Dry eye modifies the thermal and menthol responses in rat corneal primary afferent cool cells

Abstract

Kurose M, Meng ID. Dry eye modifies the thermal and menthol responses in rat corneal primary afferent cool cells. J Neurophysiol 110: 495-504, 2013. First published May 1, 2013 doi:10.1152/jn.00222.2013.-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 M-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 mentholinduced desensitization of corneal cool cells would likely result in reduced tearing, a deleterious effect in individuals with dry eye.

Physiological temperatures drive glutamate release onto trigeminal superficial dorsal horn neurons

“…Data in C-F represent the means Ϯ SE. Statistical significance was *P Յ 0.05. during extracellular in vivo recordings from the Vc (Kurose and Meng 2013), something that we rarely observed in the central responses (1 of 151 recordings). Remarkably, increases in temperature directly increased glutamate release in most of the Vc neurons tested.…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Importantly, at concentrations at which it increased tear production, menthol did not evoke nocifensive behavior, nor did it interfere with protective eye reflexes. Taken together, these findings imply that a TRPM8 agonist-containing eye drop may be a novel therapeutic approach to stimulate tear production in patients with dry eye disease (Parra et al, 2010;Kurose and Meng, 2013).…”

Functional Properties of Sensory Nerve Terminals of the Mouse Cornea

“…More recently, corneal ''dry-sensitive'' neurons responding to weak or strong levels of ocular surface desiccation, hyperosmolarity, and menthol and exhibiting parallel high or low sensitivity to corneal cooling were reported in the TG of the rat. 30,32,60 Here, we unambiguously identified and characterized these two subclasses of coldthermosensitive neurons in the mouse cornea and propose their inclusion within the general class of cold thermoreceptor primary sensory neurons.…”

“…A variable sensitivity of canonical cold thermoreceptors to these stimuli has been reported earlier. [17][18][19]24,29,30,32,35,55 This is not exceptional. Other classes of peripheral somatosensory receptors equipped with specific transducing channels that confer preferential sensitivity for a particular form of stimulating energy, also express transduction channels for other stimulus qualities.…”

“…23,24,28,53,54 We distinguished in the mouse cornea a high number of HB-LT cold terminals that typically responded to static and dynamic changes in temperature and were activated by menthol and hyperosmotic stimuli, as reported for canonical cold thermoreceptors of the cornea and of various other tissues in many species. 19,32,[54][55][56][57] In the eye, it has been postulated that these low-threshold corneal thermoreceptors detect small temperature changes linked to interblink tear film evaporation, thereby providing a tonic sensory input to the brain encoding wetness of the eye surface. 17,29,58,59 The additional presence in the cornea of a subpopulation of unmyelinated cold thermoreceptor axons responding only to strong cooling and osmolality was originally reported in the cat in 1993 by Gallar et al, 24 who named them ''cold'' nociceptors.…”