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Area of Science:

  • Ophthalmology
  • Neuroscience
  • Pharmacology

Background:

  • Ocular surface pain is a significant clinical issue.
  • Substance P (SP) and its receptor neurokinin 1 (NK1R) are implicated in pain signaling.
  • Understanding their role is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of SP and NK1R in ocular surface pain.
  • To evaluate the efficacy of the NK1R antagonist fosaprepitant in treating ocular pain.

Main Methods:

  • Utilized wild type (WT) and TAC1-knockout (TAC1-KO) mice.
  • Applied hypertonic saline to induce ocular surface pain.
  • Administered topical fosaprepitant, oxybuprocaine chloride, or diclofenac.
  • Quantified ocular pain using the eye wiping test.
  • Measured SP levels in tears and trigeminal ganglia (TG).
  • Assessed TAC1 mRNA expression and leukocyte infiltration in corneas.

Main Results:

  • TAC1-KO mice showed significantly reduced ocular pain.
  • Topical fosaprepitant dose-dependently reduced ocular pain in WT mice.
  • Fosaprepitant and oxybuprocaine decreased SP levels, TAC1 mRNA, and leukocyte infiltration.
  • Colocalization of NK1R and β3-tubulin was observed in corneas.

Conclusions:

  • Topical NK1R antagonist fosaprepitant effectively reduces ocular surface nociception.
  • Fosaprepitant decreases SP release and corneal leukocyte infiltration.
  • Repurposing fosaprepitant shows potential for treating ocular pain.