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=5k-20klux) 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.

Keywords: corneal reflex; electromyography; ocular pain; orbicularis oculi; synaptic blocked; trigeminal brainstem.

Conflict of interest statement

The authors have no financial or other relationship to report that might lead to a conflict interest.

Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Figures

Figure 1

Measurement of OOemg activity in response to hypertonic saline solutions applied to the ocular surface. A. Examples of OOemg activity after 0.15, 2.5 and 5 M NaCl. Arrow indicates stimulus onset. NaCl solutions were flushed from the surface by artificial tears after each presentation. B. Magnitude of the OOemg response, defined as the integrated area over a 3 min sampling period minus background activity, to hypertonic saline. C. Response latency to hypertonic saline. n = 6; **p

Figure 2

Measurement of the OOemg response to bright light. A. Examples of OOemg activity after high intensity light (20k lux) applied for 30 s or 60 s. B. Magnitude of the OOemg response, defined as the integrated area over a 3 min sampling period minus background activity, to light stimulation at low (5k lux), moderate (10k lux) and high intensity (20k lux). C. Response latency to light. 30 s duration, n = 7; 60 s duration, n = 5; *p

Figure 3

Effect of lidocaine applied to the ocular surface (OS) or microinjected into the trigeminal ganglion (TG) on evoked OOemg activity. A. Lidocaine blockade of OS or within TG greatly reduced the OOemg response to 2.5 M NaCl. Note that evoked OOemg activity returned to pre-drug levels by 30 min after lidocaine. B. Lidocaine blockade within TG prevented the OOemg response to light (20k lux, 60s duration), while lidocaine applied to the OS had no effect. C. Sites of drug injections into TG. n = 4 per treatment group; **p

Figure 4

Effect of synaptic blockade at the Vi/Vc transition or the Vc/C1 region on the OOemg response to 2.5 M NaCl applied to the ocular surface. A. Microinjection of CoCl2 (100 mM, 0.3 μl) into the Vi/Vc transition reduced the response to 2.5 M NaCl. B. Microinjection of CoCl2 (100 mM, 0.3 μl) into the Vc/C1 region reduced the response to 2.5 M NaCl. C. Sites of drug injections into the Vi/Vc transition (top) and Vc/C1 region (bottom). n = 4 per treatment group; *p<0.05, **p<0.01 versus pre-drug response; a = p<0.05, b = p<0.01 versus response after vehicle injections.

Figure 5

Effect of synaptic blockade at the Vi/Vc transition or Vc/C1 region on the OOemg response to bright light (20k lux, 60 s duration). A. Microinjection of CoCl2 (100 mM, 0.3 μl) into the Vi/Vc transition prevented the response to light. B. Microinjection of CoCl2 (100 mM, 0.3 μl) into the Vc/C1 region prevented the response to light. n = 4 per treatment group; **p<0.01 versus pre-drug response; a = p<0.05, b = p<0.01 versus response after vehicle injections.