Ocular surface itch and pain: key differences and similarities between the two sensations

Abstract

Purpose of review: To review the pathophysiology and treatment of ocular itch and pain, encompassing nociceptive and neuropathic categories.

Recent findings: Ocular itch and pain are sensations that arise from activation of ocular surface polymodal nerves. Nociceptive itch, commonly comorbid with ocular pain complaints, is mainly driven by a histamine-mediated type 1 hypersensitivity reaction. Beyond topical therapy, novel drug delivery systems are being explored to improve ocular residence time of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihistamines. Nociceptive ocular pain can be driven by a variety of factors. Treatment focuses on addressing the causative sources of pain. Neuropathic ocular itch and pain are driven by nerve damage and dysfunction and as such, topical and oral neuromodulation have been explored as treatments. Oral neuromodulators include alpha 2 delta ligands, tricyclic antidepressants (TCAs), and low dose naltrexone. Novel therapies are being evaluated for both modalities such as difelikefalin (κ-opioid receptor agonist) for neuropathic itch and libvatrep (transient receptor potential vanilloid 1 antagonist) for neuropathic pain.

Summary: Both ocular itch and pain can be driven by nociceptive and/or neuropathic mechanisms. Identifying contributors to abnormal ocular sensations is vital for precise medical care. Novel therapeutics for these conditions aim to improve patient outcomes and quality of life.

Figure 1.

Understanding the Triggers and Progression of Sensory Experiences: A Flowchart of Nociceptive Itch, Neuropathic Itch/Pain, and Nociceptive Pain Figure 1 is a flowchart that provides a simplified overview of the complex sensory experiences associated with three categories: Nociceptive Itch, Neuropathic Itch/Pain, and Nociceptive Pain. Nociceptive itch is usually triggered by an external allergen, such as pollen or dust mites, which leads to a Type 1 hypersensitivity reaction. This causes mast cells to release pro-inflammatory mediators, including histamine, resulting in an inflammatory response that ultimately leads to the sensation of itch. Nociceptive pain is caused by noxious stimuli, such as acute trauma, aqueous tear deficiency, or anatomical disturbances, which lead to the depolarization of first-order afferent neurons. This ultimately sends a signal through the trigeminal nerve (V1) to the primary somatosensory cortex, resulting in the feeling of pain. Nociceptive itch and pain most often resolve when the offending insult is removed. Neuropathic itch and pain occur due to damage and/or dysregulation of the peripheral and/or central sensory nerves/pathways. Continuous release of pro-inflammatory mediators and/or persistent depolarization of the primary afferent neurons can result in neuropathic itch, pain, or both which can persist despite resolution of the initial insult.