Capsaicin-induced responses in cornea: behavioral pain in TRPV1 knockout mice and nitric oxide antagonism

Abstract

Purpose: TRPV-1 receptors are non-selective nociceptive cationic channels involved in peripheral pain. S-nitroso-N-penicillamine (SNAP) is a nitric oxide (NO) donor and a potential antinociceptive agent. Thus, the aims of the present work are: 1) to describe the phenotype and the response of corneas of TRPV1^-/- and WT mice to capsaicin (a TRPV1 agonist) stimulus, and 2) to evaluate the antagonism of SNAP to capsaicin in mice corneal epithelial cells in culture.

Methods: TRPV1^-/- and WT mice received 5 µl of eye drops containing 0.1% capsaicin (n=5/group) in the right eye. Changes were compared in corneal transparency, fluorescein staining, tear secretion and behavioral pain assessment through eye wiping counting. Male adult WT mice cornea epithelia was cultured and challenged with (1µM) capsaicin for 01 hour after SNAP (1mM) incubation for 03 hours or not, and submitted to calcium influx assay.

Results: Ocular surface characteristics were not different between the genotypes of naïve mice and the tears secretion was similar among males and females of both groups (p=0.581). After a single capsaicin application, the number of eye wipes was unchanged (p=0.384). Calcium influx in cornea epithelial cells was induced by capsaicin but this event was inhibited by pre incubation with SNAP (679.30±142.20 versus 97.18±37.73 RFU; p=0.017).

Conclusions: Adult TRPV1^-/- mice did not present changes in the ocular surface phenotype. In addition, no difference was observed in behavioral pain responses to high capsaicin stimuli. As SNAP was able to antagonize TRPV1-capasaicin response in vitro, further studies should elucidate alternative mechanisms involving NO, TRPV-1 and corneal pain.