Influence of formalin concentration on the antinociceptive effects of anti-inflammatory drugs in the formalin test in rats: separate mechanisms underlying the nociceptive effects of low- and high-concentration formalin

The present study has assessed the relationship between formalin-induced nociception and formalin-induced inflammation by comparing the dose-related effects of anti-inflammatory treatments on both nociceptive scores and plasma extravasation in the rat hind paw in response to high and low concentrations of formalin. The degree of plasma extravasation produced by 1% formalin did not differ significantly from that produced by the same volume of saline, and was not significantly affected by either of the anti-inflammatory agents. The 5% formalin injection produced significant plasma extravasation that was dose-dependently reduced by both dexamethasone and ibuprofen. The early-phase nociceptive responses to either 1 or 5% formalin were not affected significantly by either of the anti-inflammatory agents. In contrast, the late-phase nociceptive responses to 5%, but not 1%, formalin were dose-dependently reduced by both dexamethasone and ibuprofen. The present study suggests that there is a positive correlation between the nociceptive and inflammatory effects of formalin in the rat hind paw. However, only a high concentration of formalin, which produces significant plasma extravasation, is capable of demonstrating the antinociceptive effects of anti-inflammatory agents, and the effects are restricted to the late phase of the formalin test.