Topical Tetrodotoxin Attenuates Photophobia Induced by Corneal Injury in the Rat

  • Paul G. Green
    Department of Oral & Maxillofacial Surgery, University of California at San Francisco, San Francisco, California

    Department of Preventative & Restorative Dental Sciences, University of California at San Francisco, San Francisco, California

    Division of Neuroscience, University of California at San Francisco, San Francisco, California
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  • Pedro Alvarez
    Department of Oral & Maxillofacial Surgery, University of California at San Francisco, San Francisco, California

    Division of Neuroscience, University of California at San Francisco, San Francisco, California
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  • Jon D. Levine
    Address reprint requests to Jon D. Levine, MD, PhD, Department of Oral & Maxillofacial Surgery, University of California at San Francisco, San Francisco, CA 94143-0440.
    Department of Oral & Maxillofacial Surgery, University of California at San Francisco, San Francisco, California

    Division of Neuroscience, University of California at San Francisco, San Francisco, California

    Department of Dental Science and Medicine, University of California at San Francisco, San Francisco, California
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      • Corneal injury produced an increased sensitivity to light (photophobia).
      • Tetrodotoxin and lidocaine had no effect on light-aversive behavior in normal control rats.
      • Tetrodotoxin and lidocaine both eliminated photophobia in rats with corneal injury.
      • Because of lidocaine corneal toxicity, topical tetrodotoxin may be a safer therapeutic option.


      Corneal injury can produce photophobia, an aversive sensitivity to light. Using topical application of lidocaine, a local anesthetic, and tetrodotoxin (TTX), a selective voltage-sensitive sodium channel blocker, we assessed whether enhanced aversiveness to light induced by corneal injury in rats was caused by enhanced activity in corneal afferents. Eye closure induced by 30 seconds of exposure to bright light (460–485 nm) was increased 24 hours after corneal injury induced by de-epithelialization. Although the topical application of lidocaine did not affect the baseline eye closure response to bright light in control rats, it eliminated the enhancement of the response to the light stimulus after corneal injury (photophobia). Similarly, topical application of TTX had no effect on the eye closure response to bright light in rats with intact corneas, but it markedly attenuated photophobia in rats with corneal injury. Given the well-established corneal toxicity of local anesthetics, we suggest TTX as a therapeutic option to treat photophobia and possibly other symptoms that occur in clinical diseases that involve corneal nociceptor sensitization.


      We show that lidocaine and TTX attenuate photophobia induced by corneal injury. Although corneal toxicity limits use of local anesthetics, TTX may be a safer therapeutic option to reduce the symptom of photophobia associated with corneal injury.

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