Nasal sensory nerve populations responding to histamine and capsaicin

Background: Inflammation of the nasal mucosa leads to sneezing, nasal itch, rhinorrhea, and nasal blockage. Many of these symptoms are likely the result of nasal trigeminal sensory nerve stimulation by inflammatory mediators. Nasal challenge with the C-fiber stimulant capsaicin causes a different set of symptoms than those evoked by histamine, suggesting that these 2 stimuli may activate separate subpopulations of nasal sensory nerves. Objective: To investigate the trigeminal sensory nerves innervating the guinea pig nasal mucosa and to address specifically the hypothesis that histamine and capsaicin activate distinct subgroups of these nerves. Methods: Guinea pig trigeminal neurons (retrogradely labeled from the nasal mucosa) were assessed for their responses to histamine and capsaicin by studying changes in the intracellular free calcium concentration, and assessed for substance P immunoreactivity. Results: Only 60% of the nasal-specific trigeminal sensory neurons were found to be capsaicin-sensitive. Histamine stimulated only a subset (<40%) of these capsaicin-sensitive neurons. No nasal-specific capsaicin-insensitive neurons responded to histamine, although about 10% of trigeminal ganglion neurons per se responded to histamine but not capsaicin. Immunohistochemical analysis revealed that most (about 60%) of the sensory neurons innervating the nasal mucosa did not express the neuropeptide substance P, including nearly all large-diameter neurons, but also a significant number of small-diameter neurons (presumably C-fiber neurons). Conclusion: Nasal neurons are not homogenous with respect to chemosensitivity or substance P content. It is likely that this heterogeneity in nasal afferent nerves underlies the differences in nasal responses to specific inflammatory mediators associated with the allergic reaction.