Immunity and pain in the eye: focus on the ocular surface

Most ocular diseases are associated with pain. While pain has been generally considered a mere (deleterious) additional symptom, it is now emerging that it is a key modulator of innate/adaptive immunity. Because the cornea receives the highest nerve density of the entire body, it is an ideal site to demonstrate interactions between pain and the immune response. Indeed, most neuropeptides involved in pain generation are also potent regulators of innate and adaptive leukocyte physiology. On the other hand, most inflammatory cells can modulate the generation of ocular pain through release of specific mediators (cytokines, chemokines, growth factors, and lipid mediators). This review will discuss the reciprocal role(s) of ocular surface (and specifically: corneal) pain on the immune response of the eye. Finally, we will discuss the clinical implications of such reciprocal interactions in the context of highly prevalent corneal diseases.