Kaygisiz Bilgin, Kilic Fatma Sultan, Senguleroglu Nuri, Baydemir Canan, Erol Kevser
Eskişehir Osmangazi University, Medical Faculty, Department of Pharmacology, Meselik Kampusu, Eskisehir, Turkey.
Eskişehir Osmangazi University, Medical Faculty, Department of Pharmacology, Meselik Kampusu, Eskisehir, Turkey.
Pharmacol Rep. 2015 Feb;67(1):129-33. doi: 10.1016/j.pharep.2014.08.013. Epub 2014 Aug 27.
Pregabalin, 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.
We 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, 100mg/kg). We also combined pregabalin (100mg/kg) with, a nonspecific nitric oxide synthase inhibitor l-NAME (100mg/kg), a serotonin receptor antagonist cyproheptadine (50 μg/kg), and an opioid receptor antagonist naloxone (1mg/kg).
Pregabalin 30 mg/kg enhanced the percentage of maximal possible effect (% MPE) in tail flick test. Pregabalin 100mg/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 100mg/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.
We suggest that pregabalin (30 and 100mg/kg) presents central spinal but not central supraspinal antinociceptive effect and pregabalin 100mg/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.
普瑞巴林是一种强效抗惊厥药物，用于治疗难治性癫痫患者。据报道，普瑞巴林在不同疼痛综合征中也具有镇痛作用。然而，关于其抗伤害感受作用机制的数据有限。我们旨在研究普瑞巴林对小鼠的中枢和外周抗伤害感受作用以及一氧化氮能、5-羟色胺能和阿片样物质能途径的作用。
我们使用甩尾、夹尾和热板试验来研究普瑞巴林（10、30、100mg/kg）的中枢抗伤害感受作用，并使用醋酸诱导扭体试验来评估其外周抗伤害感受作用。我们还将普瑞巴林（100mg/kg）与非特异性一氧化氮合酶抑制剂L-NAME（100mg/kg）、5-羟色胺受体拮抗剂赛庚啶（50μg/kg）和阿片受体拮抗剂纳洛酮（1mg/kg）联合使用。
30mg/kg的普瑞巴林提高了甩尾试验中的最大可能效应百分比（%MPE）。100mg/kg的普瑞巴林在夹尾和甩尾试验中显著增加了%MPE，并减少了扭体次数。所有剂量的普瑞巴林在热板试验中均未产生显著变化。100mg/kg的普瑞巴林与L-NAME、赛庚啶和纳洛酮联合使用表明，仅在普瑞巴林与纳洛酮联合使用时，%MPE在夹尾试验中降低，而在扭体试验中未观察到显著差异。
我们认为普瑞巴林（30和100mg/kg）具有中枢脊髓而非中枢脊髓以上的抗伤害感受作用，100mg/kg的普瑞巴林具有外周抗伤害感受作用。阿片样物质能途径似乎介导了普瑞巴林的中枢脊髓抗伤害感受作用，而一氧化氮能和5-羟色胺能途径未参与其中。
