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Neuropathic Pain and Itch Mechanisms Underlying Allergic Conjunctivitis

Kuruvilla Merin1, Kalangara J2, Eun-Hyung Lee F3

1Assistant Professor, Allergy/Immunology, Emory University
2Assistant Professor, Interventional Pain Management, Emory University
3Associate Professor, Pulmonology, Emory University

J Investig Allergol Clin Immunol 2019; Vol. 29(5)
doi: 10.18176/jiaci.0320

Objective: Among the symptom constellation that characterizes allergic conjunctivitis, many such as burning and stinging can be attributed to chronic neuropathic pain. There is accumulating data to support that these hallmark symptoms might be linked to the effects of allergen induced neuromodulation. This review will emphasize the key characteristics of neuropathic itch and pain in allergic conjunctivitis and its pathologic mechanisms.
Methods: A literature review was conducted using a PubMed search focusing on allergic conjunctivitis, allergic conjunctivitis, neurogenic inflammation, neuropathic itch, neuropathic pain. Articles were reviewed and those discussing clinical course, pathophysiology, and neuronal regulation of chronic neuropathic symptoms as related to allergic disease were summarized.
Results: Recent evidence suggests that some symptoms of allergic conjunctivitis may be better represented as a chronic neuropathic disorder. We found that neurogenic mechanisms may have a significant role in chronic ocular surface inflammation from allergic inflammation. Manifestations may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic transition associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain.
Conclusion: Current management goals of allergic conjunctivitis aim to minimize the inflammatory cascade associated with allergic response in the initial stages of the pathological mechanism. Based on the mechanistic data reviewed herein, the recognition that neuronal inflammation explains many of the symptoms in allergic conjunctivitis opens new frontiers for drug discovery. 

Key words: Allergic Conjunctivitis, Neuropathic Pain,Neuronal Dysfunction, Dry Eye, Sensitization, Transient Receptor Potential Vanilloid 1 (TRPV1), Transient Receptor Potential Ankyrin 1 (TRPA1), Substance P (SP), Nerve Growth Factor (NGF)