Post-traumatic headache (PTH) is a debilitating condition that affects individuals with different levels of traumatic brain injury (TBI) severity. The difficulties in developing an effective treatment are related to a lack of understanding the complicated mechanisms and neurobiological changes in brain function after a brain injury. Preclinical studies have indicated that peripheral and central sensitization of the trigeminal nociceptive pathways contributes to PTH. While recent brain imaging studies have uncovered widespread changes in brain functional connectivity following trauma, understanding exactly how these networks contribute to PTH after injury remains unknown. Stimulation of peripheral (trigeminal or vagus) nerves show promising efficacies in PTH experimental animals, likely mediated by influencing TBI-induced pathological plasticity by decreasing neuroinflammation and neuronal apoptosis. Non-invasive brain stimulations, such as transcranial magnetic or direct current stimulations, show analgesia for multiple chronic pain conditions, including PTH. Better mechanistic understanding of analgesia achieved by neuromodulations can define peripheral and central mechanisms involved in the development, the resolution, and the management of PTH.

Background/Objectives: Spinal cord injury (SCI) is a devastating condition that leads to a cascade of cellular and molecular events, resulting in both primary and secondary damage. Among the many cells involved in the post-SCI environment, glial cells in the spinal cord and brain are pivotal in determining the trajectory of injury and repair. Methods: While recent SCI studies have shown changes in the genotype of glial cells following injury, exactly how these alterations occur after damage remains unknown. In this sense, the systemic inflammatory molecules could be involved in the connection between the spinal cord and brain, inducing glial activation by different signaling pathways. Preclinical studies have shown that nuclear factor-κB (NF-κB), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways are involved in the change in glial type. Results: These cells, which include astrocytes and microglia, exhibit dynamic responses following spinal injury, contributing to both neuroprotection and neurodegeneration. These different effects indicate that the molecular environment causes changes in the type of astrocytes and microglia, leading to different actions. Conclusions: Understanding the mechanisms of glial cell activation, it is possible to clarify the roles of these glial cells in pathophysiology and their potential repair mechanisms post-injury.