Investigation of the antinociceptive effect of pregabalin in mice.

FS KILIC1, B KAYGISIZ1, N SENGULEROGLU1, C BAYDEMIR2, K EROL1. 1Eskisehir Osmangazi University Medical Faculty, Dept. of Pharmacology 26480, Turkey, 2Eskisehir Osmangazi University Medical Faculty, Dept. of Biostatistics 26480, Turkey

Objective: Pregabalin which is a congener of gabapentin, is used in the treatment of neuropathic pain syndromes. This study aims to investigate the central and peripheric antinociceptive effects of pregabalin and the contribution of nitrergic, serotonergic, opioidergic and arachidonergic pathways.

Materials and Methods: Male, Swiss albino mice (30-35g) were used (n=8 for all groups; total n=64). Pregabalin was administered at doses of 10, 30 and 100mg/kg. Saline was given to control group. Tail flick (central spinal level), tail clip (central spinal level) and hot plate (central supraspinal level) tests were used to investigate the central and 0,6% acetic acid induced writhing test was used to assess peripheric antinociceptive effects. In addition, pregabalin 100 mg/kg was combined with NG-nitro-L-arginine methyl ester (L-NAME) 100mg/kg, L-arginine 100mg/kg, cyproheptadine 50μg/kg and naloxone 1mg/kg. Statistical analysis was made by using Kruskal-wallis test.

Results: Pregabalin 100mg/kg statistically increased the percentage of maximal potent effect (% MPE) in tail flick and tail clip tests and decreased the number of writhings induced by acetic acid (p<0.05). Pregabalin made no alteration in hot plate test at all doses (p>0.05). The results of the combined use of pregabalin 100 mg/kg with L-NAME, L-arginine, cyproheptadine, and naloxone showed that % MPE was reduced only in the combination of pregabalin with L-NAME. This reduction was observed only in tail flick and tail clip tests.

Conclusion: We suggest that high dose pregabalin (100 mg/kg) presents central spinal and peripheric antinociceptive effects but do not possess a central supraspinal antinociceptive effect. We also suggest that only nitrergic pathway plays a role in the central spinal antinociceptive effect of pregabalin while opioidergic and serotonergic pathways are not involved in. Additionally, only arachidonergic pathway (peripheric antinociceptive action) is involved in the peripheral effect of pregabalin while opioidergic, serotonergic and nitrergic pathways do not play a role in this effect.