Topical Tetrodotoxin Attenuates Photophobia Induced by Corneal Injury in the Rat

Green, Paul G.; Álvarez, Pedro; Levine, Jon D.

doi:10.1016/j.jpain.2015.06.002

Cited by 13 publications

(20 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Responses in both eyes were at baseline levels one week after injury ( Fig.1). The presence of hyperalgesia in the abraded eye is consistent with prior studies of increased photophobia using this model of corneal injury [19]. baseline levels in Abraded animals by the second day post-abrasion and remained at baseline through one…”

Section: Corneal Abrasion Causes Short-term Increase In Evoked and Spsupporting

confidence: 89%

“…We found expression of CGRP in these neuromas and others have found accumulation of sodium channels at these sites, coupled with increase excitability of injured nerves [3; 11; 12; 40]. Blockade of sodium channels with TTX prevents the photophobia seen with corneal heptanol injury [19]. Since both the light used to evoke photophobia and our topical menthol application are able to reach nerve endings at the edge of the corneal 1 6…”

Section: Discussionmentioning

confidence: 50%

“…9B) eye closures in subsets of our corneal injury rats and uninjured control rats. We were not able to accurately quantify blinking and winking behavior at 24 hours after injury because these rats exhibit profound photophobia including extended eye closures [19]. However, there were increased ipsilateral winks one week after abrasion compared to Baseline (Fig.…”

Section: Corneal Abrasion Increases Unilateral Eye Closures (Winks) Bmentioning

confidence: 99%

See 2 more Smart Citations

Acute Hyperalgesia and Delayed Dry Eye After Corneal Abrasion Injury

Hegarty

Hermes

Morgan

et al. 2018

Preprint

View full text Add to dashboard Cite

Corneal nerves mediate pain from the ocular surface, lacrimation, and blinking, all of which protect corneal surface homeostasis and help preserve vision. Corneal nerve density correlates with neuropathic pain states and is used as an assessment of small fiber neuropathies. Because pain, lacrimation and blinking are rarely assessed at the same time, it is not known if their regulatory mechanisms have similar temporal dynamics after acute corneal injury. We examined changes in corneal nerve density, evoked and spontaneous pain, and ocular homeostasis in Sprague-Dawley male rats after a superficial epithelial injury with heptanol that acutely abolished nerve endings within the central cornea. Despite a profound loss of epithelial nerve endings, pain was transiently enhanced after abrasion injury, while basal tear production was normal. We found no relationship between epithelial nerve density and pain or homeostatic responses. Axotomy following corneal abrasion increased expression of both ATF3 (a nerve injury marker) and CGRP (a nociceptive peptide) in trigeminal ganglia 24 hours after injury. These molecular changes were absent on the contralateral side, despite reductions in corneal epithelial nerve density in the uninjured eye. ATF3 and CGRP levels in trigeminal ganglion were normal at one week post-injury when pain responses were normal. In contrast, CGRP was upregulated in peripheral corneal endings one week after injury, when dry eye symptoms emerged. Our results demonstrate dynamic trafficking of CGRP within trigeminal sensory nerves, with elevations in the ganglion correlated with pain behaviors and elevations in peripheral endings correlated with dry eye symptoms. peer-reviewed)

show abstract

Section: Corneal Abrasion Causes Short-term Increase In Evoked and Spsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 50%

Section: Corneal Abrasion Increases Unilateral Eye Closures (Winks) Bmentioning

confidence: 99%

See 1 more Smart Citation

Acute Hyperalgesia and Delayed Dry Eye After Corneal Abrasion Injury

Hegarty

Hermes

Morgan

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…The second model, corneal scraping, corresponds to an axotomy of the corneal sensory axon terminals at the basal epithelial cell layer (Liang et al, 2012). In this model, we performed experiments 24 hr after nerve axotomy because the pain peaks occurred at 24 hr after epithelial debridement (Green, Alvarez, & Levine, 2015;Hegarty, Hermes, Morgan, & Aicher, 2018) and in commonly used animal models of neuropathic pain, pain behaviours appear within the first 12-48 hr after injury (Bennett & Xie, 1988;Kim & Chung, 1992;Seltzer, Dubner, & Shir, 1990). IVCM images showed the presence of numerous inflammatory cells 24 hr after corneal scraping, which is in accordance with other studies (Li, Xie, Strong, & Zhang, 2007;Li, Zhang, Xie, Strong, & Zhang, 2017).…”

Section: Discussionmentioning

confidence: 99%

Effects of corneal injury on ciliary nerve fibre activity and corneal nociception in mice: A behavioural and electrophysiological study

Joubert

Acosta

Gallar

et al. 2018

European Journal of Pain

View full text Add to dashboard Cite

Background Ocular surface diseases are among the most frequent ocular pathologies. Ocular pain following corneal injury is frequently observed in clinic. Corneal sensory innervation is supplied by ciliary nerves derived from ophthalmic division of the trigeminal ganglion. Methods & Results Extracellular activity of the mouse ciliary nerve was first used to investigate the corneal responsiveness to chemical, mechanical and thermal stimulations in order to specifically study the responses of polymodal nociceptors, mechano‐nociceptors and cold thermoreceptor in a control cornea. Then, in two models of corneal injury (repeated instillations of 0.02% benzalkonium chloride and corneal scraping), we first measured the corneal sensitivity to chemical (eye‐wiping test) and mechanical (von Frey filaments) stimulation. Thereafter, we evaluated whether these corneal injuries modified the spontaneous and chemical stimulation‐evoked activity of the ciliary nerve. Both models of injury induced a significant corneal chemical hypersensitivity correlated with an increase of the spontaneous activity of the ciliary nerve and a faster response of the ciliary nerve after a chemical stimulation. Conclusions Overall, this study provides new insights into the functional aspects of corneal nerve fibre activity in mice after corneal injury. The increase in ciliary nerve activity may thus contribute to the development of ocular pain after corneal damage. Significance This study highlights the parallel increase in ciliary nerve activity and corneal sensitivity after corneal injury in mice. The strategy of combining ex vivo electrophysiological recordings of the ciliary nerve in mice and corneal sensitivity measurements therefore helps to uncover the functional aspects of corneal pain.

show abstract

“…The cornea has the physiological capacity to absorb the majority of ultraviolet radiation (UVR), and protects the inner eye from ultraviolet (UV)-induced oxidative damaging effects (1). corneal injury can produce photophobia, an aversive sensitivity to light, and even blindness (2), and corneal injury remains a major reason for consultations in ophthalmology clinics worldwide (3). The common pathological characteristics of corneal injury include inflammatory factor activation, vascular endothelial cell or inflammatory cell infiltration into lesions, corneal edema, corneal neovascularization (cNV) and scar formation (4).…”

Section: Introductionmentioning

confidence: 99%