Substance P and neurokinin A (NKA) have potent pro-inflammatory effects in the airways. The release of these neuropeptides from primary afferent (sensory) nerve endings to various stimuli is considered to be induced by activation of the capsaicin (vanilloid) receptor (VR1). In this study, retrograde neuronal tracing studies were combined with immunohistochemistry for VR1 and substance P to investigate the occurrence and distribution of substance P and VR1 receptor expression in mouse trigeminal neurons that were identified by retrograde labeling with Fast blue dye from the nasal mucosa. Fast blue signaling was observed in mucosa layers of the right nasal cavity and in sensory trigeminal neurons close to the division of the ophthalmic and maxillary nerve. Expression patterns of VR1 and substance P were found with different frequencies: 11.3+/-1.2% (mean+/-SEM) were immunoreactive for VR1, 4.9+/-1.1% for VR1 and SP, and 6.4+/-1.3% only for VR1 but not for SP. These VR1-positive neurons were partly binding to lectin I-B4, indicating VR1-expression in non-peptidergic upper airway C-fibers. In conclusion, based on the extent of SP and VR1 co-localization in nasal afferent neurons, the present study suggests that, following a peripheral activation of the VR1 receptor on SP afferents, there could be a triggering of SP-mediated phenomena, including those related to inflammation, such as plasma extravasation.