Alteration of neural activity and neuroinflammatory factors in the insular cortex of mice with corneal neuropathic pain. (8th March 2023)

• Record Type: Journal Article
• Authors: Xu, Rui; Zhang, Yu‐Wen; Gu, Qing; Yuan, Tian‐Jie; Fan, Bing‐Qian; Xia, Jun‐Ming; Wu, Jin‐Hong; Xia, Ying; Li, Wen‐Xian; Han, Yuan
• Is Part Of: Genes, brain, and behavior. Volume 22:Number 2(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-08
• Subjects: central sensitization -- corneal neuropathic pain -- dry eye disease -- insular cortex -- the amplitude of low‐frequency fluctuation; Behavior genetics -- Periodicals; Neurogenetics -- Periodicals; 616.8
• DOI: 10.1111/gbb.12842
• Languages: English
• ISSNs: 1601-1848

Abstract

Abstract: Dry eye disease (DED) affects nearly 55% of people worldwide; several studies have proposed that central sensitization and neuroinflammation may contribute to the developing corneal neuropathic pain of DED, while the underlying mechanisms of this contribution remain to be investigated. 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‐fMRI) was performed for anatomical involvement of the brain regions. The amplitude of low‐frequency fluctuation (ALFF) determined brain activity. Immunofluorescence testing and Quantitative real‐time 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 ( p < 0.01), c‐Fos ( p < 0.001), brain‐derived neurotrophic factor ( p < 0.01), TNF‐α, IL‐6, and IL‐1β ( p < 0.05). In contrast, IL‐10 levels ( p < 0.05) decreased in the dry eye group. DED‐induced corneal hypersensitivity and upregulation of inflammatory cytokines could be blocked by insular cortex injection of Tyrosine Kinase receptor B agonist cyclotraxin‐B ( p < 0.01) 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‐related corneal neuropathic pain. Abstract : The fMRI mapping showed potential brain areas involved in corneal neuropathic pain. The insular cortex is one of the brain areas affected by dry eye‐related corneal neuropathic pain and increased expressions of brain‐derived neurotrophic factor and neuroinflammation in the insular cortex may contribute to the activation of central pain pathways in corneal neuropathic pain.