Background & Aims

Arthritic pain is a global public health problem. This type of pain is related to conditions such as rheumatoid arthritis, osteoarthritis and gout. The first line of treatment for arthritic pain is the use of non-steroidal anti-inflammatory drugs (NSAIDs). As a second line of treatment, there are opioid-type drugs, whose excellent analgesic properties have been proven. However, the use of these drugs is limited by the adverse effects they produce. Often, a single pharmacological approach is not sufficient to counteract arthritic pain.
AIMS: To determine the antinociceptive effect of the individual and combined administration of celecoxib, and tramadol, on arthritic pain using the “Pain-Induced Functional Impairment in Rats (PIFIR)” experimental model. To identify possible synergistic interactions in the antinociceptive effects of the combination to establish the most optimal doses and to assess the development of pharmacological tolerance after a repeated administration regimen.

Methods

The antinociceptive effect was evaluated using the PIFIR model. Five groups were formed in this study: SHAM control, vehicule control, celecoxib at doses ranging from 1 to 56.2 mg/kg p.o. (CEL), tramadol at doses ranging from 3.2 to 31.6 mg/kg p.o. (TRA), and the combination of CEL (1-31.6 mg/kg, p.o.) + TRA (3.2-23.7 mg/kg, p.o.), resulting in a total of 20 combinations. Determination of the interaction types among these combinations was carried out by the “Synergistic Interaction Surface (SIS)” analysis. For the evaluation of pharmacological tolerance, a repeated administration scheme was applied, consisting of three daily administrations for four consecutive days.

Results

CEL and TRA individually exhibited a dose-dependent antinociceptive effect. When co-administered, interactions were mostly detected as supra-additive and additive. The combination that generated the highest level of efficacy was celecoxib at 17.8 mg/kg with tramadol at 23.7 mg/kg. The combination with the highest degree of potentiation was celecoxib at 3.2 mg/kg with tramadol at 10 mg/kg. Subsequently, the most effective doses of each individual drug, CEL at 56.2 mg/kg and TRA at 31.6 mg/kg, were evaluated, as well as the combination with the highest degree of efficacy; CEL at 17.8 mg/kg combined with TRA at 23.7 mg/kg, after a scheme of 12 repeated subcutaneous administrations. The dose of CEL at 56.2 mg/kg was found to reduce its effect by 52%, the dose of TRA at 31.6 mg/kg also reduced its effect by 99.27%, and the combination also reduced its effect by 85.29% after the repeated administration regimen.

Conclusions

CEL and TRA individually exhibit antinociceptive effects, and their co-administration generates mostly supra-additive and additive effects in different proportions under these experimental conditions. When a repeated administration regimen is employed, the antinociceptive effects of their most effective individual doses decrease as well as in the case of the combination.

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Presenting Author

Valeria Aranda-Bahena

Poster Authors

Valeria Aranda Bahena

Master's student

Center for Research and Advanced Studies of the National Polytechnic Institute

Lead Author

E-mail

Topics

  • Models: Chronic Pain - Inflammatory