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.