Brain Function Activity Changes and Contribution of Neuroinflammatory
Factors in Insular Cortex of Mice with Dry Eye-Related Chronic Corneal
Pain.
Abstract
Purpose:Chronic corneal pain is the most common symptom of dry eye
disease (DED), while the central sensitization mechanisms underlying
remain unclear. Methods:Excision of extra orbital lacrimal glands was
used to establish dry eye (DE) model. Tear volume measurements, corneal
fluorescein staining, corneal hypersensitivity and anxiety behavior were
tested after surgery. The amplitude of low-frequency fluctuation (ALFF)
by fMRI was used for determining brain functional activity. C-Fos,
Brain-derived neurotrophic factor (BDNF), and cytokine levels in
corresponding brain regions were tested. Results:Compared to the Sham
group, the ALFF signals in the supplemental somatosensory area,
secondary auditory cortex, agranular insular cortex, temporal
association areas, and ectorhinal cortex brain areas were enhanced in DE
group. ALFF signal in the insular cortex was related to corneal
hypersensitivity (p < 0.01). C-Fos (P < 0.001), BDNF
(P < 0.01), TNF-α, IL-6 and IL-1β (P < 0.05)
increased, while IL-10 levels (P < 0.05) decreased in the
insular cortex in the DE group. Surgery-induced corneal hypersensitivity
and upregulation of inflammatory cytokines, but not anxiety, could be
blocked by insular cortex injection of Tyrosine Kinase receptor B (TrkB)
agonist cyclotraxin-B (P< 0.01). Conclusions :This research
presents the map of functional brain by ALFF through rs-fMRI associated
with chronic corneal pain. BDNF-TrkB signaling-related neuroinflammation
in the insular cortex might contribute to dry eye-related chronic
corneal pain. This measure could potentially help clinicians improve
therapeutic approach to pain control and development of diagnostic
approach.