Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, Maine 04005, USA.
Invest Ophthalmol Vis Sci. 2012 Oct 9;53(11):7034-42. doi: 10.1167/iovs.12-10025.
Stimulation to the cornea via noxious chemical and mechanical means evokes tearing, blinking, and pain. In contrast, mild cooling of the ocular surface has been reported to increase lacrimation via activation of corneal cool primary afferent neurons. The purpose of our study was to determine whether menthol induces corneal cool cell activity and lacrimation via the transient receptor potential melastatin-8 (TRPM8) channel without evoking nociceptive responses.
Tear measurements were made using a cotton thread in TRPM8 wild type and knockout mice after application of menthol (0.05-50 mM) to the cornea. In additional studies, nocifensive responses (eye swiping and lid closure) were quantified following cornea menthol application. Trigeminal ganglion electrophysiologic single unit recordings were performed in rats to determine the effect of low and high concentrations of menthol on corneal cool cells.
At low concentrations, menthol increased tear production in TRPM8 wild type and heterozygous animals, but had no effect in TRPM8 knockout mice, while nocifensive responses remained unaffected. At the highest concentration, menthol (50 mM) increased tearing and nocifensive responses in TRPM8 wild type and knockout animals. A low concentration of menthol (0.1 mM) increased cool cell activity, yet a high concentration of menthol (50 mM) had no effect.
These studies indicated that low concentrations of menthol can increase lacrimation via TRPM8 channels without evoking nocifensive behaviors. At high concentrations, menthol can induce lacrimation and nocifensive behaviors in a TRPM8 independent mechanism. The increase in lacrimation is likely due to an increase in cool cell activity.
通过有害的化学和机械刺激角膜会引起流泪、眨眼和疼痛。相比之下，据报道，轻度冷却眼表面会通过激活角膜冷敏初级传入神经元来增加泪液分泌。我们的研究目的是确定薄荷醇是否通过瞬时受体电位 melastatin-8（TRPM8）通道诱导角膜冷细胞活性和流泪，而不会引起伤害性反应。
在 TRPM8 野生型和敲除小鼠的角膜上涂抹薄荷醇（0.05-50mM）后，使用棉线测量泪液量。在其他研究中，量化了角膜涂抹薄荷醇后的伤害性反应（眼睛擦拭和眼睑闭合）。在大鼠中进行三叉神经节电生理单细胞记录，以确定低浓度和高浓度薄荷醇对角膜冷细胞的影响。
在低浓度下，薄荷醇增加了 TRPM8 野生型和杂合动物的泪液分泌，但对 TRPM8 敲除小鼠没有影响，而伤害性反应仍然不受影响。在最高浓度下，薄荷醇（50mM）增加了 TRPM8 野生型和敲除动物的流泪和伤害性反应。低浓度的薄荷醇（0.1mM）增加了冷细胞的活性，而高浓度的薄荷醇（50mM）则没有影响。
这些研究表明，低浓度的薄荷醇可以通过 TRPM8 通道增加泪液分泌而不引起伤害性行为。在高浓度下，薄荷醇可以通过 TRPM8 独立的机制引起流泪和伤害性行为。泪液分泌的增加可能是由于冷细胞活性的增加。
