Animal models to evaluate analgesic effects using isobolographic analysis

  • María Asunción Romero Molina Universidad Autónoma del Estado de Hidalgo
Keywords: Animal models; Analgesic Effects; Drug combination; Isobolographic Analysis.


In the daily clinical practice, combined pharmacotherapy is often used when a single drug (monotherapy) treatment is not enough to relief moderate-severe pain in patients. The use of experimental animal models offers us great tools for the translation of data from animals to human. However, the accurate design of the preclinical study is a requisite to obtain valid outcomes. Using the isobolographic analysis we can easily establish differences between synergistic or additive responses expected from drug combinations, improving the management and treatment of pain.


Curatolo M, Sveticic G. Drug combinations in pain treatment: to review of the published evidence and to method for finding the optimal combination. Best Pract. Animal Clin. Anaesthesiol. 2002; 16:507–519.
Smith HS. Combination opioid analgesics. Pain Physician 2008; 11:201-214
Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am. J. Surg. 2002; 183:630–641.
Pasero C. Multimodal balanced analgesia in the PACU. J. Perianesth. Nurs. 2003; 18:265–268.
Skinner HB. Multimodal acute pain management. Am. J.Orthop. 2004; 33(Suppl. 5): 5–9.
Hartrick CG. Multimodal postoperative pain management. Am. J. Health-Syst. Pharm. 2004; 61(Suppl. 1): S4–S10.
Joshi GP. Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol. Clin. North America. 2005; 23:185–200.
Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacological Reviews 2001; 53:597:652.
Mogil JS. Animal models of pain: progress and challenges. Nat Rev Neurosci. 2009; 10:283-94.
Jaggi AS, Bhatia N, Kumar N, Singh N, Anand P, Dhawan R. A review on animal models for screening potential anti-stress agents. Neurol Sci. 2011; 32:993-1005.
Jaggi AS, Jain V, Singh N. Animal models of neuropathic pain. Fundam Clin Pharmacol. 2011; 25:1-28.
Tallarida RJ. Drug synergism: its detection and applications. J. Pharmacol. Exp. Ther. 2001; 298:865-72.
Tallarida RJ. An overview of drug combination analysis with isobolograms. J. Pharmacol. Exp. Ther. 2006; 319:1-7.
Tallarida RJ. Revisiting the Isobole and Related Quantitative Methods for Assessing Drug Synergism. J. Pharmacol. Exp. Ther. 2012. DOI:10.1124/jpet.112.193474.
Miranda HF, Puig MM, Romero MA, Prieto JC. Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice. Fundamental & Clinical Pharmacology 2009; 23:81-88.
Romero A, Miranda HF, Puig MM. Analysis of the opioid–opioid combinations according to the nociceptive stimulus in mice. Pharmacological Research 2010; 61:511–518.
Romero A, Miranda HF, Puig MM. Antinociceptive effects of fentanyl, tramadol and their combination, in morphine-tolerant mice. Pharmacol. Biochemical and Behavior 2010; 97:363–369