Cannabinoids increase mechanosensitivity of trigeminal ganglion neurons innervating the inner walls of rat anterior chambers via activation of TRPA1

Abstract

Our previous study found that some trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1 (TRPA1) was an essential mechanosensitive channel in the membrane. To address the effect of cannabinoids on the mechanosensitive TG nerve endings in the inner walls of anterior chambers of rat eye, we investigated the effect of the (R)-(+)-WIN55, 212-2 mesylate salt (WIN), a synthetic cannabinoid on their cell bodies in vitro. Rat TG neurons innervating the inner walls of the anterior chambers were labeled by 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfona (FAST DiI). Whole cell patch clamp was performed to record the currents induced by drugs and mechanical stimulation. Mechanical stimulation was applied to the neurons by buffer ejection. WIN evoked inward currents via TRPA1 activation in FAST DiI-labeled TG neurons. WIN enhanced mechanosensitive currents via TRPA1 activation in FAST DiI-labeled TG neurons. Our results indicate that cannabinoids can enhance the mechanosensitivity of TG endings in the inner walls of anterior chambers of rat eye via TRPA1 activation.

Anatomic Evidence for Information Exchange between Primary Afferent Sensory Neurons Innervating the Anterior Eye Chamber and the Dura Mater in Rat

“…[6][7][8] Our previous studies proved that mechanosensitive TG nerve endings innervate the inner wall of the anterior eye chamber (IWAEC), where aqueous circulation takes place, and that the transient receptor potential ankyrin-1 (TRPA1) is an essential mechanosensitive channel in the membranes of the TG nerve endings. [9][10][11] These results gave a possible answer as to how IOP variation triggers action potentials of the TG nerve. We proposed that mechanosensitive TG nerve endings might act as IOP baroreceptors in neural regulation of the IOP.…”

“…30 Intriguingly, our recent study indicated that some TG nerve endings innervating the IWAEC are also mechanically sensitive, and that TRPA1 is an important mechanotransducer in the membrane. [9][10][11] Accumulating evidence has shown that mechanosensitive TG nerve endings in the IWAEC may play a role in IOP sensing. [6][7][8][9][10][11]31,32 Previously, we did not know how an acute IOP elevation could evoke serious eye pain with an ipsilateral headache.…”

“…[9][10][11]18 Briefly, the rats were topically anesthetized with 0.4% oxybuprocaine hydrochloride eye drops after anesthesia with chloral hydrate and a borosilicate glass pipette with a 10-to 15-lm diameter tip was inserted through the cornea into the anterior chamber of the right eye. Caution was used to avoid injuring the iris and lens.…”

“…We proposed that mechanosensitive TG nerve endings might act as IOP baroreceptors in neural regulation of the IOP. [9][10][11] …”