Unraveling the Nature of Impaired Pain Inhibition in Patients With Chronic Whiplash-associated Disorders
Condition: Whiplash Injuries
MeSH terms: Whiplash Injuries
Study type: Observational

Summary: 
      The primary study aim is to unravel the nature of impaired pain inhibition during exercise in
      patients with chronic Whiplash-Associated Disorders (WAD). This will be ascertained by
      examining whether activation of serotonergic and/or noradrenergic descending pathways
      improves pain inhibition during exercise in these patients. In addition, it is aimed at
      examining whether activation of serotonergic and/or noradrenergic descending pathways
      prevents post-exertional malaise following submaximal exercise in chronic WAD patients. A
      secondary study aim comprises of examining the effect of an acute submaximal exercise with
      and without activation of serotonergic or noradrenergic descending pathways on chronic WAD
      patients' cognitive performance. Furthermore, the isolated effect of activated serotonergic
      and noradrenergic descending pathways on chronic WAD patients' cognitive performance will be
      studied.
    

Detailed description: 
      Chronic Whiplash-Associated Disorders (WAD) is a debilitating, costly condition, and remains
      a challenge for clinicians, including physicians, rehabilitation specialists and
      physiotherapists. There is now consistent evidence for central sensitization in people with
      chronic WAD. In a previous study in chronic WAD patients, our group showed that pain
      inhibition during exercise is impaired and that a submaximal exercise triggers a severe
      relapse named post-exertional malaise. On the other hand, imbalance of serotonin (5-HT) and
      norepinephrine (NE) is likely to be responsible for malfunctioning of pain inhibitory
      pathways. Indeed, NE is required for activation of descending noradrenergic pathways with
      established nociceptive inhibitory properties. Serotonin reuptake inhibitor drugs activate
      serotonergic descending pathways that recruit, in part, opioid peptide-containing
      interneurons in the dorsal horn. It becomes more and more clear that the lack of pain
      inhibition accounts in part for various symptoms at rest and following exercise in particular
      (post-exertional malaise). However, the mechanisms behind the lack of pain inhibition during
      exercise remain to be revealed. Besides the lack of endogenous pain inhibition during
      exercise in people with chronic WAD, there appears to be sufficient evidence to support the
      presence of impaired cognitive function in chronic pain patients in general and preliminary
      evidence in chronic WAD patients in particular.

      The present study aimed at examining whether activation of serotonergic and/or noradrenergic
      descending pathways improves pain inhibition during exercise in chronic WAD patients. In
      addition, it is aimed at examining whether activation of serotonergic and/or noradrenergic
      descending pathways prevents post-exertional malaise following submaximal exercise in these
      patients. A secondary study aim comprises of examining the effect of an acute submaximal
      exercise with and without activation of serotonergic or noradrenergic descending pathways on
      chronic WAD patients' cognitive performance. Furthermore, the isolated effect of activated
      serotonergic and noradrenergic descending pathways on chronic WAD patients' cognitive
      performance will be studied.We will modulate endogenous serotonergic and adrenergic pain
      inhibitory mechanisms by using a selective NE reuptake inhibitor (NRI) and a selective 5-HT
      reuptake inhibitor (SSRI). Endogenous pain inhibition and cognitive function (sustained and
      selective attention, and executive function) will be studied at rest and in response to
      exercise (1) under baseline condition, (2) after the intake of a NRI (Atomoxetine), and (3)
      after the intake of a SSRI (Citalopram).
    

Intervention name(s): Atomoxetine; Citalopram
Intervention type(s): Drug; Drug
Intervention description(s): 40 mg, 1 application; 20 mg, 1 application
Other intervention name(s): Strattera (Eli Lilly Nederland B.V); Citalopram Sandoz (Sandoz N.V.)
Intervention MeSH terms: Dexetimide; Citalopram; Escitalopram; Atomoxetine Hydrochloride
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        WAD patients: primary care clinic & community sample Healthy people: community sample
      
Keywords: Whiplash Injuries; Chronic Pain; Exercise; Cognition