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 (>10 s) 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 lightevoked 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.

Migraine pathophysiology: Anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain

“…More appropriately termed photooculodynia, this type of photophobia is thought to originate from indirect activation of intraocular trigeminal nociceptors. As proposed by Okamoto et al [93], bright light causes pain in the eye through activation of a complex neuronal pathway involving the olivary pretectal nucleus, the SSN and the sphenopalatine ganglion which drives parasympathetically-controlled vasodilatation and mechanical deformation of ocular blood vessels that in turn activates trigeminal nociceptors and second-order nociceptive neurons in the SpVC. Lack of evidence for induction of vasodilatation by light in the human retina question this scenario.…”

The Relation Between Light-Induced Lacrimation and the Melanopsin-Driven Postillumination Pupil Response

“…An objective index may be useful in diagnosing and monitoring the underlying etiologies of photophobia. Some studies 2,6,7 have used light-induced lacrimation in rodent models as a surrogate measure for light sensitivity. However, to the best of our knowledge, lightinduced lacrimation has not been studied in humans.…”

“…There is a growing body of evidence 2,4,6,8,9 suggesting that melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) may play a critical role in the afferent limb for photophobia. Intrinsically photosensitive RGCs are a third subset of photoreceptors that mediate the light irradiance detection pathway that gives rise to a range of nonimage-forming photoresponses including the pupillary light reflex and circadian photoentrainment.…”

Visual Dysfunction in Combat-related Mild Traumatic Brain Injury—A Review

“…31,[33][34][35][36] Although rods and cones are the primary light transmitters of the eye, other pathways exist for light to activate the pain circuit. 37,38 Intrinsically photosensitive retinal ganglion cells were discovered in recent years and have multiple functions including pathways to pupil constriction and light avoidance. 39 Melanopsin photoreceptors of the iris in mammals can bypass the optic nerve to activate nocioceptors outside the globe.…”

“…40 Experimental studies also describe a light-induced sensitization of the trigeminal pathway independent of the central visual pathways. 35,[37][38] Bohnen showed that tolerance to light and sound was decreased in patients 6 months after mild head injury compared to control subjects and suggested that the cause was a cortical and subcortical lack of inhibitory control. 34 Abnormal responses to light conditions and nonuniform cortical excitability have been described in other brain disorders associated with photophobia such as migraines and epilepsy.…”