Dopamine release is involved in antinociceptive effect of theophylline

The methylxanthines, e.g., theophylline, are widely used for the treatment of bronchial asthma. Additionally, a pain relieving effect of theophylline has been reported in patients as well as in experimental animals. The mechanism of this antinociceptive action is not clear. In this study, involvement of dopaminergic system in theophylline-induced antinociception was evaluated using tail flick test model. Swiss albino mice, (either sex, weighing 25-30 g) with base line tail flick latencies (TFL) between 2.0 and 3.5 s, were used. TFL was recorded before and at intervals of 15, 30, 45, and 60 min. after drug treatment. The experimental protocol was duly approved by the Institutional Animal Ethics Committee, All India Institute of Medical Sciences, New Delhi, India. To determine the role of dopaminergic system, the mice were pretreated with either D1 or D2 dopaminergic receptor antagonists SCH 23390 and haloperidol, respectively, prior to treatment with theophylline. Another group of animals received apomorphine along with theophylline. The dose of theophylline used, i.e., 10 mg/kg, intraperitoneally (i.p.), had shown a significant increase in TFLs. The theophylline-induced antinociception, 10 mg/kg, i.p., was reversed by pretreatment with both D1 and D2 dopaminergic receptor antagonists SCH 23390 and haloperidol as well as with apomorphine (1 mg/kg) pretreatment. The results suggest that theophylline-induced antinociception is due to release of dopamine.