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DOI: 10.1055/a-1217-6777
The Antinociceptive Activities of Certain NSAIDS Combinations in Murine Orofacial Test
Abstract
Pain models are mostly in rodents and between them formalin orofacial test allow discrimination among antinociception and anti-inflammation. This assay use a formalin solution injected into the upper right lip of each mouse which produces two periods of pain separated by an inactive period. The aims of the present study were to evaluate, by means of the isobolographic analysis, the antinociception and anti-inflammatory activities of the following NSAIDs: dexketoprofen, diclofenac, piroxicam and metamizole in an orofacial. The NSAIDs administered intraperitoneally produced a dose-dependent activity with the following order of potency of the rubbing behavior, in phase I: diclofenac>dexketoprofen>piroxicam>metamizole and in the phase II: metamizole>diclofenac>piroxicam>dexketoprofen. The coadministration of NSAIDs resulted in a synergistic interaction, which according to the value of the potency of the combination (II) presents the following range: dexketoprofen plus metamizole>dexketoprofen plus diclofenac>dexketoprofen plus piroxicam, in phase I and dexketoprofen plus metamizole>dexketoprofen plus piroxicam>dexketoprofen plus diclofenac, on the phase II. Data obtained in this work corroborate that NSAIDs alone or in combination inducing activities by additional mechanism of action supplementary to inhibition of COXs. This fact represent a novel approach that could be used as multimodal management of orofacial pain, since with this treatment strategies, by the reduction of doses, can help to diminish side effects of other dugs such opioids.
Publication History
Received: 27 May 2020
Accepted: 06 July 2020
Article published online:
24 July 2020
© Georg Thieme Verlag KG
Stuttgart · New York
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References
- 1 Luccarini P, Childeric A, Gaydier AM. et al. The orofacial formalin Formalin test in the mouse: A behavioral model for studying physiology and modulation Of trigeminal nociception. J Pain 2006; 7: 908-914
- 2 Mogil JS. Animal models of pain: progress and challenges. Nat Rev Neurosci 2009; 10: 283-294
- 3 Patrignani P, Patrono C. Cyclooxygenase inhibitors: From parmacology to clinical read-outs. Biochimica et Biophysica Acta 2015; 1851: 422-432
- 4 Gan TJ. Diclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin 2010; 26: 1715-1731
- 5 Tallarida RJ, Porreca F, Cowan A. Statistical analysis of drug-drug and site-site interactions with isobolograms. Life Sci 1989; 45: 947-961
- 6 Miranda HF, Sierralta F, Pinardi G. An isobolographic analysis of the adrenergic modulation of diclofenac antinociception. Anesth Analg 2001; 93: 430-435
- 7 Muley MM, Krustev E, McDougall JJ. Preclinical assessment of inflammatory pain. CNS Neurosci Therap 2016; 22: 88-101
- 8 Miranda HF, Puig MM, Dursteler C. et al. Dexketoprofen induced antinociception in animal models of acute pain: synergy with morphine and paracetamol. Neuropharmacology 2007; 52: 291-296
- 9 Miranda HF, Sierralta F, Prieto JC. Synergism between NSAIDs in the orofacial formalin test in mice. Pharmacol Biochem Behav 2009; 92: 314-318
- 10 Gonzalez C, Zegpi C, Noriega V. et al. Synergism between dexketoprofen and meloxicam in an orofacial formalin test was not modified by opioid antagonists. Pharmacol Rep 2011; 63: 433-440
- 11 Miranda HF, Noriega V, Sierralta F. et al. Interaction between dexibuprofen and dexketoprofen in the orofacial formalin test in mice. Pharmacol Biochem Behav 2011; 97: 423-427
- 12 Ortiz MI. Metformin and phenformin block the peripheral antinociception induced by diclofenac and indomethacin on the formalin test. Life Siences 2012; 90: 8-12
- 13 Jourdan D, Ardid D, Bardin L. et al. A New automated method of scoring pain in the formalin test in rat. Pain 1997; 71: 265-270
- 14 Jourdan D, Alloui A, Eschalier A. Pharmacological validation of an automated pain scoring method in the formalin test in rats. J Pharmacol Toxicol Methods 1999; 42: 163-170
- 15 Balogh M, Zádori ZS, Lazar B. et al. Central versus peripheral antinociception of a new opioid agonist: acute inflammatory pain in rats. Neurochem Res 2018; 43: 1250-1257
- 16 Barrera NP, Morales B, Torres S. et al. Principles: mechanisms and modeling of synergism in cellular response. Trend Pharmacol Sci 2005; 26: 526-532
- 17 Willoughby DA, Moore AR. Colville-Nash PRCOX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease. Lancet 2000; 355: 646-648
- 18 Zhang W, Jones A, Doherty M. Does Paracetamol (Acetaminophen) Reduce the Pain of Osteoarthritis? A meta-analysis of randomised controlled trials. Ann Rheum Dis 2004; 63: 901-917
- 19 Ahn DK, Chae JM, Choi HS. et al. Central cyclooxygenase inhibitors reduced IL-1beta-induced hyperalgesia in temporomandibular joint of freely moving rats. Pain 2005; 117: 204-213
- 20 Riedel W, Neeck G. Nociception, pain and antinociception: Current concepts. Z Rheumatol 2001; 60: 404-415
- 21 Takemura M, Sugiyo S, Moritani M. et al. Mechanisms of orofacial pain control in the central nervous system. Arch HistoCytol 2006; 69: 79-100
- 22 Dinarello CA. Anti-inflammatory agents. Present and future cell. 2010; 140: 935-950
- 23 Hamza M, Dionne RA. Mechanism of non-opioid analgesics beyond cyclooxygenase enzyme inhibition. Curr Mol Pharmacol 2009; 2: 1-14
- 24 Diaz-Gonzalez F, Sanchez-Madrid F. NSAIDs, learning new trick from old drugs. Eur.J.Immunol 2015; 45: 679-686
- 25 Gunaydin C, Sim Bilge SW. Effects of nonsteroidal anti-inflammatory drugs at the molecular level. Eur J Med 2018; 50: 116-121
- 26 Dwivedi AK, Gurjar V, Kumar A. et al. Molecular basis for nonspecificity of nonsteroidal anti-inflammatory drugs (NSAIDs). Drug Discov 2015; 20: 863-873