Ambroxol is Effective for Corneal Pain in Rats

PURPOSE: Ambroxol is a high-potency inhibitor of voltage-gated sodium channels Nav1.7 and Nav1.8 responsible for nociceptive and neuropathic pain. This study investigated the analgesic property of ambroxol on corneal pain in rats as well as its toxicity on human corneal epithelial cells. METHODS: Inhibition of corneal sensation (CS) by ambroxol hydrochloride (AH) in Sprague-Dawley rats was assessed by Cochet-Bonnet esthesiometer. Rat corneal pain was induced by administering 5 M NaCl drops to the eyes, and eye wiping rates were recorded to reflect pain intensity. Subsequently, a rat neuropathic corneal pain (NCP) model was created by first removing the corneal epithelium and then provoking pain with 2 M NaCl. The analgesic property of 0.5% AH eye drop was assessed in rats by reductions in eye wiping rates. In cultured human corneal epithelial cells, the adverse effects of AH on cell migration and viability were studied by cell scratch and Cell Counting Kit-8 tests. RESULTS: It was noted that 0.5% AH could significantly inhibit CS, and 0.5% AH is efficacious in suppressing rat corneal pain as well as heightened nociceptor sensitivity from repetitive stimulation from irritants. At concentrations up to 30 μM, AH does not affect corneal epithelial cell migration, cell proliferation, and viability. CONCLUSIONS: Selective blockage of key nociceptors of the cornea by ambroxol is effective in suppressing corneal pain and heightened nociceptor excitability, leading to modulation of NCP. Sparing certain CS could translate into more protection to the ocular surface. No overt toxicity of ambroxol was seen in cultured human corneal epithelial cells in this study.