Investigative Ophthalmology & Visual Science, Vol 38, 1944-1953, Copyright © 1997 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Reduction by antiinflammatory drugs of the response of corneal sensory nerve fibers to chemical irritation

X Chen, J Gallar and C Belmonte
Departamento de Fisiologia and Instituto de Neurociencias, Universidad Miguel Hernandez, San Juan, Spain.

PURPOSE: Nonsteroidal antiinflammatory drugs (NSAIDs) have been applied topically to reduce ocular pain caused by corneal injury or anterior segment surgery. The authors investigated whether the analgesic effects of the NSAIDs diclofenac, indomethacin, and flurbiprofen and of the calcium channel antagonist diltiazem on corneal pain are mediated by a reduction of nerve activity in corneal polymodal nociceptive fibers. METHODS: Impulse activity of single A-delta and C corneal nerve fibers was recorded from the ciliary nerves of anesthetized cats. Polymodal units were identified by their response to both touching with the Cochet-Bonnet esthesiometer and to acidic stimulation with 30-second pulses of 80% or 98.5% CO2 or 60 microl of 10 mM acetic acid, applied to the corneal receptive area. Ongoing impulse activity, firing responses to CO2 or acetic acid, and mechanical threshold of single fibers were recorded before and at various times (5 to 90 minutes) after topical application of 0.1% sodium diclofenac, 0.03% sodium flurbiprofen, 0.1% indomethacin, and 0.045% diltiazem hydrochloride or of their vehicles. RESULTS: Indomethacin, diclofenac, and flurbiprofen, in decreasing order of potency, gradually reduced the mean frequency of the impulse response of corneal polymodal nerve fibers evoked by CO2 stimuli. The progressive increase of ongoing activity, observed in vehicle-treated eyes after repeated CO2 stimulation was also prevented by NSAIDs. Diltiazem also attenuated the response to CO2 for a shorter period of time and with a faster time course. The mechanical threshold of corneal polymodal fibers was not affected by treatment with any of these drugs. CONCLUSIONS: Indomethacin, diclofenac, and flurbiprofen, as well as the calcium antagonist diltiazem, diminish the responsiveness of corneal polymodal nociceptors to chemical stimuli. This appears to be caused, in part, by a direct effect of these drugs on the excitability of polymodal nerve endings, but also by an inhibition by NSAIDs of the formation of cyclooxygenase products such as prostaglandins, thus reducing the enhanced responsiveness of nociceptors caused by local release of arachidonic acid metabolites from injured cells.

This article has been cited by other articles:

				J. Gallar, M. C. Acosta, A. R. Gutierrez, and C. Belmonte Impulse Activity in Corneal Sensory Nerve Fibers after Photorefractive Keratectomy Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4033 - 4037. [Abstract] [Full Text] [PDF]

				A. Dogrul, S. E. Gulmez, M. S. Deveci, H. Gul, M. H. Ossipov, F. Porreca, and F. C. Tulunay The Local Antinociceptive Actions of Nonsteroidal Antiinflammatory Drugs in the Mouse Radiant Heat Tail-Flick Test Anesth. Analg., April 1, 2007; 104(4): 927 - 935. [Abstract] [Full Text] [PDF]

				M. C. Acosta, C. Luna, G. Graff, V. M. Meseguer, F. Viana, J. Gallar, and C. Belmonte Comparative Effects of the Nonsteroidal Anti-inflammatory Drug Nepafenac on Corneal Sensory Nerve Fibers Responding to Chemical Irritation Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 182 - 188. [Abstract] [Full Text] [PDF]

				M. C. Acosta, L. Berenguer-Ruiz, A. Garcia-Galvez, D. Perea-Tortosa, J. Gallar, and C. Belmonte Changes in Mechanical, Chemical, and Thermal Sensitivity of the Cornea after Topical Application of Nonsteroidal Anti-inflammatory Drugs Invest. Ophthalmol. Vis. Sci., January 1, 2005; 46(1): 282 - 286. [Abstract] [Full Text] [PDF]

				T. D. Gover, J. P. Y. Kao, and D. Weinreich Calcium Signaling in Single Peripheral Sensory Nerve Terminals J. Neurosci., June 15, 2003; 23(12): 4793 - 4797. [Abstract] [Full Text] [PDF]

				N. Voilley, J. de Weille, J. Mamet, and M. Lazdunski Nonsteroid Anti-Inflammatory Drugs Inhibit Both the Activity and the Inflammation-Induced Expression of Acid-Sensing Ion Channels in Nociceptors J. Neurosci., October 15, 2001; 21(20): 8026 - 8033. [Abstract] [Full Text] [PDF]

				P. Escoubas, J. R. De Weille, A. Lecoq, S. Diochot, R. Waldmann, G. Champigny, D. Moinier, A. Menez, and M. Lazdunski Isolation of a Tarantula Toxin Specific for a Class of Proton-gated Na+ Channels J. Biol. Chem., August 11, 2000; 275(33): 25116 - 25121. [Abstract] [Full Text] [PDF]