Bright light activates a trigeminal nociceptive pathway

Abstract

Bright light can cause ocular discomfort and/or pain; however, the mechanism linking luminance to trigeminal nerve activity is not known. In this study we identify a novel reflex circuit necessary for bright light to excite nociceptive neurons in superficial laminae of trigeminal subnucleus caudalis (Vc/C1). Vc/C1 neurons encoded light intensity and displayed a long delay (>10s) for activation. Microinjection of lidocaine into the eye or trigeminal root ganglion (TRG) inhibited light responses completely, whereas topical application onto the ocular surface had no effect. These findings indicated that light-evoked Vc/C1 activity was mediated by an intraocular mechanism and transmission through the TRG. Disrupting local vasomotor activity by intraocular microinjection of the vasoconstrictive agents, norepinephrine or phenylephrine, blocked light-evoked neural activity, whereas ocular surface or intra-TRG microinjection of norepinephrine had no effect. Pupillary muscle activity did not contribute since light-evoked responses were not altered by atropine. Microinjection of lidocaine into the superior salivatory nucleus diminished light-evoked Vc/C1 activity and lacrimation suggesting that increased parasympathetic outflow was critical for light-evoked responses. The reflex circuit also required input through accessory visual pathways since both Vc/C1 activity and lacrimation were prevented by local blockade of the olivary pretectal nucleus. These findings support the hypothesis that bright light activates trigeminal nerve activity through an intraocular mechanism driven by a luminance-responsive circuit and increased parasympathetic outflow to the eye.

Figure 1

Trigeminal neurons in superficial laminae at the Vc/C1 region encode luminosity. Light stimuli were presented for 30 s duration at 20 min intervals at low, moderate and high intensity (0.5×10⁴, 1×10⁴, 2×10⁴ lux, respectively). a. Light-evoked peristimulus time histograms for neurons classified as cornea/conjunctiva (CC, upper panel) or conjunctiva only (CJ, lower panel) units. b. Summary of the response magnitude (Rmag) for CC and CJ units. c. Summary of the response duration to light. Note the greater Rmag and response duration to light for CC compared to CJ units. d. Response latency decreases similarly with increasing light intensity for CC and CJ units. *P < 0.05, **P < 0.01 versus response to low intensity light; b = P < 0.01 versus CJ units.

Figure 2

Light-evoked Vc/C1 activity requires input through the trigeminal ganglion. Intra-TRG (open circles) or intravitreal (ivt, solid squares) injection of lidocaine (2%, 1 μl) blocks completely the responses to high intensity light, whereas application to the ocular surface (open triangles) has no effect. **P < 0.01 versus pre-lidocaine value. b = P < 0.01 versus other groups.

Figure 3

An intraocular adrenergic mechanism contributes to light-evoked Vc/C1 activity. a. Peristimulus time histograms before (upper panel) and after (lower panel) ivt injection of norepinephrine (NE, 10 mM, 1 μl) on the responses to light of a CC neuron. b. Ivt injection of adrenergic agents inhibits light-evoked responses. High dose norepinephrine (upper panel, 10mM, 1 μl) or phenylephrine (lower panel, 10 mM, 1 μl) markedly inhibits the responses to moderate and high intensity light. *P < 0.05, **P < 0.01 versus response to low intensity light; b = P < 0.01 versus pre-drug value.

Figure 4

The superior salivatory nucleus (SSN) is critical for light-evoked responses by Vc/C1 neurons. a. Ipsilateral SSN injection of lidocaine (2%, 100 nl) blocks the Rmag to high intensity light stimulation. **P < 0.01 versus 0 min; b = P < 0.01 versus artificial CSF (aCSF) injected group. b. Lidocaine (solid circles) and vehicle (open circles) injection sites in SSN. Off-target injections of lidocaine are represented by open triangles. c. Light-evoked increase in tear volume is prevented by lidocaine blockade of the ipsilateral SSN. **P < 0.01 versus spontaneous tear value; b = P < 0.01 versus contralateral side; ††P < 0.01 versus light evoked tears at 0 min. d. Lidocaine injection sites in SSN ipsilateral to light stimulus and tear sample. e. Ipsilateral SSN injection of DL-homocysteine (DLH, 50 mM, 100 nl) increases the activity of light-responsive Vc/C1 neurons. **P < 0.01 versus 0 min; a = P < 0.05, b = P < 0.01 versus vehicle (aCSF) injected group. f. DLH injection sites in SSN. Abbreviations: SPVO, spinal trigeminal nucleus oralis; SSN, superior salivatory nucleus; VII, facial nucleus.

Figure 5

Inhibition of the olivary pretectal nucleus (OPN) prevents light-evoked Vc/C1 neural activity. a. Bilateral injection of lidocaine (2%, 100 nl) into the OPN blocks completely the Rmag to high intensity light stimulation. *P < 0.05, **P < 0.01 versus 0 min; a = P < 0.05, b = P < 0.01 versus vehicle (aCSF) group. b. Light-induced tear formation is prevented by OPN blockade. **P < 0.01 versus spontaneous tear value; a = P < 0.05, b = P < 0.01 versus contralateral side; † P< 0.05, ††P < 0.01 versus evoked tears at 0 min. c. Injection sites in OPN: solid circles = units, lidocaine injection; open circles = units, vehicle injection; solid triangles = tear volume, lidocaine injection. Off-target injections of lidocaine are represented by open triangles. d. An example of a OPN lidocaine injection site (asterisk). Abbreviations: APN, anterior pretectal nucleus; NOT, nucleus optic tract; OPN, olivary pretectal nucleus; PPN, posterior pretectal nucleus.

Figure 6

The proposed model for light-induced activation of trigeminal neurons involves transduction of luminance in the eye and a relay of this information to the OPN. OPN activation results in increased parasympathetic outflow to the eye through the SSN. TRG neurons could be activated by transmitters released from parasympathetic postganglionic neurons or, for those fibers apposed to blood vessels, by mechanical deformation of ocular blood vessels due to changes in blood flow. Abbreviations. OPN, Olivary pretectal nucleus; SSN, Superior salivatory nucleus; PPG, Pterygopalatine ganglion; TRG, Trigeminal root ganglion.