CO2 STIMULATION OF THE CORNEA - A COMPARISON BETWEEN HUMAN SENSATION AND NERVE ACTIVITY IN POLYMODAL NOCICEPTIVE AFFERENTS OF THE CAT

Excitation of nociceptors by low pH has been proposed as a cause of pa in following tissue injury. Here we have studied the effect of pH redu ctions caused by application of CO2 pulses to the cornea on the activi ty of corneal afferent nerves of the cat and on the magnitude of pain sensations in humans. Single-unit activity was recorded from corneal a fferent fibres in anaesthetized cats. The corneal receptive field of A -delta or C polymodal nociceptive units was exposed for 30 s to a gas mixture with different concentrations of CO2 in air (0, 35, 50, 65, 80 and 98.5%). Responses to CO2 were evoked at a mean threshold concentr ation of 40 +/- 3% CO2. They consisted of a discharge of impulses that decayed gradually to a tonic level. In 15% of the units the initial b urst was absent. The CO2 concentration and firing frequency data could be fitted to a power function with an exponent of 1.12. Pulses of CO2 were also applied to the cornea of 16 human volunteers. Sensations ex perienced were measured by means of a visual analogue scale and a verb al descriptor scale. Flow was adjusted below the mechanical stimulatio n threshold (2.8 +/- 0.5 mg). When mixtures containing 10-90% CO2 in 5 % steps were applied as 3 s pulses, threshold sensation, described as a mild stinging pain, was evoked at 33.5 +/- 4.0% CO2. This sensation became overtly painful with higher CO2 concentrations (47.5 +/- 3.6% C O2). For the same subject the sensory threshold was remarkably constan t, though it changed with longer exposure times. The relationship betw een CO2 concentration and magnitude of pain could be adjusted to a pow er function with a power exponent of 1.12. Curves of CO2 concentration versus neural discharges in the cat and versus psychophysical sensati on in humans were very similar. These results show that corneal polymo dal nociceptors respond to protons, and encode changes in CO2 concentr ation presumably reflecting pH changes. The same stimulus evokes corne al pain sensations in humans, thus opening the possibility of using CO 2 as an effective stimulus for corneal aesthesiometry.