The analgesic effects of non-steroidal anti-inflammatory drugs on acetylcholine-induced writhing in mice.

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Abstract
The experimental conditions of acetylcholine (ACh)-induced writhing were investigated, and the analgesic effects of non-steroidal anti-inflammatory drugs (NSAID) on ACh-induced writhing were investigated in comparison with those on other writhings. Mice injected (i.p.) with more than 5 mg/kg of ACh showed the writhing response, and the number or writhes were almost equal in all mice. The analgesic effects were evaluated as follows: NSAID were administered orally 30 min before the ACh injection (5 mg/kg i.p.), the number of writhes were counted in each mouse during a period of 10 min following the ACh injection, and mice that did not show any writhing responses were regarded as positive for the analgesic activity. The analgesic effects of NSAID showing the inhibitory effect on prostaglandins (PG) biosynthesis were more potent than those in other writhing tests. The ED50 [median effective dose] values in the ACh-induced writhing were highly correlated with the IC50 [median inhibitory concentration] values in the inhibitory effects on PG biosynthesis (r = 0.81, P < 0.01) and with the ED50 values in the anti-castor oil diarrhea (r = 0.93, P < 0.01). The ED50 values of acidic NSAID in ACh-induced writhing were also highly correlated with the clinical doses (r = 0.90, P < 0.001). The ACh-induced writhing method should be useful for the evaluation of the analgesic effects of acidic NSAID, and the analgesic effects on the ACh-induced writhing are related to their inhibitory effects on PG biosynthesis.