Effect of dihydropyridine calcium channel blockers on formalin-induced pain response in mice

Voltage-gated calcium channels play a major role to control cellular processes in cardiac, vascular and neuronal tissues. Nimodipine, nifedipine and amlodipine are dihydropyridine calcium channel blockers widely used in cardiovascular ailments in humans. A number of studies have shown that calcium channel blockers have antinociception and antiinflammatory effects in a range of (but not all) animal models. The aim of this study was to investigate the effect of nimodipine, amlodipine and nifedipine on formalin-induced pain and inflammatory in mice. In this experimental study, 60 male NMRI mice (25-30 gr) were used. Nimodipine, nifedipine and amlodipine (10 mg/kg, single dose) were intraperitonealy injected 30 minutes before intrapawley formalin (5%, 20µl) injection. The time of licking and biting of injected paw was measured as pain response at 5 minutes intervals for  hour. The results showed that formalin induced a biphasic pain response (p<0.05), (first phase: 0-5 and second phase: 20-45 minute after injection). Intraperitoneal injection of nimodipine, nifedipine and amlodipine before formalin reduced the second phase (inflammatory pain) of pain response significantly (p<0.05) and only nimodipine reduced the first phase (neurogenic pain) of pain response significantly (p<0.05). The results suggested that the nimodipine, nifedipine and amlodipine have antinociceptive activity while only nimodipine reduced the neurogenic pain. These effects are probably via a decrease in calcium influx that in turn interferes with the release of neurotransmitters and other substances promoting nociception and inflammation.