Abstract
Recent studies have shown that sugammadex’s effects on the nervous system are controversial and its effect on nociception, morphine analgesia and tolerance is still unclear. The current study aimed to examine the possible involvement of sugammadex on nociception, morphine analgesia, and morphine tolerance development involving oxidative stress and NOD-like receptor protein 3 (NLRP3)/Interleukin-1β (IL-1β) signaling pathways in rats. The animals, thirty-six male Wistar Albino rats, were separated into six groups (n = 6 for each group): saline, sugammadex, morphine, morphine + sugammadex, morphine tolerance, and morphine tolerance + sugammadex. The analgesic effects were measured by analgesia tests (the tail-flick and hot plate). Oxidative stress parameters, NLRP3/IL-1β signaling pathway, and apoptotic proteins in the dorsal root ganglion (DRG) tissues were measured using Enzyme-Linked ImmunoSorbent Assay (ELISA) kits. Sugammadex had no antinociceptive activity when administered alone. However, it improved morphine’s analgesic efficacy and inhibited the development of morphine tolerance. In addition, it decreased oxidative stress and NLRP3/IL-1β signaling pathway proteins in the DRG when administered with single and repeated doses of morphine. Besides, sugammadex lowered apoptotic proteins in the DRG following tolerance development. Thus, we may conclude that the ability of sugammadex to affect morphine pharmacological activity may be mediated by the suppression of oxidative stress and the NLRP3/IL-1β pathway.
REFERENCES
Ozdemir, E., Demirkazik, A., Gursoy, S., Taskıran, A.S., Kilinc, O., and Arslan, G., Gen. Physiol. Biophys., 2017, vol. 36, pp. 415–422.
Zhang, X., Bao, L., and Li, S., Br. J. Pharmacol., 2015, vol. 172, pp. 364–374.
Chen, Y., Geis, C., and Sommer, C., J. Neurosci., 2008, vol. 28, pp. 5836–5845.
Wang, X., Loram, L.C., Ramos, K., de Jesus, A.J., Thomas, J., Cheng, K., Reddy, A., Somogyi, A.A., Hutchinson, M.R., Watkins, L.R., and Yin, H., Proc. Natl Acad. Sci. USA, 2012, vol. 109, pp. 6325–6330.
Mao, J., Sung, B., Ji, R.R., and Lim, G., J. Neurosci., 2002, vol. 22, pp. 7650–7661.
Schroder, K. and Tschopp, J., Cell, 2010, vol. 140, pp. 821–832.
Schroder, K., Zhou, R., and Tschopp, J., Science, 2010, vol. 327, pp. 296–300.
Lamkanfi, M. and Dixit, V.M., Annu. Rev. Cell. Dev. Biol., 2012, vol. 28, pp. 137–161.
Grace, P.M., Strand, K.A., Galer, E.L., Urban, D.J., Wang, X., Baratta, M.V., Fabisiak, T.J., Anderson, N.D., Cheng, K., Greene, L.I., Berkelhammer. D., Zhang, Y., Ellis, A.L., Yin, H.H., Campeau, S., Rice, K.C., Roth, B.L., Maier, S.F., and Watkins, L.R., Proc. Natl. Acad. Sci. U S A, 2016, vol. 113, pp. E3441–E3450.
Cai, Y., Kong, H., Pan, Y.B., Jiang, L., Pan, X.X., Hu, L., Qian, Y.N., Jiang, C.Y., Liu, W.T., J Neuroinflammation, 2016, vol. 13, pp. 53.
Naguib, M., Anesth. Analg., 2007, vol. 104, pp. 575–581.
Ozbilgin, S., Yılmaz, O., Ergur, B.U., Hancı, V., Ozbal, S., Yurtlu, S., Gunenc, S.F., Kuvaki, B., Kucuk, B.A., and Sisman, A.R., Kaohsiung. J. Med. Sci., 2016, vol. 32, pp. 292–301.
Abrishami, A., Ho, J., Wong, J., Yin, L., and Chung, F., Cochrane Database Syst. Rev., 2009.
Palanca, J.M., Aguirre-Rueda, D., Granell, M.V., Aldasoro, M., Garcia, A., Iradi, A., Obrador, E., Mauricio, M.D., Vila, J., Gil-Bisquert, A., and Valles, S.L., Int. J. Med. Sci., 2013, vol. 10, pp. 1278–1285.
Uludağ, Ö., Kafkas Univ. Vet. Fak. Derg., 2019, vol. 25, pp. 793–799.
Alagöz, A., Küçükgüçlü, S., Boztaş, N., Hancı, V., Yuluğ, E., and Şişman, A.R., Ulus Travma ve Acil Cerrahi Derg., 2020, vol. 26, pp. 509–516.
Hoshijima, H., Doi, K., Nagasaka, H., Takeuchi R., Saudi J. Anaesth., 2014, vol. 8, p. 418.
Kelsaka, E., Karakaya, D., and Zengin, E.C., Med. Princ. Pract., 2013, vol. 22, pp. 304–306.
Dirik, H., Joha, Z., Fundam. Clin. Pharmacol., 2023, vol. 37, pp. 786–793.
Koç, A., Kuyrukluyildiz, U., Gazi, M., Caner Sayar, A., Altuner, D., Süleyman, H., Yavuzer, B., Abdulkadir Çoban, T., Süleyman, Z., Naz Yazici, G., Gen. Physiol. Biophys., 2023, vol. 42, pp. 67–75.
