The antinociceptive effect and mechanisms of action of pregabalin in mice

BackgroundPregabalin, a potent anticonvulsant agent, is used in treatment-resistant epileptic patients. It is reported that pregabalin also has analgesic effect in different pain syndromes. However, there is limited data on its antinociceptive mechanisms of action. We aimed to investigate the central and peripheral antinociceptive effects of pregabalin and the contribution of nitrergic, serotonergic, and opioidergic pathways in mice.MethodsWe used tail flick, tail clip and hot plate tests to investigate the central antinociceptive effects and acetic acid-induced writhing test to assess peripheral antinociceptive effects of pregabalin (10, 30, 100 mg/kg). We also combined pregabalin (100 mg/kg) with, a nonspecific nitric oxide synthase inhibitor l-NAME (100 mg/kg), a serotonin receptor antagonist cyproheptadine (50 μg/kg), and an opioid receptor antagonist naloxone (1 mg/kg).ResultsPregabalin 30 mg/kg enhanced the percentage of maximal possible effect (% MPE) in tail flick test. Pregabalin 100 mg/kg significantly increased % MPE in tail clip and tail flick tests and decreased the number of writhings. Pregabalin made no significant alteration in hot plate test at all doses. The combined use of pregabalin 100 mg/kg with l-NAME, cyproheptadine, and naloxone showed that % MPE was reduced only in the combination of pregabalin with naloxone and solely in tail clip test while no significant difference was observed in writhing test.ConclusionsWe suggest that pregabalin (30 and 100 mg/kg) presents central spinal but not central supraspinal antinociceptive effect and pregabalin 100 mg/kg shows peripheral antinociceptive effect. The opioidergic pathway seems to mediate the central spinal antinociceptive effect of pregabalin while nitrergic and serotonergic pathways are not involved.