Effects of TRPM8 and TRPV1 agonists on the neural activity of corneal cold thermoreceptors in tear‐deficient guinea pigs

Abstract

PurposeTo characterize the effects of menthol and capsaicin on the activity of corneal cold thermoreceptors in tear‐deficient guinea pigsMethodsThe main lachrymal gland was surgically removed in anesthetized animals. Four weeks later, cold‐sensitive nerve terminal impulse (NTI) activity was recorded from the superfused cornea. The spontaneous and stimulus‐evoked NTI activity was analysed. For thermal stimulation, temperature of perfusion solution was changed from 34°C (basal) down to 20°C (cooling ramp) or up to 50°C (heating ramp). TRP agonists (50–200 μM menthol, 1–10 μM capsaicin) were also added to the perfusion solution. The characteristics of the spontaneous and stimulus‐evoked NTI activity recorded in tear‐deficient and intact corneas before and during perfusion with TRP channel agonists were compared.ResultsRemoval of the lachrymal gland caused sustained reduction of basal and reflex tearing. NTI activity was significantly higher in cold thermoreceptors from tear‐deficient corneas compared with naïve corneas. Response to cooling ramps was also increased. Menthol increased ongoing and stimulus‐evoked activity of all cold thermoreceptors in both intact and tear deficient corneas. Menthol at high concentrations first excited and then inactivated cold thermoreceptors. Only 10% of thermoreceptors were activated by capsaicin.ConclusionsChronic tear deficiency alters the activity of corneal sensory nerve fibers, leading to the development of increased spontaneous activity and abnormal responsiveness to natural stimulation. These changes are particularly prominent in cold thermoreceptor fibers, whose injury‐evoked neuropathic firing seems to be due to altered expression of Na+ and K+ channels involved in impulse generation without changes in the activity of TRP channels involved in sensory transduction.