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Updated: Jun 28, 2026
Long-term Sensory Conflict in Freely Behaving Mice
Published on: February 20, 2019
CXCL10 knockdown attenuates vestibular migraine in rats by inhibiting PI3K-mediated neuroinflammation and central
Mao-Mei Song1,2, Gianluca Coppola3, Ying-Jie Gao2
1Department of Neurology, Headache Center, Shenzhen Baoan People's Hospital, The Second Affiliated Hospital of Shenzhen University, No. 118, Longjing Er Road, Shenzhen, 518000, China.
Background:
Vestibular migraine (VM) is characterized by recurrent episodes of headache and vertigo, and its pathogenesis is closely associated with neuroinflammation and central sensitization. C-X-C motif chemokine ligand 10 (CXCL10) plays a critical role in neuroinflammation and pain modulation; however, its specific involvement in VM remains unclear.
Methods:
A rat model of VM was established by repeated intraperitoneal nitroglycerin injections combined with intratympanic kainic acid administration. To investigate the role of CXCL10, adeno-associated virus encoding CXCL10-targeted shRNA (CXCL10-shRNA-AAV) was delivered intracerebroventricularly prior to model induction. A rescue experiment was further performed using the PI3K agonist 740 Y-P to reactivate PI3K/AKT signaling. Mechanical pain thresholds (hind paw and periorbital), head scratching and grooming behavior, and vestibular function scores were assessed. Expression levels of CXCL10, CXCR3, PI3K/AKT pathway components, inflammatory cytokines (pro-IL-1β, IL-6, TNF-α), and central sensitization markers (CGRP, c-fos) in the trigeminal nucleus caudalis (TNC) and vestibular nuclei (VN) were examined by Western blot, qPCR, and immunofluorescence.
Results:
VM rats exhibited hyperalgesia, vestibular dysfunction, and upregulated CXCL10 expression in both TNC and VN. Intracerebroventricular delivery of CXCL10-shRNA-AAV effectively knocked down CXCL10 expression and significantly ameliorated pain hypersensitivity and vestibular deficits. Mechanistically, CXCL10 knockdown suppressed PI3K/AKT pathway activation, reduced pro-inflammatory cytokine production (pro-IL-1β, IL-6, TNF-α), and downregulated the central sensitization markers CGRP and c-fos in both TNC and VN. Notably, reactivation of the PI3K/AKT pathway by 740 Y-P partially reversed these effects.
Conclusions:
CXCL10 contributes to VM pathophysiology by activating PI3K/AKT-mediated neuroinflammation and promoting central sensitization. Targeted knockdown of CXCL10 attenuates both pain and vestibular symptoms in a rat VM model, highlighting CXCL10 as a potential novel therapeutic target for VM.
