[Recent Advances in Trigeminal Nerve Understanding: Anatomy, Pathophysiology, and Emerging Therapeutic Targets]

The trigeminal nerve, the largest cranial nerve, has both sensory and motor fibers responsible for facial sensation and mastication. This article reviews the anatomy, clinical examination, and imaging findings of the trigeminal nerve, followed by an overview of its major disorders, including trigeminal neuralgia, painful trigeminal neuropathy attributed to herpes zoster, trigeminal postherpetic neuralgia, and trigeminal autonomic cephalalgia. Recent advances in neuropeptide research have identified calcitonin gene-related peptides (CGRP) and pituitary adenylate cyclase-activating polypeptides (PACAP) as the key molecular targets for trigeminal nerve associated migraine therapy. Moreover, emerging evidence suggests that the MERTK-Galectin-3 signaling pathway may contribute to the pathophysiology of cluster headaches and peripheral sensitization. The discovery of robust circadian rhythms within the trigeminal ganglion further highlights the potential association between headache chronobiology and the timing of drug administration, suggesting a novel concept of chronotherapy in headache management. Collectively, these findings further our understanding of the trigeminal system from anatomical, molecular, and chronobiological perspectives, and may lead to more targeted and time-sensitive therapeutic approaches for primary headache disorders.