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

Abstract

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.

Trait Sensitivity, Anxiety, and Personality Are Predictive of Central Sensitization Symptoms in Patients with Chronic Low Back Pain

“…Regression analysis in the current study found trait anxiety to be a predictor of CSI scores in people with NSCLBP, reflective of the tendency of high trait anxious individuals to react to threats with state anxiety. State anxiety is a stress response, and chronic stress has been identified in animal work as an activator of glial cells in the central nervous system, which may be associated with neuroinflammation and subsequent CS onset or aggravation . It is suggested that discomfort experienced by sensory under‐ or overstimulation constitutes stressors, which leads to a stress response .…”

“…State anxiety is a stress response, and chronic stress has been identified in animal work as an activator of glial cells in the central nervous system, which may be associated with neuroinflammation and subsequent CS onset or aggravation. 50 It is suggested that discomfort experienced by sensory under-or overstimulation 13,51 constitutes stressors, which leads to a stress response. 13,47 Physiological changes occur in the central nervous system in response to stressors, including those associated with autonomic arousal.…”

Lifestyle and Chronic Pain across the Lifespan: An Inconvenient Truth?

“…In addition to stress and physical (in)activity, other lifestyle factors such as sleep are often neglected by clinicians working with people with chronic pain. Insomnia/sleep disturbances constitutes an important example of physiological stressor .…”

Self‐injurious behaviours in rhesus macaques: Potential glial mechanisms

“…Indeed, recent studies have linked severe stress to specific immune activation (Beurel and Lowell ) and glial activation (Nijs et al . ).…”

“…Importantly, the immune system of rhesus monkeys is more similar to humans than the immune systems of rodents, making monkeys the best choice for evaluating and correlating immunologic responses and CNS disease. Indeed, recent studies have linked severe stress to specific immune activation (Beurel and Lowell 2017) and glial activation (Nijs et al 2017).…”