The combination of
indomethacin,
caffeine, and
prochlorperazine (hereinafter
IndoProCaf) represents an effective antimigraine
drug available on the Italian market. The aim of this study was to test the efficacy of the three active principles alone and in combination in reverting
hyperalgesia.
Hyperalgesia was induced by
morphine withdrawal in mice treated with
morphine for 15 days and then made hyperalgic by
morphine substitution with water. This study showed that
indomethacin 0.3 mg kg(-1), i.p.;
caffeine 0.1 and 0.3 mg kg(-1), i.p.; and
prochlorperazine 0.1 mg kg(-1), i.p.; as well as the combination of the three active principles, were able to revert
morphine withdrawal induced
hyperalgesia, causing a statistically significant increase of pain threshold in hyperalgic mice. In a second model,
hyperalgesia was induced by the i.p. injection of a 0.3%
solution of
acetic acid in mice and was evaluated counting the number of abdominal constrictions.
Indomethacin (0.1 mg kg(-1), i.p.),
caffeine (0.3 mg kg(-1), i.p.), and
prochlorperazine (0.1 mg kg(-1), i.p.) reduced the number of abdominal constrictions, while the combination of the three active principles was able to abolish almost completely the abdominal constrictions, with a significantly higher efficacy compared to the single active principles. In both models,
indomethacin,
caffeine, and
prochlorperazine reverted
hyperalgesia at dosages 10 times lower than the corresponding
analgesic ones. These data provide the pharmacologic evidence of the efficacy of
IndoProCaf in reverting
hyperalgesia, a condition of reduction of pain threshold similar to that occurring in
migraine.