Abstract
Background: Acid-sensing ion channels (ASIC) contribute to acid-evoked pain in many painful inflammatory and ischemic conditions such as rheumatoid arthritis, cardiac ischemia, and exhausted skeletal muscles, which are accompanied by local tissue acidosis. Amiloride, a potassium-sparing diuretic was recently discovered to be a blocker of these ASIC.

Aims and Objectives: The objective of present study is to evaluate the analgesic activity of amiloride in chemically induced pain models of rats and mice and compare it against the standard analgesic aspirin.

Materials and Methods: A total of 24 mice and 24 rats were distributed into four groups of 6 each: Group A received distilled water as control, Group B received the test drug amiloride - low dose (20 mg/kg), Group C received amiloride-high dose (40 mg/kg), and Group D received standard drug aspirin (25 mg/kg); all drugs were given intraperitoneally. In formalin test, 0.025 ml of 1% formalin was injected under the plantar surface of hind paw and the mean time of paw licking (MTPL) was measured in both early (0-5 min) as well as late (20-40 min) phase. In acetic acidinduced writhing test, the animals were injected with 1 ml/100 g body weight of 0.6% acetic acid i.p. The number of writhings produced was recorded over a period of 20 min.

Results: In the early phase of formalin test, the MTPL was significantly reduced (P < 0.05) in Group B (30.2%) and in Group C (59.1%) and highly significantly reduced (P < 0.001) in Group D (74.6%) in mice, whereas in rats there was a significant reduction in MTPL in Group B (48.4%) only and a highly significant reduction was observed in both Group C (62.8%) and Group D (76.9%). In the late phase, in both mice and rats, there was a highly significant reduction in MTPL in all the 3 groups. In writhing test, the number of writhes have been reduced significantly from 51.17 ± 3.28 (mean ± standard error of mean) in Group A to 32.33 ± 3.67 in Group B and to 26.16 ± 3.98 in Group C and highly significantly to 12.17 ± 2.52 in Group D.

Conclusion: Amiloride showed a comparable but lower analgesic activity than aspirin in chemically induced pain models in rats and mice.

Key words: Acetic Acid-induced Writhing; Acid-sensing Ion Channels; Formalin Test; Mean Time of Paw Licking