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Enhancement of antinociception by co-administration of ibuprofen and caffeine in arthritic rats.
Eur J Pharmacol. 2006 Aug 21; 544(1-3):31-8.EJ

Abstract

It has been observed that caffeine improves antinociceptive efficacy of some non-steroidal antiinflammatory drugs (NSAIDs) in several experimental models, however, these effects have been questioned in humans. Controversy in clinical studies may be due to the use of different protocols as well as to high interindividual variability in patient response. In addition, the antinociceptive interaction of ibuprofen+caffeine has not been studied. To assess a possible synergistic antinociceptive interaction, the antinociceptive effects of ibuprofen, and caffeine administered either separately or in combinations were determined in a model of arthritic pain: "Pain-induced functional impairment in the rat (PIFIR model). The antinociceptive efficacies were evaluated using several dose-response curves and time courses. The antinociceptive effects from the combination that produced the greater effect were compared with the maximal antinociceptive effect of either morphine or acetylsalicylic acid alone. The animals were administered with 0.05 ml intra-articular (i.a.) of uric acid to induce nociception. Groups of six rats received either acetylsalicylic acid, morphine, ibuprofen or caffeine, or a combination ibuprofen+caffeine (18 combinations). We report here that caffeine (17.8 and 31.6 mg/kg) is able to potentiate the antinociceptive effect of ibuprofen. This investigation showed that six combinations presented effects of potentiation and twelve combinations only showed antinociceptive effects not different from that of ibuprofen alone. The maximum antinociceptive effect was 270.7+/-12.7 area units (au), produced by ibuprofen 100 mg/kg+caffeine 17.8 mg/kg; this effect was greater than the maximum produced by morphine 17.8 mg/kg (244.7+/-22.9 au) in these experimental conditions. The maximum potentiation was 197 % produced with the combination of ibuprofen 17.8 mg/kg+caffeine 17.8 mg/kg. These results suggest that the antinociceptive effect of ibuprofen was significantly potentiated by doses of caffeine that by themselves are ineffective in this model.

Authors+Show Affiliations

Departamento de Sistemas Biológicos, UAM-Xochimilco, México D.F., México.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16872598

Citation

López, José Raúl Medina, et al. "Enhancement of Antinociception By Co-administration of Ibuprofen and Caffeine in Arthritic Rats." European Journal of Pharmacology, vol. 544, no. 1-3, 2006, pp. 31-8.
López JR, Domínguez-Ramírez AM, Cook HJ, et al. Enhancement of antinociception by co-administration of ibuprofen and caffeine in arthritic rats. Eur J Pharmacol. 2006;544(1-3):31-8.
López, J. R., Domínguez-Ramírez, A. M., Cook, H. J., Bravo, G., Díaz-Reval, M. I., Déciga-Campos, M., & López-Muñoz, F. J. (2006). Enhancement of antinociception by co-administration of ibuprofen and caffeine in arthritic rats. European Journal of Pharmacology, 544(1-3), 31-8.
López JR, et al. Enhancement of Antinociception By Co-administration of Ibuprofen and Caffeine in Arthritic Rats. Eur J Pharmacol. 2006 Aug 21;544(1-3):31-8. PubMed PMID: 16872598.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of antinociception by co-administration of ibuprofen and caffeine in arthritic rats. AU - López,José Raúl Medina, AU - Domínguez-Ramírez,Adriana Miriam, AU - Cook,Helgi Jung, AU - Bravo,Guadalupe, AU - Díaz-Reval,Ma Irene, AU - Déciga-Campos,Myrna, AU - López-Muñoz,Francisco Javier, Y1 - 2006/06/27/ PY - 2006/02/03/received PY - 2006/06/13/revised PY - 2006/06/19/accepted PY - 2006/7/29/pubmed PY - 2007/1/16/medline PY - 2006/7/29/entrez SP - 31 EP - 8 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 544 IS - 1-3 N2 - It has been observed that caffeine improves antinociceptive efficacy of some non-steroidal antiinflammatory drugs (NSAIDs) in several experimental models, however, these effects have been questioned in humans. Controversy in clinical studies may be due to the use of different protocols as well as to high interindividual variability in patient response. In addition, the antinociceptive interaction of ibuprofen+caffeine has not been studied. To assess a possible synergistic antinociceptive interaction, the antinociceptive effects of ibuprofen, and caffeine administered either separately or in combinations were determined in a model of arthritic pain: "Pain-induced functional impairment in the rat (PIFIR model). The antinociceptive efficacies were evaluated using several dose-response curves and time courses. The antinociceptive effects from the combination that produced the greater effect were compared with the maximal antinociceptive effect of either morphine or acetylsalicylic acid alone. The animals were administered with 0.05 ml intra-articular (i.a.) of uric acid to induce nociception. Groups of six rats received either acetylsalicylic acid, morphine, ibuprofen or caffeine, or a combination ibuprofen+caffeine (18 combinations). We report here that caffeine (17.8 and 31.6 mg/kg) is able to potentiate the antinociceptive effect of ibuprofen. This investigation showed that six combinations presented effects of potentiation and twelve combinations only showed antinociceptive effects not different from that of ibuprofen alone. The maximum antinociceptive effect was 270.7+/-12.7 area units (au), produced by ibuprofen 100 mg/kg+caffeine 17.8 mg/kg; this effect was greater than the maximum produced by morphine 17.8 mg/kg (244.7+/-22.9 au) in these experimental conditions. The maximum potentiation was 197 % produced with the combination of ibuprofen 17.8 mg/kg+caffeine 17.8 mg/kg. These results suggest that the antinociceptive effect of ibuprofen was significantly potentiated by doses of caffeine that by themselves are ineffective in this model. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/16872598/Enhancement_of_antinociception_by_co_administration_of_ibuprofen_and_caffeine_in_arthritic_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00664-9 DB - PRIME DP - Unbound Medicine ER -