Artesunate alleviates post-central stroke pain by inhibiting metabotropic glutamate receptor 5 in the cerebral cortex in rats.

Abstract

Central post-stroke pain (CPSP) is a frequent complication following a stroke, significantly reducing the quality of life for stroke patients. The cause of CPSP remains unclear; consequently, effective treatment options are limited. Central neuronal hyperexcitability is a significant contributor to CPSP pathogenesis. Artesunate (Arte) reduces neuronal hyperexcitability by inhibiting mGluR5 expression. This study aimed to investigate whether artesunate could reduce CPSP by inhibiting mGluR5 expression. A thalamic hemorrhagic injury model was used to induce CPSP in adult male Sprague-Dawley rats. The paw mechanical withdrawal threshold (PMWT) and the paw thermal withdrawal latency (PTWL) were measured in each group before and after modeling. Western blot and Immunofluorescence revealed changes in the expression of mGluR5, TRPV1, and CGRP. In the CPSP group, the PMWT threshold decreased, whereas the PTWL remained unchanged. The expression of mGluR5, TRPV1, and CGRP increased. In the CPSP + Arte group, mGluR5 expression was inhibited by artesunate, which also reversed the reduction of the PMWT threshold in CPSP rats. By intraventricular injection of mGluR5 into the lateral ventricles of CPSP rats, MPEP, a specific inhibitor of mGluR5, inhibits mGluR5 expression and increases the PMWT threshold.