Serotonin depletion amplifies migraine susceptibility through trigeminal ganglion neurons sensitization: Insights from patch clamp recordings in rat model.

Abstract

Serotonin (5-HT) depletion is a critical driver of migraine pathophysiology, yet its precise impact on trigeminal ganglion (TG) neurons remains unclear. This study investigates how 5-HT depletion shapes the "intrinsic neuronal susceptibility" of the first-order TG neurons by analyzing the electrophysiological properties of small-to-medium (SM) and large (L)-sized TG neurons in a rat model using patch-clamp recordings. Our findings reveal that 5-HT depletion significantly heightens the intrinsic susceptibility of TG neurons, with the electrophysiological disparities between SM and L-sized neurons acting as aggravating factors that intensify peripheral sensitization. Although this study focuses on intrinsic neuronal properties, our findings raise the possibility that 5-HT depletion may indirectly influence the functional balance between pro- and anti-nociceptive 5-HT receptor subtypes within the trigeminovascular system, a hypothesis that warrants further investigation. Functionally, this increased neuronal excitability may predispose TG neurons to heightened responsiveness, potentially contributing to hyperalgesia and altered somatosensory processing. By elucidating the role of serotonin in maintaining sensory homeostasis, this study provides critical insights into migraine pathogenesis and highlights the potential for targeted serotonergic therapies to mitigate excessive trigeminovascular activation.