The Role of Serotonergic and Noradrenergic Descending Pathways on Performance-Based Cognitive Functioning at Rest and in Response to Exercise in People with Chronic Whiplash-Associated Disorders: A Randomized Controlled Crossover Study

Iris Coppieters; Jo Nijs; Mira Meeus; Margot De Kooning; Emma Rheel; Eva Huysmans; Roselien Pas; Wouter Van Bogaert; Ives Hubloue; Kelly Ickmans

doi:10.3390/clinpract13030063

The Role of Serotonergic and Noradrenergic Descending Pathways on Performance-Based Cognitive Functioning at Rest and in Response to Exercise in People with Chronic Whiplash-Associated Disorders: A Randomized Controlled Crossover Study

Clin Pract. 2023 Jun 6;13(3):684-700. doi: 10.3390/clinpract13030063.

Authors

Iris Coppieters^{1

2

3}, Jo Nijs^{1

2

4

5}, Mira Meeus^{3

6}, Margot De Kooning^{1

2}, Emma Rheel^{1

7}, Eva Huysmans^{1

2

8}, Roselien Pas^{1

6}, Wouter Van Bogaert¹, Ives Hubloue⁹, Kelly Ickmans^{1

2

10}

Affiliations

¹ Pain in Motion Research Group (PAIN), Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
² Department of Physical Medicine and Physiotherapy, University Hospital Brussels, 1090 Brussels, Belgium.
³ Department of Rehabilitation Sciences, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
⁴ Department of Health and Rehabilitation, Unit of Physiotherapy, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
⁵ Vrije Universiteit Brussels, Brussels Health Campus Jette, Erasmus Building, PAIN-KIMA, Laarbeeklaan 121, BE1090 Brussels (Jette), Belgium.
⁶ Movant, Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
⁷ Department of Experimental-Clinical and Health Psychology and Educational Sciences, Ghent University, 9000 Ghent, Belgium.
⁸ Department of Public Health (GEWE), Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, 1090 Brussels, Belgium.
⁹ Department of Emergency Medicine, University Hospital Brussels, 10090 Brussel, Belgium.
¹⁰ Research Foundation-Flanders (FWO), 1090 Brussels, Belgium.

Abstract

(1) Background: Dysregulation in serotonergic and noradrenergic systems may be implicated in the neurobiophysiological mechanisms underlying pain-related cognitive impairment in chronic whiplash-associated disorders (CWAD). This study aimed to unravel the role of serotonergic and noradrenergic descending pathways in cognitive functioning at rest and in response to exercise in people with CWAD. (2) Methods: 25 people with CWAD were included in this double-blind, randomized, controlled crossover study. Endogenous descending serotonergic and noradrenergic inhibitory mechanisms were modulated by using a single dose of a selective serotonin reuptake inhibitor (Citalopram) or a selective norepinephrine reuptake inhibitor (Atomoxetine). Cognitive performance was studied at rest and in response to exercise (1) without medication intake; (2) after intake of Citalopram; and (3) after intake of Atomoxetine. (3) Results: After Atomoxetine intake, selective attention improved compared with the no medication day (p < 0.05). In contrast, a single dose of Citalopram had no significant effect on cognitive functioning at rest. When performing pairwise comparisons, improvements in selective attention were found after exercise for the no medication condition (p < 0.05). In contrast, after intake of Citalopram or Atomoxetine, selective and sustained attention worsened after exercise. (4) Conclusions: A single dose of Atomoxetine improved selective attention only in one Stroop condition, and a single dose of Citalopram had no effect on cognitive functioning at rest in people with CWAD. Only without medication intake did selective attention improve in response to exercise, whereas both centrally acting medications worsened cognitive performance in response to a submaximal aerobic exercise bout in people with CWAD.

Keywords: chronic whiplash-associated disorders; cognition; norepinephrine; serotonin.

Grants and funding

This research was partly funded by the Scientific Fund Willy Gepts of the University Hospital Brussels, grant number WFWG-22. Iris Coppieters, a postdoctoral researcher at Vrije Universiteit Brussel, is funded by the Research Foundation Flanders (FWO) [G007217N], Belgium. Eva Huysmans is a PhD research fellow funded by the Research Foundation Flanders (FWO) [1108619N], Belgium. Roselien Pas and Emma Rheel are funded by a Chair awarded by the Berekuyl Academy/European College for Decongestive Lymphatic Therapy, the Netherlands, to the Vrije Universiteit Brussel, Belgium. Wouter Van Bogaert is funded by the Agency for Innovation by Science and Technology (IWT)—Applied Biomedical Research Program (TBM) [150180].