Quercetin Reduces Antinociceptive but Not the Anti-Inflammatory Effects of Indomethacin, Ketorolac, and Celecoxib in Rats with Gout-Like Pain

The objective of this study was to determine the pharmacological interaction of some common NSAIDs in the presence of quercetin (QUER). Indomethacin (IND), ketorolac (KET), or celecoxib (CEL) were assessed alone and in combination with QUER using experimental gout-arthritic pain and the carrageenan-induced edema test in rats to evaluate their antinociceptive and anti-inflammatory effects, respectively. The antinociceptive effect of each NSAID was also analyzed after the repeated administration of QUER for 10 days. Molecular docking analysis on COX-1/COX-2 with each drug was explored to analyze the pharmacological interaction. QUER produced minimal antinociceptive or anti-inflammatory effects on experimental gout-arthritic pain or on the carrageenan-induced edema in rats. Additionally, QUER reduced the antinociceptive effect of NSAIDs, mainly those COX-1 inhibitors (IND and KET), when they were combined. However, QUER did not modify the anti-inflammatory effect of these COX-1 inhibitors and slightly improved the anti-inflammatory effect of the COX-2 inhibitor (CEL). According to the docking analysis, COX-1 and COX-2 are likely implicated in these pharmacological interactions. In conclusion, QUER, a known bioactive natural product, may alter the antinociceptive efficacy of NSAIDs commonly used to relieve gout-like pain and suggests not using them together to prevent a negative therapeutic interaction in this effect.