A Novel Class of Neurons at the Trigeminal Subnucleus Interpolaris/Caudalis Transition Region Monitors Ocular Surface Fluid Status and Modulates Tear Production

Hirata, Harumitsu; Okamoto, Keiichiro; Tashiro, Akimasa; Bereiter, David A.

doi:10.1523/jneurosci.0381-04.2004

Cited by 72 publications

(70 citation statements)

References 53 publications

(78 reference statements)

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“…In contrast, drying of the ocular surface affected neurons in the Vi/Vc transition as opposed to the Vc/C 1 junction. 39 In a similar manner, the ocular sensation of itch has been postulated to also go through the Vi/Vc junction, as reviewed by Stapleton et al 34 In addition, sensory nerves also innervate the conjunctiva and eyelid margins and these nerves also likely play a role in dry eye-associated ocular pain. However, less information is available on their morphology and functions.…”

Section: Dry Eye As a Pain Disordermentioning

confidence: 98%

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

Galor

Levitt

Felix

et al. 2014

Eye

183

187

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Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eyeassociated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain.

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Section: Dry Eye As a Pain Disordermentioning

confidence: 98%

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

Galor

Levitt

Felix

et al. 2014

Eye

183

187

View full text Add to dashboard Cite

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“…[75][76][77] In contrast, there is considerable evidence that a majority of corneal HB-LT cold thermoreceptors project to second-order neurons located at the transition zone between the spinal trigeminal subnucleus caudalis and subnucleus interpolaris (Vi/Vc), an area proposed as the processing center for neural regulation of lacrimation and blinking via the superior salivatory nucleus (SSN) and the facial motor nucleus. 20,32,78 The SSN and facial motor nucleus also receive an input from Vc/C1 neurons connected to corneal nociceptors for reflex motor and autonomic ocular responses evoked by injurious stimuli. 77,79 The location in the brainstem of the second-order neurons connecting with LB-HT cold thermoreceptors is not certain.…”

Section: Sensory Nerve Terminalsmentioning

confidence: 99%

“…20,78 When there is excessive evaporation and/or hyperosmolarity of tear film, the LB-HT cold thermoreceptors may also be recruited, and evoke a sense of irritation through the same pain-labeled pathways as corneal mechano-and polymodal nociceptor nerve fibers. These three sensory receptors types may also be activated by cell shrinkage and local inflammation caused by dryness.…”

Section: Sensory Nerve Terminalsmentioning

confidence: 99%

Functional Properties of Sensory Nerve Terminals of the Mouse Cornea

González-González

Bech

Gallar

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To define the firing properties of sensory nerve terminals innervating the adult mouse cornea in response to external stimuli of differing modality.METHODS. Extracellular electrical activity of single corneal sensory nerve terminals was recorded in excised eyes of C57BL/6J mice. Eyes were placed in a recording chamber and were continuously superfused with warm saline solution. Nerve terminal impulse (NTI) activity was recorded by means of a glass pipette (tip~50 lm), applied on the corneal surface. Nerve terminal impulse discharges were stored in a computer for offline analysis.RESULTS. Three functionally distinct populations of nerve terminals were identified in the mouse cornea. Pure mechanonociceptor terminals (9.5%) responded phasically and only to mechanical stimuli. Polymodal nociceptor terminals (41.1%) were tonically activated by heat and hyperosmolal solutions (850 mOsmÁkg À1 ), mechanical force, and/or TRPV1 and TRPA1 agonists (capsaicin and allyl isothiocyanate [AITC], respectively). Cold-sensitive terminals (49.4%) responded to cooling. Approximately two-thirds of them fired continuously at 348C and responded vigorously to small temperature reductions, being classified as high-background activity, low-threshold (HB-LT) cold thermoreceptor terminals. The remaining one-third exhibited very low ongoing activity at 348C and responded weakly to intense cooling, being named low-background activity, high-threshold (LB-HT) cold thermoreceptor terminals.CONCLUSIONS. The mouse cornea is innervated by trigeminal ganglion (TG) neurons that respond to the same stimulus modalities as corneal receptors of other mammalian species. Mechano-and polymodal endings underlie detection of mechanical and chemical noxious stimuli while HB-LT and LB-HT cold thermoreceptors appear to be responsible for basal and irritation-evoked tearing and blinking, respectively.

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“…While sometimes referred to as a ''dry condition,'' neuronal discharge under this condition likely represents activity evoked by evaporative cooling and/or increased osmolarity. 15,25,26 Neuronal responses to menthol and vehicle (mineral oil) were examined by replacing artificial tears with 20 lL of the test solutions. In most experiments, vehicle and drugs were tested on the same neuron.…”

Section: Electrophysiologic Recordingsmentioning

confidence: 99%

Menthol Activation of Corneal Cool Cells Induces TRPM8-Mediated Lacrimation but Not Nociceptive Responses in Rodents

Robbins

Kurose

Winterson

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Stimulation to the cornea via noxious chemical and mechanical means evokes tearing, blinking, and pain. In contrast, mild cooling of the ocular surface has been reported to increase lacrimation via activation of corneal cool primary afferent neurons. The purpose of our study was to determine whether menthol induces corneal cool cell activity and lacrimation via the transient receptor potential melastatin-8 (TRPM8) channel without evoking nociceptive responses.METHODS. Tear measurements were made using a cotton thread in TRPM8 wild type and knockout mice after application of menthol (0.05-50 mM) to the cornea. In additional studies, nocifensive responses (eye swiping and lid closure) were quantified following cornea menthol application. Trigeminal ganglion electrophysiologic single unit recordings were performed in rats to determine the effect of low and high concentrations of menthol on corneal cool cells. RESULTS.At low concentrations, menthol increased tear production in TRPM8 wild type and heterozygous animals, but had no effect in TRPM8 knockout mice, while nocifensive responses remained unaffected. At the highest concentration, menthol (50 mM) increased tearing and nocifensive responses in TRPM8 wild type and knockout animals. A low concentration of menthol (0.1 mM) increased cool cell activity, yet a high concentration of menthol (50 mM) had no effect.CONCLUSIONS. These studies indicated that low concentrations of menthol can increase lacrimation via TRPM8 channels without evoking nocifensive behaviors. At high concentrations, menthol can induce lacrimation and nocifensive behaviors in a TRPM8 independent mechanism. The increase in lacrimation is likely due to an increase in cool cell activity. (Invest Ophthalmol Vis Sci. 2012;53:7034-7042)

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A Novel Class of Neurons at the Trigeminal Subnucleus Interpolaris/Caudalis Transition Region Monitors Ocular Surface Fluid Status and Modulates Tear Production

Cited by 72 publications

References 53 publications

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

Functional Properties of Sensory Nerve Terminals of the Mouse Cornea

Menthol Activation of Corneal Cool Cells Induces TRPM8-Mediated Lacrimation but Not Nociceptive Responses in Rodents

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