Evaluation of the tail formalin test in mice as a new model to assess local analgesic effects

Opioids are effective topical analgesics in the radiant heat tailflick assay and display synergistic interactions with a number of other classes of drugs. To determine whether these actions extend to other types of nociception, we examined the actions of topical morphine and lidocaine in a tail formalin assay in the mouse. Formalin responses in the tail were similar to those seen in the hind paw, but were limited to licking. Unlike the traditional hind paw assay, the time-course of nociceptive behavior in the tail was monophasic; lasting 40-60 min. Morphine, MK-801 and acetylsalicylic acid (ASA) were active systemically in the tail formalin assay with potencies similar to those seen in the second phase of the paw formalin test. Both morphine and lidocaine were active topically in the tail formalin assay, although their time-course of action appeared to be shorter than that of the formalin. However, morphine displayed ceiling effect not seen when it was administered systemically. Lidocaine also had a ceiling effect. When given together, the response to the combination was supra-additive, consistent with our prior studies showing synergy in the radiant heat tailflick assay. These studies validate the formalin assay in the tail and support the topical actions of opioids and other drugs in a second pain model. They also suggest supra-additive interactions between morphine and lidocaine similar to those previously seen. The tail formalin assay will be valuable in assessing the activity of topical drugs.