Lactate alleviates trigeminal neuralgia symptoms in mice by suppressing neuroinflammation

Objectives Trigeminal neuralgia is a neuropathic pain syndrome that undesirably affects patient’s quality of life. Lactate exerts extensive pathophysiological effects on the brain; however, it remains unclear whether lactate improves trigeminal neuralgia symptoms as well as the underlying mechanisms. Methods In our study, unilateral constriction of the infraorbital nerve was performed to establish a mouse model of trigeminal neuralgia. Conditional knockout of the astrocyte-specific lactate dehydrogenase gene was performed to decrease brain exposure to lactate. The behavioral changes were observed and the pain thresholds were detected via von Frey tests at 1, 5, 10, 15, and 30 days after surgery to evaluate the impact of lactate on trigeminal neuralgia. Intracerebroventricular injection of L-lactate was administered to evaluate the biological function of lactate in our model. Results We revealed that lactate levels in the spinal trigeminal nucleus were elevated by approximately 2.5-fold (3.63 vs. 1.43 µmol/g) after surgery, which remained elevated for at least 30 days. This shift in lactate levels appeared to be independent of peripheral circulation, as plasma lactate levels remained unaltered until 30 days after surgery. Increased lactate exposure alleviated trigeminal neuralgia symptoms after the surgery. Mechanistically, lactate suppressed reactive oxygen species production and neuroinflammation. Conclusions Lactate may alleviate trigeminal neuralgia symptoms in mice by suppressing neuroinflammation.