Trigeminal pathways for hypertonic saline- and light-evoked corneal reflexes

Abstract

Cornea-evoked eyeblinks maintain tear film integrity on the ocular surface in response to dryness and protect the eye from real or potential damage. Eyelid movement following electrical stimulation has been well studied in humans and animals; however, the central neural pathways that mediate protective eyeblinks following natural nociceptive signals are less certain. The aim of this study was to assess the role of the trigeminal subnucleus interpolaris/caudalis (Vi/Vc) transition and subnucleus caudalis/upper cervical cord (Vc/C1) junction regions on orbicularis oculi electromyographic (OOemg) activity evoked by ocular surface application of hypertonic saline or exposure to bright light in urethane anesthetized male rats. The Vi/Vc and Vc/C1 regions are the main sites of termination for trigeminal afferent nerves that supply the ocular surface, while hypertonic saline (saline = 0.15-5M) and bright light (light = 5-20k lux) selectively activate ocular surface and intraocular trigeminal nerves, respectively, and excite second-order neurons at the Vi/Vc and Vc/C1 regions. Integrated OOemg activity, ipsilateral to the applied stimulus, increased with greater stimulus intensities for both modalities. Lidocaine applied to the ocular surface inhibited OOemg responses to hypertonic saline, but did not alter the response to light. Lidocaine injected into the trigeminal ganglion blocked completely the OOemg responses to hypertonic saline and light indicating a trigeminal afferent origin. Synaptic blockade by cobalt chloride of the Vi/Vc or Vc/C1 region greatly reduced OOemg responses to hypertonic saline and bright light. These data indicate that OOemg activity evoked by natural stimuli known to cause irritation or discomfort in humans depends on a relay in both the Vi/Vc transition and Vc/C1 junction regions.

Evidence for TRPA1 involvement in central neural mechanisms in a rat model of dry eye

“…This suggested that the reduced spontaneous tear volume in our DE model (~50% reduction) was sufficient to excite ongoing activity of moisture-sensitive corneal afferent fibers that would be expected to increase during ocular surface dryness (Meng and Kurose 2013). These data support previous studies indicating that ocular stimulus intensity coding is a more pronounced feature of Vc/C1 neurons compared to Vi/Vc transition neurons (see Bereiter et al 2000), whereas the Vi/Vc transition may be more involved in homeostatic reflex responses such as lacrimation and eyeblink (Hirata et al 2004; Rahman et al 2014) and maintenance of a stable tear film.…”

Abnormal trigeminal sensory processing in obese mice

“…41 Second order neurons in this region of the TNc (trigeminal subnucleus caudalis/upper cervical cord junction) also showed increased Fos upon activation by bright light in rats 33 and are required for light-induced blink reflexes. 36 The pattern of light-evoked Fos 33 overlaps with the vibrissal dermatome in the rat TNc 48 and the area of Fos expression in our previous study. 41 …”

Corneal Sensitivity to Hyperosmolar Eye Drops: A Novel Behavioral Assay to Assess Diabetic Peripheral Neuropathy

“…26,27 However, our studies demonstrate that squinting is also associated with activation of osmolarity sensing channels in the cornea of the rat. Rahman et al 28 show that hypertonic saline applied to the ocular surface of the rat elicits orbicularis muscle activity, which is dose dependent and is eliminated by corneal anesthesia, as well as by the blockade of trigeminal ganglion neurons. Recently, in the mouse, activation of TRPM8 channels in the cornea by increasing osmolarity was associated with an increased rate of blinking.…”