Kip, G., Turgut, H.C., Alkan, M., Aydin, M.E., Erbatur, M.E., Kiraz, H.A., Kartal, S., Boyunaga, H., Comu, F.M., Erdem, O., Arslan, M., and Unal, Y., Bratislava Med. J., 2015, vol. 116, pp. 746–750.
Avci, O. and Taskiran, A.Ş., TURKISH J. Med. Sci., 2020, vol. 50, pp. 2048–2058.
Taskiran, A.S. and Avci, O., Neurosci. Lett., 2021, vol. 741, p. 135504.
Kruger, N.J., Handbook, New Jersey: Humana Press, 1994, pp. 15–22.
Abdel-Zaher, A.O., Mostafa, M.G., Farghly, H.M., Hamdy, M.M., Omran, G.A., and Al-Shaibani, N.K.M., Eur. J. Pharmacol., 2013, vol. 702, pp. 62–70.
Muscoli, C., Cuzzocrea, S., Ndengele, M.M., Mollace, V., Porreca, F., Fabrizi, F., Esposito, E., Masini, E., and Matuschak, G.M., J. Clin. Invest., 2007, vol. 117, pp. 3530–3539.
Yang, F., Wang, Z., Wei, X., Han, H., Meng, X., Zhang, Y., Shi, W., Li, F., **n, T., Pang, Q., and Yi, F., J Cereb. Blood. Flow Metab., 2014, vol. 34, pp. 660–667.
Geldhoff, M., Mook-Kanamori, B.B., Brouwer, M.C., Valls Seron, M., Baas, F., van der Ende, A., and van de Beek, D., Immunogenetics, 2013, vol. 65, pp. 9–16.
Bossù, P., Ciaramella, A., Salani, F., Vanni, D., Palladino, I., Caltagirone, C., and Scapigliati, G., Curr. Pharm. Des., 2011, vol. 16, pp. 4213–4224.
Wilms, H., Sievers, J., Rickert, U., Rostami-Yazdi, M., Mrowietz, U., and Lucius, R., J. Neuroinflammation, 2010, vol. 7, pp. 30.
DeLeo, J.A., Tanga, F.Y., and Tawfik, V.L., Neuroscientist, 2004, vol. 10, pp. 40–52.
Qu, J., Tao, X.Y., Teng, P., Zhang, Y., Guo, C.L., Hu, L., Qian, Y.N., Jiang, C.Y., and Liu, W.T., J. Neuroinflammation, 2017, vol. 14, p. 228.
Liu, Q., Su, L.Y., Sun, C., Jiao, L., Miao, Y., Xu, M., Luo, R., Zuo, X., Zhou, R., Zheng, P., **ong, W., Xue, T., Yao, Y.G., Redox Biol., 2020, vol. 34, pp. 101560.
Ueda, H., Ueda, M., Front Biosci., 2009, vol. 14, pp. 5260–5272.
Mika, J., Wawrzczak-Bargiela, A., Osikowicz, M., Makuch, W., Przewlocka, B., Brain Behav Immun, 2009, vol. 23, pp. 75–84.
**e, X.J., Ma, L.G., **, K., Fan, D.M., Li, J.G., Zhang, Q., Zhang, W., Mol Pain, 2017, vol. 13, pp. 1744806917706582.
Zhang, Y., Wang, K., Lin, M., Li, Q., Hong, Y., Eur J Pharmacol, 2017, vol. 815, pp. 10–17.
Hu, S., Sheng, W.S., Lokensgard, J.R., Peterson, P.K., Neuropharmacology, 2002, vol. 42, pp. 829–836.
Mao, J., Sung, B., Ji, R.R., Lim, G., J Neurosci, 2002, vol. 22, pp. 7650–7661.
Satomoto, M., Sun, Z., Adachi, Y.U., Makita, K., Anesthesiol Res Pract, 2016, pp. 1–6.
Mucuoglu, A.O., Mucuoglu, C.A., Kizmazoglu, C., Ersoy, N., Micili, S.C., Karabay, N., Hanci, V., Kalemci, O., J Craniofac Surg, 2022, vol. 33, pp. 1260–1264.
ACKNOWLEDGMENTS
The authors would like to thank the Sivas Cumhuriyet University, School of Medicine, CUTFAM Research Center, Sivas, Turkey, for providing the necessary facilities to conduct this study.
Funding
This work was supported by ongoing institutional funding. No additional grants to carry out or direct this particular research were obtained.
Author information
Authors and Affiliations
Contributions
Ahmet Sevki Taskiran: Investigation, conceptualization, writing-review, and editing. Onur Avci: Methodology, data curation, formal analysis, writing the original draft.
Corresponding author
Ethics declarations
ETHICS APPROVAL AND CONSENT TO PARTICIPATE
Experimental protocols were approved by Sivas Cumhuriyet University Animal Ethics Committee (Approval number: 65202830-050.04.04-436).
CONFLICT OF INTEREST
The authors of this work declare that they have no conflicts of interest.
Additional information
Publisher’s Note.
Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ahmet Sevki Taskiran, Onur Avci Sugammadex Potentiation of Morphine Analgesia and Reduction of Opioid Tolerance Is Accompanied by Inhibition of Oxidative Stress and the NLRP3/IL-1β Signaling Pathway in the Rat Dorsal Root Ganglion. Neurochem. J. 18, 162–170 (2024). https://doi.org/10.1134/S1819712424010227
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1819712424010227