The cornea occupies an important place in studies of nociception because the early histology indicated exclusively free nerve endings, whereas contemporaneous psychophysical studies indicated that gentle stimulation elicited nonnociceptive responses. This challenged the dogma originating at the end of the nineteenth century that free nerve endings are associated exclusively with nociceptors and pain. Studies of the physiological properties of fibers innervating the cornea indicate the presence of polymodal nociceptive afferents with Ad- or C-fibers responding to mechanical, thermal, and chemical stimuli. The mechanical threshold of polymodal nociceptors is slightly lower than that of mechanosensory units. Thermal threshold is about 39°C. Chemical sensitivity can be demonstrated for protons, bradykinin, prostaglandin, and serotonin. A third type of unit known as a mechanoheat unit that exhibits a higher mechanical threshold than the others has also been described. Such units can develop chemical sensitivity after repeated thermal stimulation. Recent psychophysical studies of corneal sensation suggest that gentle stimulation elicits unpleasant if not frankly painful sensations, in line with the adequate stimulus of the afferent fibers innervating this tissue.

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