Nitridergic Modulation of the Antinociceptive Activity of Rosuvastatin in Mice
Viviana Noriega, Fernando Sierralta, Juan Carlos Prieto, Pilar Zanetta, Hugo F. Miranda
Cardiovascular Department, Clinical Hospital, Universidad de Chile, Santiago, Chile.
Faculty of Medicine, Pharmacy School, Universidad Andres Bello, Santiago, Chile;.
Faculty of Medicine, Pharmacy School, Universidad Andres Bello, Santiago, Chile; Cardiovascular Department, Clinical Hospital, Universidad de Chile, Santiago, Chile;.
Faculty of Odontology, Universidad Finis Terrae, Santiago, Chile; 4Molecular and Clinical Pharmacology Program, Faculty of Medicine, Medical School, Universidad de Chile, Santiago, Chile..
Molecular and Clinical Pharmacology Program, Faculty of Medicine, Medical School, Universidad de Chile, Santiago, Chile..
DOI: 10.4236/pp.2014.51010   PDF   HTML   XML   3,875 Downloads   5,660 Views   Citations


Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been shown that statins have antiinflammatory effects independent of their lipid-lowering effects and these anti-inflammatory effects inhibit the inflammation and pain process. This study evaluated the antinociceptive and anti-inflammatory effects of rosuvastatin using the acetic acid writhing, the formalin hind paw, the orofacial formalin and the hot plate tests. The following experimental group were used: control, acute (1 day) and chronic (3 days) after oral gavage with rosuvastatin (3, 10, 30, 100 and 300 mg/kg). Rosuvastatin produced a dose-dependent antinociception, with different potency, in all the tests. Additionally, nitric oxide synthase inhibitors (Abbreviationsand aminoguanidine) were used to assess the nitric oxide participation on this induced rosuvastatin antinociception. The data demonstrated the antinociceptive and anti-inflammatory activity of rosuvastatin in algesiometer models of tonic or phasic pain. These activities seem to be induced by modulation of iNOS expression, a result that may be relevant in the pharmacological treatment of human pain where rosuvastatin and nitric oxide synthase inhibitors must be used.

