Abstract
The trigeminal nerve gives rise to the corneal nerve system, which plays a crucial role in sensory processing on the ocular surface (touch, pain, and temperature) as well as in healing and homeostasis through release of neuromodulators. Several forms of noxious stimuli can lead to dysfunctions along this pathway, manifesting as disease states such as dry eye disease (DED) characterized by chronic unpleasant ocular symptoms, including pain, discomfort, and photophobia. Ocular pain is part of a multidimensional sensory and emotional experience mediated by complex peripheral and central pathogenetic mechanisms. Different forms of ocular pain exist, including pain due to chronic noxious stimulation at the ocular surface (e.g., nociceptive pain), pain due to corneal nerve dysfunction causing hyperexcitability and sensitizing mechanisms (neuropathic pain), or both. Typically, noxious stimuli activate peripheral nerve terminals and generate signals that are relayed and processed in the spinal trigeminal nucleus of the medulla and then conveyed to the thalamus and other subcortical and cortical areas of the central nervous system. Normally, with removal of the stimulus, pain dissipates in an acute fashion. However, peripheral and central sensitization of neurons (due to spatially and temporally excessive noxious signal traffic, neuroinflammation, and glial activation) can result in hyperexcitability, allowing for chronicity with heightened spontaneous pain and abnormally painful evoked responses to stimuli (allodynia, hyperalgesia, photophobia). This chapter discusses concepts of corneal nerve anatomy and how they relate to ascending pathways of ocular pain and photophobia in DED.