Mindfulness physical therapy, pain management, rehabilitation

Stress, Sleep Disturbance, Glial Activation and Pain

In a recent review article, Nijs and colleagues examine the role of chronic or severe stress and sleep disturbance in promoting aberrant glial activity which, in turn, may contribute to central sensitization and persistent pain conditions.1 Glial cells are non-neuronal cells that provide support and protection to neurons. Major central nervous system (CNS) glial cell types are microglia, astrocytes and oligodendrocytes. Glial cells respond to injury or infection in a coordinated manner to repair damage and restore brain homeostasis.

Stress and the consequent increased noradrenaline and glucocorticoid levels can cause an over-activation of microglia that results in low grade inflammation and an increased excitability of CNS neurons. Glucocorticoids have been shown to “prime” microglia leading to an exaggerated pro-inflammatory cytokine response to subsequent challenges.

And while adequate, restful sleep promotes immune health, sleep loss results in low grade pro-inflammatory responses, possibly mediated by microglia. In addition, a review and meta-analysis of sleep disturbance, sleep duration and inflammation found sleep disturbance to be associated with higher levels of CRP and IL-6, shorter sleep duration to be associated with higher levels of CRP, and extreme long sleep duration to be associated with higher levels of CRP and IL-6.2

Authors identify the need for additional human studies that examine the role of excessive glial activation in CNS inflammation, central sensitization and persistent pain conditions. They also suggest that stress management strategies, improved sleep hygiene and exercise therapy are potential treatment approaches that could mitigate aberrant glial activity and CNS inflammation associated with chronic or severe stress and disturbed sleep and potentially temper their impact on persistent pain conditions.


1Nijs J, Loggia ML, Polli A, et al. Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients? Expert Opin Ther Targets. 2017; 21(8):817-826.
2Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration and inflammation: A systematic review and meta-analysis of cohort and experimental sleep deprivation. Biopsychiatry. 2016;80(1):40-52.