Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 2 2025 03 10 180 186 EN Gholam Reza Bagheri Department of Nutrition, School of Health, Zabol University of Medical Sciences, Zabol, Iran Javad Poursamimi Department of Immunology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran. Hadi Ali-anvari Department of Anesthesiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran Sara Rashki Ghalenoo Department of Cardiology, Zabol University of Medical Sciences, Zabol, Iran Hamid Reza Ghaffari Department of Basic Sciences, School of Medicine, Zabol University of Medical Sciences, Zabol 2024 06 27 2024 08 24 europathic pain can arise from injury or illness affecting the somatosensory system. It can also be triggered by cancer or chemotherapy drugs like paclitaxel. Researchers have indicated that magnesium sulfate may help in preventing neuropathy. This study aimed to investigate the effect of magnesium sulfate on paclitaxel-induced neuropathic pain by inhibiting the Tumor Necrosis Factor (TNF) Alpha - receptor-associated factor 6 - Nuclear factor kappa-light-chain-enhancer of activated B cells (TNF-α-TRAF6-NF-κB) axis. Twenty-four male rats were divided into four groups: experiment group (E)-1, E2, E3, and the control group (Co). The experimental groups and the control group received paclitaxel at a dosage of 8 mg/kg every other day, totaling four injections over seven days. In addition, magnesium sulfate was administered daily in three doses of 300, 150, and 75 mg/kg, amounting to seven injections over the course of seven days. On the seventh day, peripheral blood samples were collected from the rats, and sera were used for the analysis of TNF-α serum levels and MicroRNA-146a-5p expression using ELISA and qRT-PCR methods, respectively. The serum levels of TNF-α increased in the E1, E2, and E3 groups compared to the control group. However, there was a gradual decrease in the E1, E2 and E3 groups. The miR-146a-5p expression declined in the E1 group and increased in the E2 and E3 groups compared to the control group. This study demonstrated that administering 300 and 150 mg of magnesium sulfate decreased TNF-α synthesis and reduced the function of the TNF-α-TRAF6-NF-κB axis during the initiation step. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4133 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4133/2135 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4133/2185