Sensory experiences in humans and single-unit activity in cats evoked by polymodal stimulation of the cornea

Abstract

1. The cornea of human subjects and of anaesthetised cats was stimulated with a jet of air of controlled flow, temperature and CO(2) concentration delivered by a gas aesthesiometer. 2. In humans, the intensity and magnitude of various components of the sensory experience (intensity of the sensation, degree of irritation, magnitude of burning and stinging pain, magnitude of the cold and warm components of the sensation) were measured using separate visual analog scales. In anaesthetised cats, the impulse response to the same stimuli was recorded from single mechanosensory, polymodal and cold-sensitive corneal fibres in the ciliary nerves. 3. Intensity-response curves for mechanical stimulation showed that all parameters of the sensation experienced by humans increased with the intensity of the stimulus. Mechanical stimuli recruited mainly phasic mechanosensory and polymodal afferents in the cat. 4. Acidic stimulation with gas mixtures of increasing CO(2) concentration evoked irritation, burning and to a lesser extent stinging pain of a magnitude roughly proportional to the intensity of the stimulus in humans. CO(2) primarily recruited polymodal afferents and weakly excited cold-sensitive fibres in the cat's cornea. 5. Heat stimuli evoked in humans a sensation profile similar to CO(2) but accompanied by a warmth component. In the cat's cornea, heat excited only polymodal fibres and silenced cold-sensitive corneal units. 6. Cold stimuli applied to the human cornea elicited a sensation of cooling that became irritant at the lowest temperatures. Corneal cold-sensitive fibres of the cat were activated in a manner proportional to the temperature drop, while polymodal nociceptor fibres were recruited only by the lowest temperatures. Topical menthol (0.2 mM) applied to humans evoked and later eliminated cold sensations produced by cold stimuli while the irritation sensation caused by low temperature stimuli still persisted. 7. Human subjects were able to identify masked mechanical, thermal and chemical stimuli applied to the cornea. 8. Irritation and cold sensations can therefore be evoked separately from the cornea by selective activation of mechanosensory, polymodal and cold corneal sensory afferents. Stimulation with different forms of energy usually leads to combined activation and/or inhibition of the different populations of sensory afferent fibres, evoking blended sensations that include irritation and thermal components in a variable degree.

Figure 1. Temperature change at the corneal surface during thermal stimulation

A, corneal surface temperature changes during stimulation with 3 s air jets of different temperatures (−10 to +80 °C), applied at flows below 150 ml min⁻¹, n = 6–7. The 50 °C point is the average of 32 determinations performed at variable flows (0–267 ml min⁻¹). The regression curve (y = 0.08x − 3.9; r²=0.994) was used to estimate the corneal temperature change evoked by the stimulus in the experiments in which no simultaneous thermography was performed. B, example of thermography temperature profiles in the ocular surface at the end of a stimulation with an air jet of 3 s duration, at a subthreshold flow (39 ml min⁻¹). Stimulus temperature at the tip of the probe was −10 °C in the upper and +80 °C in the lower picture. Scale bars, 10 mm. Dotted lines show the limits of the cornea.

Figure 2. Relationship between the amplitude of mechanical stimulation and VAS values in human subjects

A, intensity. B, irritation. C, stinging. D, burning. E, warming. F, cooling. Data are means ±s.e.m., n = 16 subjects.

Figure 3. Relationship between the magnitude of chemical stimulation and VAS values in human subjects

A, intensity. B, irritation. C, stinging. D, burning. E, warming. F, cooling. Data are means ±s.e.m., n = 16 subjects.

Figure 4. Relationship between the magnitude of heat stimulation and VAS values in human subjects

A, intensity. B, irritation. C, stinging. D, burning. E, warming. F, cooling. VAS data (means ±s.e.m., n = 16 subjects) are plotted against the change in corneal temperature.

Figure 5. Relationship between the magnitude of cold stimulation and VAS values in human subjects

A, intensity. B, irritation. C, stinging. D, burning. E, warming. F, cooling. Data are means ±s.e.m., n = 16 subjects.

Figure 6. Effect of 0.2 mm menthol on the VAS response to cold stimulation

A, intensity. B, irritation. C, stinging. D, burning. E, warming. F, cooling. The subject's cornea was treated with Hylashield alone (•) and Hylashield plus 0.2 mm menthol (^) prior to stimulation. Data are means ±s.e.m., n = 4 subjects. In menthol-treated subjects, the value of irritation at -4.75 °C below the basal corneal temperature was significantly different from the value at this basal corneal temperature (34.4 °C; P < 0.05, paired t test).

Figure 7. Comparison between components of the sensation evoked by different modalities of stimulation

Data are means ± s.e.m., n = 9 subjects. Values of the different components of sensation evoked by selective mechanical, chemical, heat and cold stimuli with the same mean subjective intensity (4 VAS units, see text) were compared. *P < 0.05, significant difference between the magnitudes of the sensation components signalled by the end of the vertical lines inside each modality of stimulation. **P < 0.05 significant difference between the magnitudes of the sensation component comparing all the modalities of stimulation (P < 0.05, Tukey's test after two-way RM ANOVA).

Figure 8. Correlation between VAS ratings in humans and impulse response of corneal units in cats

A, mechanical stimulation. B, cold stimulation. Data were obtained using an identical stimulation protocol for the psychophysical and the electrophysiological experiments. Pearson's correlation and linear regression (continuous lines) were statistically significant.