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- Title
Alleviation of migraine related pain and anxiety by inhibiting calcium-stimulating AC1-dependent CGRP in the insula of adult rats.
- Authors
Li, Yang; Li, Chenhao; Chen, Qi-Yu; Hao, Shun; Mao, Jingrui; Zhang, Wenwen; Han, Xun; Dong, Zhao; Liu, Ruozhuo; Tang, Wenjing; Zhuo, Min; Yu, Shengyuan; Liu, Yinglu
- Abstract
Background: Recent animal and clinical findings consistently highlight the critical role of calcitonin gene-related peptide (CGRP) in chronic migraine (CM) and related emotional responses. CGRP antibodies and receptor antagonists have been approved for CM treatment. However, the underlying CGRP-related signaling pathways in the pain-related cortex remain poorly understood. Methods: The SD rats were used to establish the CM model by dural infusions of inflammatory soup. Periorbital mechanical thresholds were assessed using von-Frey filaments, and anxiety-like behaviors were observed via open field and elevated plus maze tests. Expression of c-Fos, CGRP and NMDA GluN2B receptors was detected using immunofluorescence and western blotting analyses. The excitatory synaptic transmission was detected by whole-cell patch-clamp recording. A human-used adenylate cyclase 1 (AC1) inhibitor, hNB001, was applied via insula stereotaxic and intraperitoneal injections in CM rats. Results: The insular cortex (IC) was activated in the migraine model rats. Glutamate-mediated excitatory transmission and NMDA GluN2B receptors in the IC were potentiated. CGRP levels in the IC significantly increased during nociceptive and anxiety-like activities. Locally applied hNB001 in the IC or intraperitoneally alleviated periorbital mechanical thresholds and anxiety behaviors in migraine rats. Furthermore, CGRP expression in the IC decreased after the hNB001 application. Conclusions: Our study indicated that AC1-dependent IC plasticity contributes to migraine and AC1 may be a promising target for treating migraine in the future.
- Subjects
MIGRAINE prevention; ANXIETY prevention; ENZYME inhibitors; BIOLOGICAL models; CHRONIC pain; INTRAPERITONEAL injections; INSULAR cortex; RESEARCH funding; TREATMENT effectiveness; DESCRIPTIVE statistics; FLUORESCENT antibody technique; NEURAL transmission; CELLULAR signal transduction; RATS; CALCIUM; NEUROPEPTIDES; ANIMAL experimentation; WESTERN immunoblotting; PAIN management; COMPARATIVE studies; CELL receptors; EVALUATION
- Publication
Journal of Headache & Pain, 2024, Vol 25, Issue 1, p1
- ISSN
1129-2369
- Publication type
Article
- DOI
10.1186/s10194-024-01778-3