EFFECTS OF SILICA EXPOSURE ON SUBSTANCE-P IMMUNOREACTIVITY AND PREPROTACHYKININ MESSENGER-RNA EXPRESSION IN TRIGEMINAL SENSORY NEURONS IN FISCHER-344 RATS

Trigeminal sensory neurons innervate the nasal cavity and may release substance P (SP) upon exposure to inhaled irritants. The purpose of th is study was to determine if silica dust, an occupational irritant cau sing inflammation, activates sensory neurons supplying the nasal cavit y. Male Fischer 344 rats were placed in inhalation chambers and expose d daily to 2 mg/m(3) of fresh silica (average diameter 1 mu m) for 6 m o. Following exposure, the trigeminal ganglia (TG) were removed and pr epared for SP immunocytochemistry and for preprotachykinin (PPT) autor adiographic in situ hybridization. The SP-like immunofluorescence in T C neurons was subjectively categorized as high, moderate, or low (back ground) intensity. In situ hybridization autoradiographs were quantifi ed on the basis of grain density using digital imaging analysis. The S P immunoreactivity and PPT mRNA expression in the TG neurons were sign ificantly increased after silica inhalation. The proportion of highly positive SP-immunoreactive neurons shifted from 1.30 +/- 0.58% in cont rols Co 11.30 +/- 1.15% after silica treatment. The neurons exhibiting high grain density for PPT mRNA increased from 1.50 +/- 0.87% in cont rols to 11.67 +/- 0.58% in the silica group. Thus, inhalation of silic a causes upper airway irritation resulting in increased levels of immu noreactive neuronal SP and PPT mRNA. These findings suggest that silic a activates sensory pathways that may be involved in nasal inflammatio n.