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.
Background: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation techniques that are being explored as therapeutic alternatives for the management of various chronic pain conditions. Objective: The primary objective of this systematic review is to assess the efficacy of TMS and tDCS in reducing clinical pain intensity in chronic orofacial pain (OFP) disorders. The secondary objectives are to describe adverse effects, duration of relief, and TMS/tDCS methodologies used in chronic OFP disorders. Methods: A search was performed in MEDLINE, Embase, Web of Science, Scopus, and Google Scholar. Inclusion criteria were 1) population: adults diagnosed with chronic OFP including neuropathic and non-neuropathic disorders; 2) intervention: active TMS or tDCS stimulation regardless of the used protocol; 3) comparison: sham TMS or tDCS stimulation; and 4) outcome: primary outcome was patient reported pain intensity. Secondary outcomes were duration of pain relief, adverse effects, and methodological parameters. Risk of bias and quality of study reporting were also assessed. Results: A total of 556 individual citations were identified by the search strategy, with 14 articles meeting selection criteria (TMS=11; tDCS=3). Data were obtained for a total of 228 patients. Included OFP disorders were trigeminal neuralgia, trigeminal neuropathy, burning mouth syndrome, atypical facial pain, and temporomandibular disorders. Significant pain reductions were obtained in both techniques. More number of sessions yielded to more durable effects. Overall, high risk of bias and poor study quality were found. Conclusion: TMS and tDCS appear to be safe and promising alternatives to reduce pain intensity in different chronic OFP disorders. Additional research effort is needed to reduce bias, improve quality, and characterize optimal brain stimulation parameters to promote their efficacy.