Substance P released from sensory nerve endings influences tear secretion and goblet cell function in the rat.

The aim of this study was to present morphological and functional evidence to evaluate whether tear secretion is influenced by neuropeptides released from sensory nerve endings of the conjunctiva. Following unilateral electrical stimulation of the trigeminal ganglion, tears were collected at both sides and assessed for volume and protein concentration; as well as gel electrophoresis and luminol chemiluminescence with immunostaining to immunoglobulin A and lysozyme measurements. Goblet cell density (goblet cells/100 basal cells) was recorded during histopathological examination of removed lids. Rats were pretreated with atropine to block parasympathetic; guanethidine to block sympathetic neuronal pathways; or hexamethonium to block synaptic transmission in ganglia. Capsaicin was used to deplete neurotransmitters from sensory nerve endings or SR140333 to block substance P tachykinin NK1 receptor mediated responses. Effects of inadequate electrode position or incidental lesion of trigeminal ganglion were examined by placing the electrode in false position, or no stimulation at a correct position. Electrical stimulation resulted in 380% increase of tear secretion (p < 0.001) and 30% decrease of goblet cell density (p < 0.001) on the the stimulated side compared to the unstimulated side. Atropine, guanethidine and hexamethonium pretreatments had no effect (p > 0.05), but capsaicin and SR140333 inhibited the effect of stimulation (by 96% and 72%, respectively, p < 0.001). Inadequate stimulation did not increase the tear secretion (p < 0.05). Protein concentration decreased, whilst tear volume and total secreted protein increased (p < 0.005) after stimulation. Electrophoresis showed no difference in protein pattern between stimulated and control side and analysis of equivalent amount of tear protein with luminol chemiluminescence indicated no difference in immunoglobulin A and lysozyme ratio following stimulation (p>0.05). We conclude that antidromic electrical activation of conjunctival sensory nerve endings significantly increases water, mucus and protein phases of tear. It is suggested that the sensory neuropeptide substance P plays a pivotal role in this neurogenic regulatory mechanism.