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V. Noriega, F. Sierralta, J. Prieto, P. Zanetta and H. Miranda, "Nitridergic Modulation of the Antinociceptive Activity of Rosuvastatin in Mice," Pharmacology & Pharmacy, Vol. 5 No. 1, 2014, pp. 61-68. doi: 10.4236/pp.2014.51010.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] C. Argoff, “Mechanisms of Pain Transmission and Pharmacologic Management,” Current Medical Research Opinion, Vol. 27, No. 10, 2011, pp. 2019-2031.
[2] C. G. García, H. F. Miranda, V. Noriega, F. Sierralta, L. Olavarría, R. Zepeda and J. C. Prieto, “Antinociception Induced by Atorvastatin in Different Pain Models,” Pharmacology Biochemistry and Behavior, Vol. 100, No. 1, 2011, pp. 125-129.
[3] H. F. Miranda, V. Noriega, L. Olavarría, R. J. Zepeda, F. Sierralta and J. C. Prieto, “Antinociception and Anti-Inflamation Induced by Simvastatin in Algesiometric Assays in Mice,” Basic & Clinical Pharmacology & Toxicology, Vol. 109, No. 6, 2011, pp. 438-442.
[4] M. M. Ghaisas, P. R. Dandawatew, S. A. Zawar, Y. S. Ahire and S. P. Gandhi, “Antioxidant, Antinociceptive and Antiinflammatory Activities of Atorvastatin and Rosuvastatin in Various Experimental Models,” Inflammopharmacology, Vol. 18, No. 4, 2010, pp. 169-177.
[5] M. Landsberger, F. Jantzen, S. Konemann and S. B. Felix, “Blockade of Geranylgeranylation by Rosuvastatinupregulatesenos Expression in Human Venous Endothelial cells,” Biochemistry Biophysics Research Communications, Vol. 336, No. 4,2005, pp. 1005-1009.
[6] P. Di Napoli, A. A.Taccardi, A. Grilli, M. A. De Lutiis, A. Barsotti, M. Felaco and R. De Caterina, “Chronic Treatment with Rosuvastatin Modulates Nitric Oxide Synthase Expression and Reduces Ischemia-Reperfusion Injury in Rat Hearts,” Cardiovascular Research, Vol. 66, No. 3, 2005, pp. 462-471.
[7] S. P. Jones, M. F. Gibson, D. M. Rimmer, T. M. Gibson, B. R. Sharp and D. J. Lefer, “Preclinical and Clinical Pharmacology of Rosuvastatin, a New 3-Hydroxy-3-Methylglutaryl Coenzyme a Reductase Inhibitor,” American Journal of Cardiology, Vol. 87, No. 5, 2001, pp. 28B-32B.
[8] P. Luccarini, A. Childereric, A. M. Gayder, D. Voisin and R. Dallel, “The Orofacial Formalin Test in the Mouse, a Behavioural Model for Studying Physiology and Modulation of Trigeminal Nociception,” Journal of Pain, Vol. 7, No. 12, 2006, pp. 908-914.
[9] M. C. Berenbaum, “What Is Synergism?” Pharmacology Review, Vol. 41, No. 2, 1989, pp. 93-141.
[10] H. F. Miranda, M. M. Puig, M. A. Romero and J. C. Prieto, “Effects of Tramadol and Dexketoprofen on Analgesia and Gastrointestinal Transit in Mice,” Fundamental and Clinical Pharmacology, Vol. 23, No. 1, 2009, pp. 81-88.
[11] T. Santodomingo-Garzón, T. M. Cunha, W. A. Verri Jr, D. A. Valério, C. A. Parada and S. Poole, “Atorvastatin Inhibitits Inflammatory Hipernociception,” British Journal of Pharmacology, Vol. 149, No. 1, 2006, pp. 14-22.
[12] G. Weitz-Schmidt, “Statins as Anti-Inflammatory Agents,” Trends Pharmacological Sciences, Vol. 23, No. 10, 2002, pp. 482-487.
[13] U. Schonbeck and P. Libby, “Inflammation, Immunity, and HMG-CoA Reductase Inhibitors: Statins as Antiinflamatory Agents?” Circulation, Vol. 109, No. 1, 2004, pp. 18-26.
[14] N. D. Eddy and D. Leimback, “Synthetic Analgesics. II. Dithyienylbutenyl-Amines and Dithyienylbutylamine,” Journal of Pharmacology and Experimental Therapeutics, Vol. 3, No. 2, 1953, pp. 544-547.
[15] D. L. Simmons, R. M. Botting and H. L. A. Timothy, “Cyclooxygenase Isozymes: The Biology of Prostaglandin Synthesis and Inhibition,” Pharmacology Review, Vol. 56, No. 3, 2004, pp. 387-437.
[16] K. Lee and E. Choi, “Analgesic and Anti-Inflammatory Effects of Liguria Fischeri Leaves in Experimental Animals,” Journal of Ethnopharmacology, Vol. 120, No. 1, 2008, pp. 103-107.
[17] H. Wheeler-Aceto and A. Cowean, “Neurogenic and Tissue Mediated Components of Formalin Induced Edema: Evidence for Supraspinal Regulation,” Agents and Action, Vol. 34, No. 2, 1991, pp. 264-269.
[18] J. Sawynok and A. Ried, “Modulation of Formalin-Induced Behaviors and Edema by Local and Systemic Administration of Dextromethorphan, Memantine and Ketamine,” European Journal of Pharmacology, Vol. 450, No. 1, 2002, pp. 153-162.
[19] M. S. Elkind, “Inflammation, Atherosclerosis, and Stroke,” Neurologist, Vol. 12, No. 1, 2006, pp. 140-148.
[20] M. S. Kostapanos, H. J. Milionis and M. S. Elisaf, “An Overview of the Extra-Lipid Effects of Rosuvastatin,” Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 13, No. 1, 2008, pp. 157-174.
[21] R. Kones, “Rosuvastatin, Inflammation, C-Reactive Protein, JUPITER, and Primary Prevention of Cardiovascular Disease—A Perspective,” Drug Design Development and Therapy, Vol. 4, No. 3, 2010, pp. 383-413.
[22] W. M. Schmidt, A. O. Spiel, B. Jilma, M. Wolzt and M. Müller, “In-Vivo Effects of Simvastatin and Rosuvastatin on Global Gene Expression in Peripheral Blood Leucocytes in a Human Inflammation Model,” Pharmacogenetics Genomics, Vol. 18, No. 1, 2008, pp. 109-120.
[23] X. Q. Shi, T. K. Lim, S. Lee, Y. Q. Zhao and J. Zhang, “Statins Alleviate Experimental Nerve Injury-Induced Neuropathic Pain,” Pain, Vol. 152, No. 5, 2011, pp. 1033-1043.
[24] J. V. Espluges, “NO as a Signalling Molecule in the Nervous System,” British Journal of Pharmacology, Vol. 135, No. 5, 2002, pp. 1079-1095.
[25] Y. Chen, M. K. Boettger, A. Reif, A. Schmitt, N. Uceyler and C. Sommer, “Nitric Oxide Synthase Modulates CFA-Induced Thermal Hyperalgesia through Cytokine Regulation in Mice,” Molecular Pain, Vol. 2, No. 1, 2010, pp. 6-13.
[26] J. Kopincová, A. Púzserová and I. Bernátová, “L-NAME in the Cardiovascular System—Nitric Oxide Synthase Activator?” Pharmacology Reports, Vol. 64, No. 3, 2012, pp. 511-520.

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