Neuropathic corneal pain and dry eye: a continuum of nociception

Throughout the body, damage to peripheral nerves normally involved in nociception may produce a constellation of symptoms-including irritation, itchiness and pain. The neurobiological processes involved in corneal symptoms of dry eye (DE) and neuropathic corneal pain (NCP) have not been clearly considered in terms of nociceptive processing. The conventional underlying presumption is that a labelled line principle is responsible; that these distinct perceptions are hard coded by primary afferent inputs to the central nervous system. This presumption oversimplifies the neurobiological mechanisms underlying somatosensory perception. The labelled line perspective that DE represents a chronic pain condition does not make intuitive sense: how can an eye condition that is not painful in most cases be considered a pain condition? Does not chronic pain by definition require pain to be present? On the other hand, NCP, a term that clearly denotes a painful condition, has historically seemed to resonate with clinical significance. Both DE and NCP can share similar features, yet their differentiation is not always clear. As is often the case, clinical terms arise from different disciplines, with DE evolving from ophthalmological findings and NCP inspired by pain neurophysiology. This review evaluates the current definition of these terms, the rationale for their overlap and how the neurophysiology of itch impacts our understanding of these conditions as a continuum of the same disease. Despite the complexity of nociceptive physiology, an understanding of these mechanisms will allow us a more precise therapeutic approach.