2. Academic Validation
  3. Caveolin-1 is essential for the increased release of glutamate in the anterior cingulate cortex in neuropathic pain mice

Caveolin-1 is essential for the increased release of glutamate in the anterior cingulate cortex in neuropathic pain mice

  • J Neuropathol Exp Neurol. 2023 Jul 21;nlad056. doi: 10.1093/jnen/nlad056.
Jun-Xia Yang 1 2 3,  Wei-Nan Zhao 1 2 3,  Yan-Yu Jiang 1 2,  Yu Ma 1 2 3,  Dan-Dan Chen 1 2 3,  Zhi-Hua Lin 1 2 3,  Meng-Bing Yin 1 2 3,  Kun-Peng Ren 1 2 3
Affiliations

Affiliations

  • 1 Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, China.
  • 2 Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, China.
  • 3 NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, China.
PMID: 37478479 DOI: 10.1093/jnen/nlad056
Abstract

Neuropathic pain has a complex pathogenesis. Here, we examined the role of caveolin-1 (Cav-1) in the anterior cingulate cortex (ACC) in a chronic constriction injury (CCI) mouse model for the enhancement of presynaptic glutamate release in chronic neuropathic pain. Cav-1 was localized in glutamatergic neurons and showed higher expression in the ACC of CCI versus sham mice. Moreover, the release of glutamate from the ACC of the CCI mice was greater than that of the sham mice. Inhibition of Cav-1 by siRNAs greatly reduced the release of glutamate of ACC, while its overexpression (induced by injecting Lenti-Cav-1) reversed this process. The chemogenetics method was then used to activate or inhibit glutamatergic neurons in the ACC area. After 21 days of injection of AAV-hM3Dq in the sham mice, the release of glutamate was increased, the paw withdrawal latency was shortened, and expression of Cav-1 in the ACC was upregulated after intraperitoneal injection of 2 mg/kg clozapine N-oxide. Injection of AAV-hM4Di in the ACC of CCI mice led to the opposite effects. Furthermore, decreasing Cav-1 in the ACC in sham mice injected with rAAV-hM3DGq did not increase glutamate release. These findings suggest that Cav-1 in the ACC is essential for enhancing glutamate release in neuropathic pain.

Keywords

Anterior cingulate cortex; Caveolin-1; Glutamate release; Neuropathic pain.

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