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Bernadette O. Ibitokun, Kenneth E. Miller; CNQX Blocks Kainate-induced Corneal Irritation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1855.
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Glutamate is an excitatory neurotransmitter in the CNS. Likewise in the skin and muscle, it excites the nociceptive afferents causing sensitization. Studies have shown that glutamate along with other neurotransmitters is present in the cornea, but its role in the cornea has not been fully explored. Ionotropic glutamate receptors can be classified based on their selective agonists into NMDA, AMPA and Kainate. From previous studies in our lab, we have shown that AMPA GluR1 and GluR2/3 subunits are expressed on corneal epithelial cells and afferent nerves. We also demonstrated that they play a role in corneal nociception and blockade of this receptor reduced AMPA induced corneal irritation/pain. To determine the role of kainate in corneal nociception and to determine if increasing concentrations of CNQX (AMPA/Kainate receptor antagonist) will reduce kainate induced corneal irritation/pain.
10µl of kainic acid in 0.001, 0.033, 0.1, 0.33, 1.0, 3.3 and 10 mM concentration was topically instilled into intact rat cornea. The control animals received only the vehicle (phosphate buffered saline, pH=7.4). The number of blinking, wiping and headshaking movements were counted up to 30 seconds after instillation and compared with naïve animals and animals that received only the vehicle. In a second experiment, 10µl of a mixture of kainic acid and CNQX was topically instilled into corneas that were pretreated with CNQX. The concentration of kainic acid used was based on the least concentration that induced significant corneal irritation on the dose response study. Responses were compared with naïve animals and animals that received the vehicle.
Topical instillation of kainic acid induced significant nocifensive responses (blinking, wiping and head shaking movements) in a dose dependent fashion. CNQX reduced kainate induced nocifensive responses; P value was significant at ≤0.05.
Our data indicate that kainate receptors are involved in corneal irritation/pain and that CNQX is an effective antagonist of kainate induced corneal nociception.
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