The fifth cranial nerve is the common denominator for many headaches and facial pain pathologies currently known. Projecting from the trigeminal ganglion, in a bipolar manner, it connects to the brainstem and supplies various parts of the head and face with sensory innervation. In this review, we describe the neuroanatomical structures and pathways implicated in the sensation of the trigeminal system. Furthermore, we present the current understanding of several primary headaches, painful neuropathies and their pharmacological treatments. We hope that this overview can elucidate the complex field of headache pathologies, and their link to the trigeminal nerve, to a broader field of young scientists.

In contrast to the well defined mechanism of merocrine exocytosis, the mechanism of apocrine secretion, which was first described over 180 years ago, remains relatively uncharacterized. We identified apocrine secretory activity in the late prepupal salivary glands of Drosophila melanogaster just prior to the execution of programmed cell death (PCD). The excellent genetic tools available in Drosophila provide an opportunity to dissect for the first time the molecular and mechanistic aspects of this process. A prerequisite for such an analysis is to have pivotal immunohistochemical, ultrastructural, biochemical and proteomic data that fully characterize the process. Here we present data showing that the Drosophila salivary glands release all kinds of cellular proteins by an apocrine mechanism including cytoskeletal, cytosolic, mitochondrial, nuclear and nucleolar components. Surprisingly, the apocrine release of these proteins displays a temporal pattern with the sequential release of some proteins (e.g. transcription factor BR-C, tumor suppressor p127, cytoskeletal β-tubulin, non-muscle myosin) earlier than others (e.g. filamentous actin, nuclear lamin, mitochondrial pyruvate dehydrogenase). Although the apocrine release of proteins takes place just prior to the execution of an apoptotic program, the nuclear DNA is never released. Western blotting indicates that the secreted proteins remain undegraded in the lumen. Following apocrine secretion, the salivary gland cells remain quite vital, as they retain highly active transcriptional and protein synthetic activity.

Background: Headache is a common complication of traumatic brain injury. The International Headache Society defines post-traumatic headache as a secondary headache attributed to trauma or injury to the head that develops within seven days following trauma. Acute post-traumatic headache resolves after 3 months, but persistent posttraumatic headache usually lasts much longer and accounts for 4% of all secondary headache disorders. Main body: The clinical features of post-traumatic headache after traumatic brain injury resemble various types of primary headaches and the most frequent are migraine-like or tension-type-like phenotypes. The neuroimaging studies that have compared persistent post-traumatic headache and migraine found different structural and functional brain changes, although migraine and post-traumatic headache may be clinically similar. Therapy of various clinical phenotypes of post-traumatic headache almost entirely mirrors the therapy of the corresponding primary headache and are currently based on expert opinion rather than scientific evidence. Pharmacologic therapies include both abortive and prophylactic agents with prophylaxis targeting comorbidities, especially impaired sleep and post-traumatic disorder. There are also effective options for non-pharmacologic therapy of posttraumatic headache, including cognitive-behavioral approaches, onabotulinum toxin injections, lifestyle considerations, etc. Conclusion: Notwithstanding some phenotypic similarities, persistent post-traumatic headache after traumatic brain injury, is considered a separate phenomenon from migraine but available data is inconclusive. High-quality studies are further required to investigate the pathophysiological mechanisms of this secondary headache, in order to identify new targets for treatment and to prevent disability.