PMID- 32939029 OWN - NLM STAT- MEDLINE DCOM- 20201214 LR - 20231112 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Sep 16 TI - Ocular surface inflammation induces de novo expression of substance P in the trigeminal primary afferents with large cell bodies. PG - 15210 LID - 10.1038/s41598-020-72295-x [doi] LID - 15210 AB - We evaluated the changes in substance P (SP)-expressing trigeminal neurons (TNs) innervating the cornea following ocular surface inflammation. Ocular surface inflammation was induced in Sprague-Dawley rats using 0.1% benzalkonium chloride (BAK). The corneal staining score, corneal epithelial apoptosis, conjunctival goblet cells, and density of corneal subbasal nerve plexus (SNP) were assessed, and the mRNA levels of SP, interleukin (IL)-1beta, IL-6, and tumour necrosis factor-alpha were measured in corneas and ipsilateral trigeminal ganglia (TG). SP-immunoreactivity (IR) was measured in corneal intraepithelial nerves and TNs. The cell size of corneal TNs in the TG was calculated. All parameters were observed immediately (BAK group), at 1 week (1 w group), and 2 months (2 m group) after 2 weeks of BAK application. BAK caused an increase in the corneal staining score and the number of apoptotic cells, loss of conjunctival goblet cells, reduced density of corneal SNP, and upregulated expression of SP and inflammatory cytokines in both the cornea and TG in the BAK group but those changes were not observed in the 2 m group. On the other hand, SP-IR% and mean cell size of corneal TNs increased significantly in the BAK, 1 w, and 2 m groups, compared to the control. Our data suggest that following ocular surface inflammation, large-sized corneal TNs which normally do not express SP, expressed it and this phenotype switching lasted even after the inflammation disappeared. Long-lasting phenotypic switch, as well as changes in the expression level of certain molecules should be addressed in future studies on the mechanism of corneal neuropathic pain. FAU - Byun, Yong-Soo AU - Byun YS AD - Department of Ophthalmology and Visual Science, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 06591, Republic of Korea. mdbyun@catholic.ac.kr. AD - Catholic Institute of Visual Science, The Catholic University of Korea, Seoul, Republic of Korea. mdbyun@catholic.ac.kr. FAU - Mok, Jee-Won AU - Mok JW AD - CK St. Mary's Eye Center, Seoul, Republic of Korea. FAU - Chung, So-Hyang AU - Chung SH AD - Department of Ophthalmology and Visual Science, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 06591, Republic of Korea. AD - Catholic Institute of Visual Science, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Kim, Hyun-Seung AU - Kim HS AD - Department of Ophthalmology and Visual Science, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 06591, Republic of Korea. AD - Catholic Institute of Visual Science, The Catholic University of Korea, Seoul, Republic of Korea. FAU - Joo, Choun-Ki AU - Joo CK AD - CK St. Mary's Eye Center, Seoul, Republic of Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200916 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Benzalkonium Compounds) RN - 0 (IL1B protein, rat) RN - 0 (Il6 protein, rat) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) RN - 0 (Tumor Necrosis Factor-alpha) RN - 33507-63-0 (Substance P) SB - IM MH - Animals MH - Apoptosis MH - Benzalkonium Compounds/*adverse effects MH - Cell Body/metabolism MH - Conjunctivitis/chemically induced/*genetics/metabolism MH - Disease Models, Animal MH - Epithelium, Corneal/cytology/drug effects/metabolism MH - Goblet Cells/cytology/drug effects/metabolism MH - Interleukin-1beta/genetics MH - Interleukin-6/genetics MH - Keratitis/chemically induced/*genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Substance P/*genetics/metabolism MH - Trigeminal Ganglion/*metabolism MH - Tumor Necrosis Factor-alpha/genetics PMC - PMC7494893 COIS- The authors declare no competing interests. EDAT- 2020/09/18 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/09/16 CRDT- 2020/09/17 05:41 PHST- 2020/05/12 00:00 [received] PHST- 2020/08/26 00:00 [accepted] PHST- 2020/09/17 05:41 [entrez] PHST- 2020/09/18 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/09/16 00:00 [pmc-release] AID - 10.1038/s41598-020-72295-x [pii] AID - 72295 [pii] AID - 10.1038/s41598-020-72295-x [doi] PST - epublish SO - Sci Rep. 2020 Sep 16;10(1):15210. doi: 10.1038/s41598-020-72295-x.