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Evaluation of dosages and routes of administration of tramadol analgesia in rats using hot-plate and tail-flick tests

Lab Animal volume 39, pages 342–351 (2010)Cite this article

Abstract

Tramadol is an opioid-like analgesic with relatively mild side effects. Because it is inexpensive and is not classified as a controlled substance by the US federal government, the authors wanted to evaluate its applicability as a practical and effective analgesic in male Sprague Dawley rats. They measured the efficacy of four dosages (4, 12.5, 25 or 50 mg tramadol per kg body weight) and three routes of administration (per os (p.o.) in a flavored gelatin cube, subcutaneous (s.c.) or intraperitoneal (i.p.)) using the hot-plate test and the tail-flick test, which were carried out 1 week apart. Rats that were dosed p.o. were given flavored gelatin cubes without tramadol on the 2 d before testing to help them become acclimated to the gelatin, in an effort to increase the likelihood that they would consume the gelatin on the testing day. Results from the hot-plate and tail-flick tests for rats that were given tramadol p.o. were similar before and after administration, regardless of tramadol dosage, suggesting that this route of administration was not effective. The s.c. route of administration was effective at dosages of 25 mg and 50 mg tramadol per kg body weight, although these dosages also resulted in sedation and skin lesions. The i.p. route of administration was also effective at dosages of 12.5 mg, 25 mg and 50 mg tramadol per kg body weight, though sedation was observed at dosages of 25 mg and 50 mg per kg body weight. Intraperitoneal administration of 12.5 mg tramadol per kg body weight had no notable side effects, and the authors plan to further study this dosage and route of administration in a rodent surgical model of pain.

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Figure 1
Figure 2: Latency in rats' responses to acute thermal pain.
Figure 3: Epidermal changes consisted of coagulative necrosis of the epidermis and dermis (arrowheads), overlying focal cavitating necrosis and edema, hemorrhage and fibrin (asterisk), bordered by zones of inflammation and granulation tissue.
Figure 4: Cutaneous lesions extended from the epidermis to the deep muscular layers and were characterized by a central area of cavitating necrosis (asterisk) admixed with fibrin, neutrophils and edema, bordered by zones of granulation tissue (arrowheads), skeletal muscle degeneration, necrosis and mineralization with granulomatous inflammation (arrows).

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Acknowledgements

We thank Danielle Waxer, Page Myers, James Clark, Sandy Hackney, Jenetta Jackson and Keisha Chavis for their assistance and support of the research and care of the animals. We thank Dr. Larry Wright for assistance in literature evaluation. We thank Dr. Sheryl Moy, Dr. Greg Travlos and Dr. Gregory Cannon for their extensive reviews of the manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences.

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Authors and Affiliations

  1. Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC

    Coralie Zegre Cannon,  Mark J. Hoenerhoff &  Angela P. King-Herbert

  2. Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC

    Grace E. Kissling

  3. Comparative Medicine Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC

    Terry Blankenship-Paris

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Correspondence to Coralie Zegre Cannon.

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Cannon, C., Kissling, G., Hoenerhoff, M. et al. Evaluation of dosages and routes of administration of tramadol analgesia in rats using hot-plate and tail-flick tests. Lab Anim 39, 342–351 (2010). https://doi.org/10.1038/laban1110-342

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