Calcitonin gene-related peptide and persistent corneal pain: A trigeminal nerve sensitization perspective

Persistent corneal pain (PCP) has excellent research prospects, especially the central sensitization mechanism of the trigeminal nerve, which is involved in migraine, corneal pain, and trigeminal neuralgia. The cornea has dense sensory innervation, and repeated corneal neuropathic pain has been associated with trigeminal nerve central sensitization, which is induced in PCP. The calcitonin gene-related peptide (CGRP) is involved in corneal pain conduction, injury protection, and immune homeostasis. A high CGRP level maintains corneal pain perception and protects corneal epithelial cells. However, a persistently high CGRP level causes hypersensitivity of the corneal and trigeminal nerves, resulting in PCP. CGRP-related drugs can effectively improve trigeminal nerve sensitization and relieve central sensitization-related pain (PCP, migraine, and trigeminal neuralgia). Exploring the role of CGRP in PCP's pain sensitization mechanism is vital in the pain perception field, with the potential to improve the quality of life of patients with PCP and strengthen the understanding of CGRP's dual role in corneal pain.