<p>The P2X receptor is an extracellular adenosine triphosphate (ATP)-gated ion channel that plays critical roles in cellular and developmental processes, including cell proliferation, survival, and differentiation. Specifically, P2X3 is essential for ATP to function as a neurotransmitter in the peripheral nervous system. Despite the role of P2X3 in nociception, its specific contribution to the development of the trigeminal ganglion (TG), particularly across different developmental stages, remains undetermined. Therefore, in this study, we measured P2X3 expression in the mouse TG and peripheral tissues, investigated its function in the newborn mouse with P2X3 antagonist, and evaluated its effects using a microarray analysis. We investigated the size and number of P2X3-positive neurons in the TG and the density of P2X3-positive nerve fibers in peripheral tissues of newborn and adult mice using immunohistochemical techniques. P2X3-immunoreactivity occurred in 97.9% of the sensory neurons in the TG at P0 (postnatal day 0); however, the proportion of P2X3-positive TG neurons gradually decreased over time. By adulthood, only 45.0% of sensory neurons in the TG were immunoreactive for P2X3; these neurons were predominantly small- to medium-sized. In the vibrissa, the rate of P2X3-immunoreactive peripheral nerve fibers was significantly higher at P0 than at the adult stage, with a notable decrease during maturation. Notably, administration of a P2X3 antagonist to the vibrissal pad led to reduced leptin receptor transcription in TG neurons of neonatal mice. Collectively, these findings suggest that P2X3 plays a crucial role in the development and maturation of the TG and its associated peripheral regions.</p>