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Expert Opin Ther Targets. 2017 Aug;21(8):817-826. doi: 10.1080/14728222.2017.1353603. Epub 2017 Jul 12.

Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

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a Department of physiotherapy, human physiology and anatomy , Pain in Motion International Research Group, Vrije Universiteit Brussel , Brussels , Belgium.
b Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Physical Education & Physiotherapy , Vrije Universiteit Brussel , Brussels , Belgium.
c Department of Physical Medicine and Physiotherapy , University Hospital Brussels , Brussels , Belgium.
j MGH/HST A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Harvard Medical School , Charlestown , MA , USA.
d Department of Neurosurgery and Radiology , University Hospital Brussels , Brussels , Belgium.
e Department of Manual Therapy, Faculty of Medicine and Pharmacy , Vrije Universiteit Brussel , Brussels , Belgium.
f Department of Rehabilitation Sciences and Physiotherapy , Ghent University , Ghent , Belgium.
g Department of Rehabilitation Sciences and Physiotherapy , University of Antwerp , Antwerp , Belgium.
h Private Practice for Spinal Manual Therapy , Schepdaal-Dilbeek , Belgium.
i Chronic Pain and Fatigue Research Center , University of Michigan , Ann Arbor , USA.


The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.


Pain; fibromyalgia; low back pain; neuroinflammation; sleep; stress

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