Pregabalin antinociception and its interaction with tramadol in acute model of pain.
BACKGROUND
The aim of present study was to investigate the antinociceptive effect of pregabalin and tramadol either alone and or in combination on acute model of pain.


METHODS
The antinociceptive effect of intraperitoneal administration of pregabalin (1 to 400 mg/kg) and tramadol (10 to 80 mg/kg) or combination of them were measured after 30 and 60 min on hot-plate in terms of maximum possible effect (%MPE) in mice.


RESULTS
Antinociceptive effect rose significantly for both pregabalin at doses 200 and 400 mg/kg and tramadol from 20 to 80 mg/kg in dose dependent manner. From linear equation the doses that increased antinociceptive effect by 50% (ED(50)) were 69 ± 8.2 mg/kg for tramadol and 246 ± 24 mg/kg for pregabalin. Unlike pregabalin, %MPE(30) (at 30(th) min) of tramadol was significantly higher than its %MPE(60). The interaction after co-administration of non analgesic dose of 10 mg/kg of pregabalin with low analgesic dose of 30 mg/kg of tramadol resulted super-additive and %MPE(30) and %MPE(60) were increased compared to each drug alone. In all other combination groups, the interaction were sub-additive particularly when non analgesic doses of each drug (10 mg/kg) were co-administrated and %MPE was decreased significantly compared to that of each drug alone.


CONCLUSIONS
Pregabalin revealed a comparative antinociceptive effect as similar to tramadol in acute model of pain, but interaction between these two drugs depends highly on their proportion in the combination. The analgesia may increase but adverse effects such as seizurogenic effect of tramadol can be reduced in clinical setting if right proportion is used. More studies are required to understand the mechanisms and clinical implication of such combinations.
Department of Pharmacology, Tehran University of Medical Sciences, Hemmat Pardis, Hemmat highway, 1449614535 Tehran, Iran.
Manzumeh Shamsi
MS
Meymandi
Fariborz
F
Keyhanfar
D059787:Acute Pain / Q000188:drug therapy*; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D010146:Pain; D000069583:Pregabalin; D013997:Time Factors; D014147:Tramadol / Q000008:administration & dosage / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000700:Analgesics; D000701:Analgesics, Opioid; D014147:Tramadol; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid