MCTR1 alleviates remifentanil-induced hyperalgesia by regulating mitochondrial fission protein DRP1 in rats

Objective This study aimed to investigate whether Maresin conjugates in tissue regeneration-1 (MCTR1) can alleviate remifentanil-induced hyperalgesia (RIH) by modulating the mitochondrial fission protein dynamin-related protein 1 (DRP1). Methods Pain behavioral tests were conducted 24 h before remifentanil infusion and at 4, 8, and 24 h postinfusion. The expression of DRP1 and NR 2 B was assessed by Western Blot (WB). Additionally, intrathecal injections of MCTR1 were administered to evaluate the effects on RIH development and progression. Behavioral tests were conducted, meanwhile, the levels of DRP1, NR 2 B in the spinal cord, superoxide, including malondialdehyde (MDA), glutathione, and reactive oxygen species (ROS) in the spinal dorsal horn were measured. Mitochondrial numbers were counted via transmission electron-microscopy. Results After remifentanil administration, rats exhibited mechanical allodynia and thermal hyperalgesia, along with an increase in spinal levels of DRP1 and NR 2 B. However, MCTR1-treated rats showed alleviation of remifentanil-induced mechanical and thermal hyperalgesia, accompanied by reduced NR 2 B expression. Notably, MCTR1 treatment also led to decreased DRP1 expression and mitochondrial fission, as well as reduced MDA content and ROS production. Conclusion MCTR1 exerts a preventive effect on RIH by modulating NR 2 B activity through the DRP1-mitochondrial-ROS pathway.