Neuropathic pain and dry eye

Galor, Anat; Moein, Hamid Reza; Lee, Charity; Rodríguez, Adriana; Felix, Elizabeth R.; Sarantopoulos, Konstantinos D.; Levitt, Roy C.

doi:10.1016/j.jtos.2017.10.001

Cited by 172 publications

(158 citation statements)

References 179 publications

(221 reference statements)

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“…Recently, the concept of neuropathic pain has emerged as an important factor for dry eye development, and hypersensitivity to the unstable tear film is considered the mechanism underlying dry eye. [30][31][32][33][34][35] Kaido et al 14 reported in 2016 that hypersensitivity of the cornea exists in short TBUT-type dry eye, speculating that the severe symptoms of short TBUT-type dry eye may be due to the neuropathic pain components.…”

Section: History Of the Short Tbut-type Dry Eyementioning

confidence: 99%

Short Tear Film Breakup Time–Type Dry Eye

Ohta

2018

Invest. Ophthalmol. Vis. Sci.

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Measurement of tear film breakup time (TBUT) has become a standard diagnostic procedure in the dry eye clinic. Short TBUT-type dry eye is characterized by TBUT of less than 5 seconds and dry eye symptoms such as ocular fatigue or dryness; the importance of this type has recently been gaining prominence. Patients with this condition show no reduction in tear production and no staining of the ocular surface. The severity of symptoms is almost the same as in dry eye in which the ocular surface is stained with rose bengal or fluorescein. In addition to discomfort, patients suffer from decreased vision due to the unstable tear film, which can be attributed to the relative abnormality of the lipid layer, aqueous layer, and/or mucin layer. The diagnosis should be performed carefully on the basis of the patient's symptoms and the TBUT test, because the ocular surface appears normal and remains unstained.

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Section: History Of the Short Tbut-type Dry Eyementioning

confidence: 99%

Short Tear Film Breakup Time–Type Dry Eye

Ohta

2018

Invest. Ophthalmol. Vis. Sci.

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“…[1,8,9], can lead to local release of inflammatory mediators, including calcitonin gene-related peptide (CGRP), causing corneal inflammation [10]. Stimulation of corneal nerves following damage can result in ocular pain, either to normally non-noxious stimuli (allodynia) and/or as a heightened pain response to noxious stimuli (hyperalgesia) [9,[11][12][13], which can result in sensitization and neuropathic pain over time [14].…”

Section: Introductionmentioning

confidence: 99%

“…Current pharmacotherapies for corneal pain and inflammation include topical steroids, non-steroidal anti-inflammatory drugs, antibiotics, as well as other agents for neuropathic pain including, tricyclic antidepressants, GABAergic drugs (e.g., gabapentin), opioids, etc. [12,15,16]. However, these treatments are not always effective enough to produce adequate pain relief, especially where both pain and inflammation may need to be controlled [13,15,17].…”

Section: Introductionmentioning

confidence: 99%

Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation

et al. 2020

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Cannabinoid receptor 1 (CB1) activation has been reported to reduce transient receptor potential cation channel subfamily V member 1 (TRPV1)-induced inflammatory responses and is anti-nociceptive and anti-inflammatory in corneal injury. We examined whether allosteric ligands, can modulate CB1 signaling to reduce pain and inflammation in corneal hyperalgesia. Corneal hyperalgesia was generated by chemical cauterization of cornea in wildtype and CB2 knockout (CB2−/−) mice. The novel racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229 were examined alone or in combination with the orthosteric CB1 agonist Δ8-tetrahydrocannabinol (Δ8-THC). Pain responses were assessed following capsaicin (1 µM) stimulation of injured corneas at 6 h post-cauterization. Corneal neutrophil infiltration was also analyzed. GAT228, but not GAT229 or GAT211, reduced pain scores in response to capsaicin stimulation. Combination treatments of 0.5% GAT229 or 1% GAT211 with subthreshold Δ8-THC (0.4%) significantly reduced pain scores following capsaicin stimulation. The anti-nociceptive effects of both GAT229 and GAT228 were blocked with CB1 antagonist AM251, but remained unaffected in CB2−/− mice. Two percent GAT228, or the combination of 0.2% Δ8-THC with 0.5% GAT229 also significantly reduced corneal inflammation. CB1 allosteric ligands could offer a novel approach for treating corneal pain and inflammation.

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“…Dry eye disease (DED) is among the most common ocular diseases [61] and is associated with chronic dry eye-like pain (DELP). Several comprehensive reviews discuss the relation between DED and DELP in detail, such as Rosenthal et al and Galor et al [8,62]. Under normal physiologic conditions, the corneal surface is covered by a thin tear film, composed of a mucinous layer that originates from goblet cells in the conjunctiva, an aqueous layer superficial to the mucinous layer, and an outermost lipid layer [6].…”

Section: Ocular Disease and Ocular Painmentioning

confidence: 99%

Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options

Lafreniere

Kelly

2018

Neuronal Signaling

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Challenges in the management of ocular pain are an underappreciated topic. Currently available therapeutics lack both efficacy and clear guidelines for their use, with many also possessing unacceptable side effects. Promising novel agents would offer analgesic, anti-inflammatory, and possibly neuroprotective actions; have favorable ocular safety profiles; and show potential in managing neuropathic pain. Growing evidence supports a link between the endocannabinoid system (ECS) and a range of physiological and disease processes, notably those involving inflammation and pain. Both preclinical and clinical data suggest analgesic and anti-inflammatory actions of cannabinoids and ECS-modifying drugs in chronic pain conditions, including those of neuropathic origin. This review will examine existing evidence for the anatomical and physiological basis of ocular pain, specifically, ocular surface disease and the development of chronic ocular pain. The mechanism of action, efficacy, and limitations of currently available treatments will be discussed, and current knowledge related to ECS-modulation of ocular pain and inflammatory disease will be summarized. A perspective will be provided on the future directions of ECS research in terms of developing cannabinoid therapeutics for ocular pain.

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Neuropathic pain and dry eye

Cited by 172 publications

References 179 publications

Short Tear Film Breakup Time–Type Dry Eye

Short Tear Film Breakup Time–Type Dry Eye

Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation

Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options

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