Gender differences in the antinociceptive effect of tramadol,alone or in combination with gabapentin,in mice |
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Authors: | Xiaoli Dai Claude D Brunson Robin W Rockhold Horace H Loh Ing K Ho Tangeng Ma |
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Institution: | (1) Department of Anesthesiology, University of Mississippi Medical Center, Jackson, MS 39216, USA;(2) Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA;(3) Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA;(4) Division of Mental Health and Substance Abuse Research, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan |
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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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Keywords: | Tramadol Gabapentin Pain Antinociception Tolerance Mice Tail-flick Opioid receptor Gender |
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