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Gender differences in the antinociceptive effect of tramadol, alone or in combination with gabapentin, in mice

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Journal of Biomedical Science

Abstract

Gender difference in the antinociceptive effect of tramadol and gabapentin (alone or in combination) were investigated in mice. For investigation of acute antinociceptive effect, tramadol and gabapentin were administered to mice by intraperitoneal injection and per os, respectively, and antinociceptive activity was measured by the tail-flick test 30 min after drug administration. For investigation of the development of antinociceptive tolerance to analgesics, mice were injected with tramadol (60 mg/kg), alone or in combination with gabapentin (75 mg/kg), twice daily for seven consecutive days and the tail-flicks were tested on experimental days 1, 3, 5 and 7. Results showed there was a lower ED50 value of tramadol antinociception in males than in females, indicating that females were less sensitive to the drug. Gabapentin produces a limited antinociception in both males and females. The combination of gabapentin and tramadol produced synergistic effect without gender difference. Repeated administration of tramadol produced antinociceptive tolerance in both genders. Gabapentin produced synergistic effect in tramadol-tolerant mice and repeated administration of gabapentin did not alter the synergistic effect in tramadol-tolerant mice. Because females show a higher overall prevalence of pain and less sensitivity to opioids, our finding may suggest a clinical significance of combined use of the two drugs.

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Acknowledgements

The authors gratefully thank Dr. Whitney Wiltshire, Dr. Ike Eriator, and Mrs. Marsha Manuel for their careful proofreading of the manuscript.

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Authors and Affiliations

  1. Department of Anesthesiology, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Xiaoli Dai & Claude D. Brunson

  2. Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Robin W. Rockhold, Ing K. Ho & Tangeng Ma

  3. Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, 55455, USA

    Horace H. Loh

  4. Division of Mental Health and Substance Abuse Research, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan

    Ing K. Ho

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  1. Xiaoli Dai
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  2. Claude D. Brunson
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Correspondence to Tangeng Ma.

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Dai, X., Brunson, C.D., Rockhold, R.W. et al. Gender differences in the antinociceptive effect of tramadol, alone or in combination with gabapentin, in mice. J Biomed Sci 15, 645–651 (2008). https://doi.org/10.1007/s11373-008-9252-0

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  • DOI: https://doi.org/10.1007/s11373-008-9252-0

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