Division of Oral Physiology, Department of Oral Biological Sciences, Niigata University, Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Neurophysiol. 2013 Jul;110(2):495-504. doi: 10.1152/jn.00222.2013. Epub 2013 May 1.
Dry eye syndrome is a painful condition caused by inadequate or altered tear film on the ocular surface. Primary afferent cool cells innervating the cornea regulate the ocular fluid status by increasing reflex tearing in response to evaporative cooling and hyperosmicity. It has been proposed that activation of corneal cool cells via a transient receptor potential melastatin 8 (TRPM8) channel agonist may represent a potential therapeutic intervention to treat dry eye. This study examined the effect of dry eye on the response properties of corneal cool cells and the ability of the TRPM8 agonist menthol to modify these properties. A unilateral dry eye condition was created in rats by removing the left lacrimal gland. Lacrimal gland removal reduced tears in the dry eye to 35% compared with the contralateral eye and increased the number of spontaneous blinks in the dry eye by over 300%. Extracellular single-unit recordings were performed 8-10 wk following surgery in the trigeminal ganglion of dry eye animals and age-matched controls. Responses of corneal cool cells to cooling were examined after the application of menthol (10 μM-1.0 mM) to the ocular surface. The peak frequency of discharge to cooling was higher and the cooling threshold was warmer in dry eye animals compared with controls. The dry condition also altered the neuronal sensitivity to menthol, causing desensitization to cold-evoked responses at concentrations that produced facilitation in control animals. The menthol-induced desensitization of corneal cool cells would likely result in reduced tearing, a deleterious effect in individuals with dry eye.
干眼症是一种由眼表面泪膜不足或改变引起的疼痛病症。初级传入冷觉细胞通过增加反射性流泪来调节眼液状态，以响应蒸发冷却和高渗性。有人提出，通过瞬时受体电位 melastatin 8（TRPM8）通道激动剂激活角膜冷觉细胞可能代表治疗干眼症的潜在治疗干预措施。本研究检查了干眼症对角膜冷觉细胞反应特性的影响，以及 TRPM8 激动剂薄荷醇修饰这些特性的能力。通过去除左侧泪腺在大鼠中创建单侧干眼症。与对侧眼睛相比，泪腺切除使干眼症中的眼泪减少了 35%，并使干眼症中的自发性眨眼次数增加了 300%以上。在手术后 8-10 周，在三叉神经节中对干眼症动物和年龄匹配的对照进行了细胞外单细胞记录。在用薄荷醇（10 μM-1.0 mM）滴眼后，检查角膜冷觉细胞对冷却的反应。与对照组相比，干眼症动物对冷却的放电峰值频率更高，冷却阈值更温暖。干燥条件还改变了神经元对薄荷醇的敏感性，导致在产生对照动物中促进作用的浓度下对冷诱发反应脱敏。薄荷醇诱导的角膜冷觉细胞脱敏可能导致流泪减少，这对干眼症患者是一种有害影响。
