Original Article
  

The Immune Base Therapy of Pain with Magnesium Sulfate on the Trigger Axis of the TNF-α-TRAF6-NF-κB and Its Inhibitor (miR-146a-5p) in Rats

Abstract

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.

1. Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Prim. 2017;3:1–9.
2. Valeberg BT, Rustøen T, Bjordal K, Hanestad BR, Paul S, Miaskowski C. Self-reported prevalence, etiology, and characteristics of pain in oncology outpatients. Eur J Pain. 2008;12(5):582-90.
3. Foley KM. Advances in Cancer Pain. Arch Neurol. 1999;56(4):413-7.
4. XC Z, Zhang JL, Ge CT, Yu YY, Wang P, Yuan TF, et al. Advances in cancer pain from bone metastasis. Drug design, development and therapy. Drug Des Dev Ther. 2015;9:4239–245.
5. Rowinsky EK DR. The clinical pharmacology of paclitaxel (Taxol). InSeminars Oncol. 1993:16-25.
6. De Brabander M, Geuens G, Nuydens R, Willebrords R, De Mey J. Taxol induces the assembly of free microtubules in living cells and blocks the organizing capacity of the centrosomes and kinetochores. Proc Natl Acad Sci. 1981;78(9):5608-12.
7. Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB. Mechanisms of Taxol resistance related to microtubules George. Oncogene. 2003;22(3):7280-95.
8. Postma TJ, Vermorken JB, Liefting AJ, Pinedo HM, Heimans JJ. Paclitaxel-induced neuropathy. Ann Oncol. 1995;6(5):489-94.
9. Cavaletti G, Cavalletti E, Oggioni N, Sottani C, Minoia C, D’Incalci M, et al. Distribution of paclitaxel within the nervous system of the rat after repeated intravenous administration. Neurotoxicology. 2000;21(3):389–94.
10. Markman M, Kennedy A, Webster K, Kulp B, Peterson G, Belinson J. Use of low-dose oral prednisone to prevent paclitaxel-induced arthralgias and myalgias. Gynecol Oncol. 1999;72(1):100–1.
11. Chiu N, Chiu L, Chow R, Lam H, Verma S, Pasetka M, et al. Taxane-induced arthralgia and myalgia: a literature review. J Oncol Pharm Pract. 2017;23(1):56-67.
12. Lipton RB, Apfel SC, Dutcher JP, Rosenberg R, Kaplan J, Berger A, et al. Taxol produces a predominantly sensory neuropathy. Neurology. 1989;39(3):368-73.
13. Leung L, Cahill CM. TNF-α and neuropathic pain-a review. J Neuroinflammation. 2010;7:27.
14. Huehnchen P, Muenzfeld H, Boehmerle W, Endres M. Blockade of IL-6 signaling prevents paclitaxel-induced neuropathy in C57Bl/6 mice. Cell Death Dis. 2020;11(1):1–3.
15. Stepkowski SM, W C, Ross JA, Nagy ZS, Kirken RA. STAT3: an important regulator of multiple cytokine functions. Transplantation. 2008;85(10):1372-7.
16. Tuli HS, Sak K, Iqubal A, Garg VK, Varol M, Sharma U, et al. STAT signaling as a target for intervention: from cancer inflammation and angiogenesis to non-coding RNAs modulation. Mol Biol Rep. 2022;49(9):8987-99.
17. Aisenbrey GA, Corwin E, Catanzarite V. Effect of magnesium sulfate on the vascular actions of norepinephrine and angiotensin II. Am J Perinatol. 1992;9(5-6):477-80.
18. Hyun-Jung S, Na HS DS. Magnesium and Pain. Nutrients. 2020;12(3):2184-97.
19. Su NY, Peng TC, Tsai PS, Huang CJ. Phosphoinositide 3-kinase/Akt pathway is involved in mediating the anti-inflammation effects of magnesium sulfate. J Surg Res. 2013;185(25):726–32.
20. He Y, Sun MM, Zhang GG, Yang J, Chen KS, Xu WW, et al. Targeting PI3K/Akt signal transduction for cancer therapy. Signal transduction and targeted therapy. Signal Transduct Target Ther. 2021;6(8):425–42.
21. Cai Y, Yu X, Hu S, Yu J. A Brief Review on the Mechanisms of miRNA Regulation. Genomics Proteomics Bioinformatics. 2009;7(4):147–54.
22. Tan Y, Yu L, Zhang C, Chen K, Lu J, Tan L. miRNA‑146a attenuates inflammation in an in vitro spinal. Exp Ther Med. 2018;16(4):3703–9.
23. Cuozzo M, Castelli V, Avagliano C, Cimini A, d’Angelo M, Cristiano C RR. Effects of Chronic Oral Probiotic Treatment in Paclitaxel-Induced Neuropathic Pain. Biomedicines. 2021;9(1):346–61.
24. Tsai M, Lu Z, Wang J, Yeh TK, Wientjes MG, JL. A. Effects of Carrier on Disposition and Antitumor Activity of Intraperitoneal Paclitaxel. Pharm Res. 2007;24(3):1691-701.
25. Bagheri G, Rezaee R, Tsarouhas K, Docea AO, Shahraki J, Shahriari M, et al. Magnesium sulfate ameliorates carbon monoxide-induced cerebral injury in male rats. Mol Med Rep. 2019;19(2):1032–9.
26. Shahraki J, Rezaee R, Mohammadzehi Kenar S SNS, Bagheri G, Jahantigh H, et al. Umbelliprenin relieves paclitaxel-induced neuropathy. J Pharm Pharmacol. 2020;72(12):1822–9.
27. Duan YW, SX C, Li QY, Zang Y. Neuroimmune mechanisms underlying neuropathic pain: the potential role of TNF-α-necroptosis pathway. Int J Mol Sci. 2022;23(13):7191–212.
28. Scialli AR, Waterhouse TB, Desesso JM, Rahman A, Goeringer GC. Protective Effect of Liposome Encapsulation on Paclitaxel Developmental Toxicity in the Rat. Teratology. 1997;56(8):305–10.
29. Aryana P, Rajaei S, Bagheri A, Karimi F, Dabbagh A. Acute effect of intravenous administration of magnesium sulfate on serum levels of interleukin-6 and tumor necrosis factor-α in patients undergoing elective coronary bypass graft with cardiopulmonary bypass. Anesthesiol Pain Med. 2014;4.
30. Stickel N, Prinz G, Pfeifer D, Hasselblatt P, Schmitt-Graeff A, Follo M, et al. MiR-146a regulates the TRAF6/TNF-axis in donor T cells during GVHD. Blood, J Am Soc Hematol. 2014;124(8):2586-95.
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Keywords
Immunotherapy Magnesium sulfate MIRN146a microRNA Paclitaxel Pain Rat Tumor necrosis factor-alph
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How to Cite
1.
Bagheri GR, Poursamimi J, Ali-anvari H, Rashki Ghalenoo S, Ghaffari HR. The Immune Base Therapy of Pain with Magnesium Sulfate on the Trigger Axis of the TNF-α-TRAF6-NF-κB and Its Inhibitor (miR-146a-5p) in Rats. Iran J Allergy Asthma Immunol. 2024;:1-9.