing and brain
      structure/function.

      Method: In this case-control study, 80 female participants will be divided over 4 groups: 1)
      healthy participants (N=20), 2) recurrent non-specific LBP patients, both during pain
      remission and during pain flare pain (N = 20), 3) chronic non-specific LBP (N = 20) and 4)
      fibromyalgia patients (N = 20). The test protocol consists of three parts: 1) participants
      complete a series of questionnaires measuring several clinical characteristics, including:
      sociodemographic variables, pain intensity, functional disability, central sensitization and
      psychosocial factors (i.e. coping, catastrophizing, kinesiophobia, hypervigilance and
      anxiety/depression). 2) magnetic resonance imaging (MRI) will be used to measure brain
      structure. Functional MRI (fMRI) and diffusion tensor imaging (DTI) will be used to measure
      brain function (i.e. resting state and functional connectivity respectively). 3) a series of
      clinical tests will be performed to measure lumbar muscle function and central pain
      processing. Lumbar muscle function will be evaluated by using surface electromyography (EMG)
      for testing anticipatory postural adjustments (APA) in a rapid arm movement (RAM) task and
      compensatory postural adjustments (CPA) in a quick force release test (QFRT). Central pain
      processing will be assessed by using 1) pressure algometry for determining pain pressure
      thresholds (PPT), 2) measuring PPT after a conditioned pain modulation paradigm (CPM) and 3)
      by determining the nociceptive flexion reflex (NFR) threshold by using repetitive
      transcutaneous electrical nerve stimulation (TENS) of the n. suralis.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        All participants are women, recruited through advertisement in hospitals, patient groups
        and organizations, flyers, social media etc.
      
Keywords: low back pain; motor control; central sensitization; brain structure; brain function; central pain processing; fibromyalgia