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.

Child Neurology and Psychiatry Unit Systems Medicine Department University Hospital Tor Vergata Viale Oxford 81 00133 Rome Italy

Department of Anaesthesiology and Intensive Care Faculty of Medicine Riga Stradins University Riga Latvia

Department of Applied Clinical Sciences and Biotechnology University of L'Aquila 67100 L'Aquila Italy

Department of Clinical and Experimental Medicine Neurology Unit University of Pisa 56126 Pisa Italy

Department of Clinical Experimental Research Glostrup Research Institute Rigshospitalet Glostrup 2600 Glostrup Denmark

Department of Drug Design and Pharmacology Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark

Department of Internal Medicine Fondazione Policlinico Universitario Agostino Gemelli IRCCS Università Cattolica del Sacro Cuore Rome Italy

Department of Neurology 1st Pavlov State Medical University of St Petersburg St Petersburg Russia

Department of Neurology Headache Center Ospedale Pediatrico Bambino Gesù IRCCS Rome Italy

Department of Neurology St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Neurology University of Rome Tor Vergata Rome Italy

Department of Neurology ZNA Middelheim Lindendreef 1 2020 Antwerp Belgium

Department of Neuroscience University of Sao Paulo Ribeirao Preto Brazil

Department of Neurosurgery 1st Pavlov State Medical University of St Petersburg Lev Tolstoy Street 6 8 St Petersburg Russia

Department of Pain Medicine Hospital Jurmala Jurmala Latvia

Department of Public Medicine Laboratory of Morphology of Neuronal Network University of Campania Luigi Vanvitelli Naples Italy

F F Erisman Federal Research Center for Hygiene Mytishchy Russia

Faculty of Medicine University of Tartu Tartu Estonia

GBUZ Regional Clinical Hospital № 2 Krasnodar Russia

Headache Centre Vivendi Riga Latvia

Headache Research Wolfson CARD Institute of Psychiatry Psychology and Neuroscience King's College London London UK

IRCCS Fondazione Don Carlo Gnocchi Milan Italy

Pain Department Petrovsky National Research Centre of Surgery Moscow Russia

The Headache Centre Guy's and St Thomas NHS Foundation Trust London UK

The Leningrad Regional State Budgetary Institution of health care Children's clinical hospital St Petersburg Russia

Unità Sanitaria Locale Umbria 2 Viale 8 Marzo 05100 Terni Italy

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