Meymandi Manzumeh Shamsi, Keyhanfar Fariborz, Sepehri Gholam Reza, Heravi Gioia, Yazdanpanah Omid
Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
Pharmacology Department, Iran University of Medical Sciences, Tehran, Iran.
Anesth Pain Med. 2017 Jun 21;7(3):e14602. doi: 10.5812/aapm.14602. eCollection 2017 Jun.
Pregabalin has shown remarkable antinociceptive effects in neuropathic pain; however, its efficacy against acute and visceral pain remained controversial.
The present study aimed at investigating the involvement of N-methyl-D-aspartate (NMDA) receptors in the antinociceptive effect of pregabalin in both acute and visceral pain using and comparing hot plate test and writhing test in male mice.
NMDA (15 and 30 mg/kg), as an agonist or MK801 (0.02 and 0.05 mg/kg) as an NMDA receptor (NMDAR) antagonist, were injected intraperitoneally either alone or 15 minutes before a dose of pregabalin that produced almost 30% antinociception (100 mg/kg in hot plate test and 5 mg/kg in writhing tests). Then, the percentage of maximal possible effect (MPE%) at the 30th and 60th minutes in hot plate test and effect percentage (E%) in writhing test were measured and compared as antinociceptive indexes.
In hot plate test, pretreatment with MK801 (0.05 mg/kg) significantly increased antinociceptive effect of 100 mg/kg pregabalin, but pretreatment with NMDA did not result in any effect. Pretreatment with MK801 in writhing test significantly increased the antinociceptive effect of 5 mg/kg pregabalin (In contrast to 30 mg/kg NMDA that significantly decreased it.). NMDA induced antinociception reduction or MK801 increased antinociception in writhing test were significantly higher than what was observed in hot plate test.
Our results suggested that pregabalin antinociception in acute and visceral pain is mediated through NMDA receptors. Although this effect depends on the dose of NMDAR ligand, it is more pronounced in the behavioral response in the writhing test.
普瑞巴林在神经性疼痛中已显示出显著的抗伤害感受作用；然而，其对急性疼痛和内脏痛的疗效仍存在争议。
本研究旨在通过对雄性小鼠进行热板试验和扭体试验，研究N-甲基-D-天冬氨酸（NMDA）受体在普瑞巴林对急性疼痛和内脏痛的抗伤害感受作用中的参与情况，并进行比较。
单独腹腔注射NMDA（15毫克/千克和30毫克/千克）作为激动剂或MK801（0.02毫克/千克和0.05毫克/千克）作为NMDA受体（NMDAR）拮抗剂，或在产生近30%抗伤害感受的普瑞巴林剂量（热板试验中为100毫克/千克，扭体试验中为5毫克/千克）前15分钟注射。然后，测量并比较热板试验中第30分钟和第60分钟的最大可能效应百分比（MPE%）以及扭体试验中的效应百分比（E%），作为抗伤害感受指标。
在热板试验中，MK801（0.05毫克/千克）预处理显著增强了100毫克/千克普瑞巴林的抗伤害感受作用，但NMDA预处理未产生任何作用。扭体试验中MK801预处理显著增强了5毫克/千克普瑞巴林的抗伤害感受作用（与显著降低该作用的30毫克/千克NMDA相反）。扭体试验中NMDA诱导的抗伤害感受降低或MK801增强的抗伤害感受显著高于热板试验中的观察结果。
我们的结果表明，普瑞巴林对急性疼痛和内脏痛的抗伤害感受作用是通过NMDA受体介导的。虽然这种作用取决于NMDAR配体的剂量，但在扭体试验的行为反应中更为明显。
