The Putative Role of Neuroinflammation in the Interaction between Traumatic Brain Injuries, Sleep, Pain and Other Neuropsychiatric Outcomes: A State-of-the-Art Review

Abstract

Sleep disturbances are widely prevalent following a traumatic brain injury (TBI) and have the potential to contribute to numerous post-traumatic physiological, psychological, and cognitive difficulties developing chronically, including chronic pain. An important pathophysiological mechanism involved in the recovery of TBI is neuroinflammation, which leads to many downstream consequences. While neuroinflammation is a process that can be both beneficial and detrimental to individuals’ recovery after sustaining a TBI, recent evidence suggests that neuroinflammation may worsen outcomes in traumatically injured patients, as well as exacerbate the deleterious consequences of sleep disturbances. Additionally, a bidirectional relationship between neuroinflammation and sleep has been described, where neuroinflammation plays a role in sleep regulation and, in turn, poor sleep promotes neuroinflammation. Given the complexity of this interplay, this review aims to clarify the role of neuroinflammation in the relationship between sleep and TBI, with an emphasis on long-term outcomes such as pain, mood disorders, cognitive dysfunctions, and elevated risk of Alzheimer’s disease and dementia. In addition, some management strategies and novel treatment targeting sleep and neuroinflammation will be discussed in order to establish an effective approach to mitigate long-term outcomes after TBI.

Effect of resistive exercise on insomnia and sleep quality in postmenopausal women: a randomized controlled trial

“…Exercise is considered as a thermogenic stimulus to improve sleep as increasing temperature is linked to the regulation of sleep by the anterior hypothalamus [34]. Exercise may reduce resting plasma concentrations of pro-inflammatory cytokines, which are linked to sleep disruption and fragmentation [35]. Also, it may increase anti-inflammatory cytokines, consequently improving the quality of sleep [33].…”

Prevalence and risk factors of significant persistent pain symptoms after critical care illness: a prospective multicentric study

“…We also confirm that pain symptoms are common after sepsis but stress that trauma patients are even at higher risk. After traumatic brain injury, some authors have described that headache could be present in more than half of the patients, pain in other sites could be present in 40% of the patients and musculoskeletal pain could be present in more than 80% of the patients after 15 years [ 22 ]. In spite of this common issue after trauma, there is still much to do to fill the gap of knowledge and propose innovative approaches to improve outcomes.…”

Thirty Risk Factors for Alzheimer’s Disease Unified by a Common Neuroimmune–Neuroinflammation Mechanism

“…Zielinski and Gibbons described the neurotoxic pro-inflammatory role of the IL-1β and TNFα inflammatory cytokines and the NLRP3 inflammasome during periods of dysregulated sleep [146]. Chronic insomnia has also been associated with compromised structural integrity of the BBB, which permits increased entry of peripheral immune cells (macrophages) and inflammatory cytokines into the CNS, further contributing to the ongoing neuroinflammation implicated in AD pathogenesis [147]. Therefore, sleep impairment leads to neuroinflammation through increasing levels of pro-inflammatory cytokines (TNFα, IL-6 and IL-1β) and enzymes (COX), which catalyse inflammatory neurochemical processes.…”