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ORIGINAL RESEARCH article

Front. Neurol.
Sec. Headache and Neurogenic Pain
Volume 15 - 2024 | doi: 10.3389/fneur.2024.1468272

Acetate improves trigeminal neuralgia symptoms in mice by promoting lactate production

Provisionally accepted
Xiangbo Liu Xiangbo Liu 1Bowen Gao Bowen Gao 2Tao Qi Tao Qi 1Fei Peng Fei Peng 3*
  • 1 Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
  • 2 Chengdu Medical College, Chengdu, Sichuan, China
  • 3 Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China

The final, formatted version of the article will be published soon.

    Trigeminal neuralgia (TN) is a neuropathic pain syndrome that undesirably affects patient's quality of life. Acetate exerts extensive pathophysiological effects on the brain; however, whether acetate would improve TN symptoms as well as the underlying mechanisms remain understood. In our study, unilateral constriction of the infraorbital nerve was performed to establish a mouse model of TN.Astrocyte-specific Acss1 conditional knockout were carried out to increase brain exposure to acetate. The behavioral changes were observed and the pain thresholds were detected by Von-Frey tests at 1, 5, 10, 15 and 30 days after surgery in order to evaluate the impact of acetate on TN. Carbon 13 tracing and seahorse analysis were performed to gain more details about the impact of acetate on brain glucose metabolism. LDH knockdown in trigeminal spinal subnucleus caudalis (Sp5C) and intracerebroventricular (icv) injection of L-lactate were applied to evaluate the biological function of lactate in our model. We discovered that acetate levels in Sp5Cwere elevated for about 2.5 folds (3.63 µmol/g vs 1.43 µmol/g) after surgery and lasted for at least 30 days. This shift in acetate levels appears to be independent of peripheral circulation since plasma acetate levels remained unaltered until 30 days after surgery. Increased acetate exposure improved TN symptoms after surgery.Mechanistically, acetate-stimulated glycolysis correlated with an elevation of lactate for about 1.7 folds (29.67 µmol/g vs 18.00 µmol/g), which suppressed reactive oxygen species (ROS) production and neuroinflammation. In summary, acetate improves TN symptoms in mice by promoting lactate production in Sp5C.

    Keywords: Trigeminal Neuralgia, acetate, Lactate, ROS, Neuroinflammation

    Received: 21 Jul 2024; Accepted: 29 Aug 2024.

    Copyright: © 2024 Liu, Gao, Qi and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Fei Peng, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China

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