A histamine-independent itch pathway is required for allergic ocular itch

Huang, Cheng Chiu; Kim, Yu Shin; Olson, William; Li, Fengxian; Guo, Changxiong; Luo, Wenqin; Huang, Andrew J.W.; Qin, Liu

doi:10.1016/j.jaci.2015.08.047

Cited by 28 publications

(34 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, TRPV1, as a nociceptive channel, is a more promising drug target than TRPM8 for treating cold allodynia. Our previous studies have shown that antagonizing TRPV1 could effectively block histamine-dependent itch in allergic conjunctivitis 30 , suggesting a potentially wide use of TRPV1 antagonists in alleviating ocular discomforts associated with different ocular conditions. Furthermore, the activation of TRPM8 + /TRPV1 + neurons by cold causes the release of substance P, which has been shown to mediate neurogenic inflammation 31,32 .…”

Section: Discussionmentioning

confidence: 99%

TRPV1 activity and substance P release are required for corneal cold nociception

Yang

Jiang

et al. 2019

Nat Commun

Self Cite

View full text Add to dashboard Cite

As a protective mechanism, the cornea is sensitive to noxious stimuli. Here, we show that in mice, a high proportion of corneal TRPM8+ cold-sensing fibers express the heat-sensitive TRPV1 channel. Despite its insensitivity to cold, TRPV1 enhances membrane potential changes and electrical firing of TRPM8+ neurons in response to cold stimulation. This elevated neuronal excitability leads to augmented ocular cold nociception in mice. In a model of dry eye disease, the expression of TRPV1 in TRPM8+ cold-sensing fibers is increased, and results in severe cold allodynia. Overexpression of TRPV1 in TRPM8+ sensory neurons leads to cold allodynia in both corneal and non-corneal tissues without affecting their thermal sensitivity. TRPV1-dependent neuronal sensitization facilitates the release of the neuropeptide substance P from TRPM8+ cold-sensing neurons to signal nociception in response to cold. Our study identifies a mechanism underlying corneal cold nociception and suggests a potential target for the treatment of ocular pain.

show abstract

Section: Discussionmentioning

confidence: 99%

TRPV1 activity and substance P release are required for corneal cold nociception

Yang

Jiang

et al. 2019

Nat Commun

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our previous study has revealed an essential involvement of TRPA1-mediated nonhistaminergic itch pathway in allergic ocular itch 18 . However, TRPA1 is expressed by both nociceptive and itch-sensing neurons 19,20 .…”

Section: Introductionmentioning

confidence: 93%

Anatomical and functional dichotomy of ocular itch and pain

Huang

Yang

Guo

et al. 2018

Nat Med

Self Cite

View full text Add to dashboard Cite

Itch and pain are refractory symptoms of many ocular conditions. Ocular itch is generated mainly in the conjunctiva and is absent from the cornea. In contrast, most ocular pain arises from the cornea. However, the underlying mechanisms remain unknown. Using genetic axonal tracing approaches, we discover distinct sensory innervation patterns between the conjunctiva and cornea. Further genetic and functional analyses in rodent models show that a subset of conjunctival-selective sensory fibers marked by MrgprA3 expression, rather than corneal sensory fibers, mediates ocular itch. Importantly, the actions of both histamine and nonhistamine pruritogens converge onto this unique subset of conjunctiva sensory fibers and enable them to play a key role in mediating itch associated with allergic conjunctivitis. This is distinct from skin itch, in which discrete populations of sensory neurons cooperate to carry itch. Finally, we provide proof of concept that selective silencing of conjunctiva itch-sensing fibers by pruritogen-mediated entry of sodium channel blocker QX-314 is a feasible therapeutic strategy to treat ocular itch in mice. Itch-sensing fibers also innervate the human conjunctiva and allow pharmacological silencing using QX-314. Our results cast new light on the neural mechanisms of ocular itch and open a new avenue for developing therapeutic strategies.

show abstract

“…While histamine has known involvement in AC itch, an additional histamine-independent mode of itch induction has recently been elucidated 17 . In a murine model, Huang et al 18 demonstrated that both TRPV1, a histamine-sensitive ion channel, and TRPA1, a histamine-independent ion channel are required for the induction of allergic ocular itch. This finding may explain the limitations of currently available anti-allergy eye drops 19 .…”

Section: Discussionmentioning

confidence: 99%

The prevalence and characteristics of chronic ocular itch: a cross-sectional survey

Stull¹,

Valdés‐Rodríguez²,

Shafer

et al. 2017

Itch

View full text Add to dashboard Cite

Introduction:In this cross-sectional study, we aimed to determine the prevalence and characteristics of chronic ocular itch in an outpatient ophthalmology and optometry clinic.Methods:Four hundred patients from an outpatient ophthalmology and optometry clinic were enrolled. The presence and characteristics of chronic ocular itch were assessed by a questionnaire. Data regarding ophthalmologic, dermatologic, and systemic conditions as well as current medications were extracted from medical records.Results:Chronic ocular itch was present in 118 (29.5%) of 400 participants. Chronic ocular pruritus was significantly more prevalent in females [P=0.015; odds ratio (OR)=1.8; 95% confidence interval (CI), 1.1–2.8] and was significantly associated with the presence of allergic conjunctivitis [51.8% (n=45); P<0.001; OR=5.0; 95% CI, 3.0–8.3], dry eye syndrome [40.1% (75); P<0.001; OR=2.6; 95% CI, 1.7–4.1], blepharitis [43.8% (n=21); P=0.021; OR=2.0; 95% CI, 1.1–3.8], and atopic dermatitis [50.0% (n=10); P=0.023; OR=2.6; 95% CI, 1.1–5.8]. Chronic ocular itch was not significantly associated with systemic conditions, or the use of prescribed ophthalmologic medications.Discussion:Chronic ocular itch is common and may be related to ophthalmologic or dermatologic pathologies. The present findings highlight the importance of identifying and managing this uncomfortable symptom that may negatively impact the quality of life and sleep of affected patients.

show abstract

A histamine-independent itch pathway is required for allergic ocular itch

Abstract: Non-histaminergic TRPA1 neural pathway is required for the development of allergic ocular itch. Pharmacological inhibition of TRPA1 channel can lead to novel therapeutic strategies to treat ocular itch in severe allergic conjunctivitis.

Cited by 28 publications

References 14 publications

TRPV1 activity and substance P release are required for corneal cold nociception

TRPV1 activity and substance P release are required for corneal cold nociception

Anatomical and functional dichotomy of ocular itch and pain

The prevalence and characteristics of chronic ocular itch: a cross-sectional survey

Contact Info

Product

Resources

About