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Excision of extra orbital lacrimal glands established the dry eye model. Corneal hypersensitivity was examined through chemical and mechanical stimulation, and open field test measured the anxiety levels. Restingstate fMRI is a method of functional magnetic resonance imaging (rs\u2010fMRI) was performed for anatomical involvement of the brain regions. The amplitude of low\u2010frequency fluctuation (ALFF) determined brain activity. Immunofluorescence testing and Quantitative real\u2010time polymerase chain reaction were also performed to further validate the findings. Compared with the Sham group, ALFF signals in the supplemental somatosensory area, secondary auditory cortex, agranular insular cortex, temporal association areas, and ectorhinal cortex brain areas were increased in the dry eye group. This change of ALFF in the insular cortex was linked with the increment in corneal hypersensitivity (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), c\u2010Fos (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), brain\u2010derived neurotrophic factor (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In contrast, IL\u201010 levels (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) decreased in the dry eye group. DED\u2010induced corneal hypersensitivity and upregulation of inflammatory cytokines could be blocked by insular cortex injection of Tyrosine Kinase receptor B agonist cyclotraxin\u2010B (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) without affecting anxiety levels. Our study reveals that the functional activity of the brain associated with corneal neuropathic pain and neuroinflammation in the insular cortex might contribute to dry eye\u2010related corneal neuropathic pain.<\/jats:p>","DOI":"10.1111\/gbb.12842","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T02:59:46Z","timestamp":1678330786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Alteration of neural activity and neuroinflammatory factors in the insular cortex of mice with corneal neuropathic pain"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7001-3531","authenticated-orcid":false,"given":"Rui","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Eye and ENT Hospital, Fudan University  Shanghai 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