Acetaminophen effects upon formalin-evoked flinching, postformalin, and postincisional allodynia and conditioned place preference.

INTRODUCTION

We explored in mice, the analgesic, tolerance, dependency, and rewarding effects of systemic acetaminophen (APAP).

METHODS

Studies employed adult mice (C57Bl6). (1) . Mice were given intraperitoneal APAP in a DMSO (5%)/Tween 80 (5%) or a water-based formulation before formalin flinching on day 1 and tactile thresholds assessed before and after APAP at day 12. (2) At 24 hours and 8 days after hind paw incision in male mice, effects of intraperitoneal APAP on tactile allodynia were assessed. (3) . Mice received daily (4 days) analgesic doses of APAP or vehicle and tested upon formalin flinching on day 5. (4) . For 3 consecutive days, vehicle was given in the morning in either of 2 chambers and in each afternoon, an analgesic dose of morphine or APAP in the other chamber. On days 5 and 10, animals were allowed to select a "preferred" chamber.

RESULTS

Formalin in male mice resulted in biphasic flinching and an enduring postformalin tactile allodynia. Acetaminophen dose dependently decreased phase 2 flinching, and reversed allodynia was observed postflinching. At a comparable APAP dose, female mice showed similarly reduced phase 2 flinching. Incision allodynia was transiently reversed by APAP. Repeated APAP delivery showed no loss of effect after sequential injections or signs of withdrawal. Morphine, but not APAP or vehicle, resulted in robust place preference.

CONCLUSIONS

APAP decreased flinching and allodynia observed following formalin and paw incision and an absence of tolerance, dependence, or rewarding properties.