The role of histamine in narcolepsy type 1: a narrative review

Narcolepsy type 1 (NT1) is a chronic neurological disorder characterized mainly by impaired wakefulness maintenance and dysregulated rapid eye movement (REM) sleep, which markedly affects patients' daytime functioning and quality of life. The core pathological basis of NT1 is the selective loss of orexinergic neurons. The orexinergic system regulates histaminergic neurons in the tuberomammillary nucleus (TMN) through anatomical projections and functional excitation, while the histaminergic system contributes to cortical activation, arousal maintenance, and attention regulation. Therefore, the orexinergic and histaminergic systems can be regarded as interconnected and functionally complementary components of the arousal network. Previous studies have suggested alterations in histaminergic signaling in NT1, although the specific mechanisms underlying its role in NT1 remain incompletely understood. Current evidence suggests that histamine may play a modulatory role in NT1-associated phenotypes. This review summarizes the physiological functions of the histaminergic system in arousal regulation and discusses its interaction with the orexinergic system. It further analyzes the role of HA in NT1, its influence on clinical phenotypes, and related therapeutic strategies, with the aim of providing insights for mechanistic research and precision treatment of NT1.