Spontaneous episodic decreased tear secretion in rats is related to opioidergic signaling pathways.

To elucidate the factors in tear production, this study examined the role of endogenous opioids and opioid receptors in spontaneous episodic reduced tear volume. A model of spontaneous episodic decreases in the quantity of tears was characterized in otherwise normal Sprague-Dawley rats using Schirmer's test. A single eye drop of 10(-5) M naltrexone (NTX), 10(-5) M [Met(5)]-enkephalin, or sterile vehicle was administered to one eye. Tear secretion, corneal sensitivity, and corneal morphology were examined in both eyes. At any given time period, otherwise normal rats were found to have Schirmer test scores with a bimodal distribution (6.5 mm or less, or 7.0 mm or greater). Decreased tear production was detected in male and female rats aged 4 to 24 weeks at least once per animal. The episodes of reduced tear volume ranged from 1 to 7 days. No changes in corneal sensitivity or corneal morphology were observed in any rat. One drop of NTX given to rats with a decrease in tear volume raised levels of tears to scores of 7.0 mm or greater within 1 hour, and increased tear production persisted for at least 48 hours. NTX had no effect on rats with Schirmer scores of 7.0 mm or higher. Topical application of [Met(5)]-enkephalin depressed tear secretion from baseline scores of 9.8 ± 0.6 mm to as low as 4.5 ± 0.7 mm. Normal rats experience fluctuations in tear production that can be modulated by opioidergic signaling pathways.