Expression of substance P and vanilloid receptor (VR1) in trigeminal sensory neurons projecting to the mouse nasal mucosa

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 VRI and substance P to investigate the occurrence and distribution of substance P and VR I 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 VR I and substance P were found with different frequencies: 11.3 +/- 1.2% (mean SEM) were immunoreactive for VR 1, 4.9 +/- 1.1% for VR I and SP, and 6.4 +/- 1.3% only for VR I but not for SP. These VR I-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 VRI co-localization in nasal afferent neurons, the present study suggests that, following a peripheral activation of the VRI receptor on SP afferents, there could be a triggering of SP-mediated phenomena, including those related to inflammation, such as plasma extravasation. (C) 2003 Elsevier Science Ltd. All rights reserved.