Department of Toxicology and Health Protection, Medical University of Silesia, Str Medyków 18, 40-752 Katowice, Poland.
Neurotox Res. 2013 Aug;24(2):258-64. doi: 10.1007/s12640-013-9385-4. Epub 2013 Mar 6.
The present study explored the antinociceptive effects of H₃ (R-methylhistamine) and GABA(B) (baclofen) receptor ligands in an orofacial model of pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (50 μl, 5 %) in the upper lip region, and the number of jumps and time spent face rubbing was recorded for 40 min. Formalin produced a marked biphasic pain response; first phase, 0-10 min (jumps), and second phase, 15-40 min, (rubbing). Baclofen (50 μg) injected into the rat wiskerpad 5 min before formalin administration suppressed both phases of pain whereas R-alpha-methylhistamine (12.5 μg) abolished the first phase only. Brains were taken immediately after behavioral testing was completed. HPLC/ED analysis showed that 5-hydroxytryptamine (5-HT) turnover was increased in hippocampus, thalamus, and brain stem of all formalin groups, excepting the baclofen group in which the balance of 5-HT metabolism was restored to control values. These findings demonstrate that GABA(B) receptors represent peripheral targets for analgesia. Consequently, locally administered baclofen may be a useful approach in treating inflammatory trigeminal pain.
本研究探讨了 H₃（R-甲基组氨酸）和 GABA（B）（巴氯芬）受体配体在大鼠口腔疼痛模型中的镇痛作用。口腔疼痛通过在上唇区域皮下注射福尔马林（50 μl，5%）诱导，记录 40 分钟内的跳跃次数和面部摩擦时间。福尔马林产生明显的双相疼痛反应；第一相，0-10 分钟（跳跃），第二相，15-40 分钟（摩擦）。巴氯芬（50 μg）在福尔马林给药前 5 分钟注入大鼠触须垫，可抑制两相间的疼痛，而 R-α-甲基组氨酸（12.5 μg）仅消除第一相。行为测试完成后立即取出大脑。HPLC/ED 分析显示，除巴氯芬组外，所有福尔马林组的海马体、丘脑和脑干中的 5-羟色胺（5-HT）转化率均增加，而巴氯芬组的 5-HT 代谢平衡恢复到对照值。这些发现表明 GABA（B）受体是外周镇痛的靶点。因此，局部给予巴氯芬可能是治疗炎症性三叉神经痛的一种有效方法。
