Buritova Jaroslava, Larrue Sonia, Aliaga Monique, Besson Jean-Marie, Colpaert Francis
Centre de Recherche Pierre Fabre, 17 avenue Jean Moulin, 81106 Castres, France.
Eur J Pharmacol. 2005 May 9;514(2-3):121-30. doi: 10.1016/j.ejphar.2005.03.016.
We studied the effects of the high-efficacy 5-hydroxytryptamine1A (5-HT1A) receptor agonist, F 13640 on both formalin-induced spinal cord c-Fos protein expression and pain behaviours in the rat. Replicating earlier data, F 13640 (0.63 mg/kg, i.p.; t(-15 min)) completely inhibited the elevation and licking of the formalin-injected paw. In the same animals, and in spite of the agent as in earlier data increasing the number of c-Fos labelled nuclei when it was administered alone, F 13640 markedly reduced the number of formalin-induced c-Fos labelled nuclei. This was found in both the superficial (I-II) and deep (V-VI) dorsal horn laminae (2 h post-injection: 72+/-2% and 92+/-1% of reduction, respectively; P<0.001 in either case), spinal areas that contain neurons responsive to nociceptive stimulation. Co-operation occurred so that after the co-administration of F 13640 and formalin, c-Fos expression was inferior to that induced when either stimulation was administered alone. The data provide initial evidence for the agent's inhibitory effects on noxiously evoked c-Fos expression. The results indicate that co-operation between 5-HT1A receptor activation and nociceptive stimulation powerfully inhibits responses to severe, tonic nociception.
我们研究了高效5-羟色胺1A（5-HT1A）受体激动剂F 13640对福尔马林诱导的大鼠脊髓c-Fos蛋白表达和疼痛行为的影响。重复早期数据，F 13640（0.63 mg/kg，腹腔注射；-15分钟）完全抑制了注射福尔马林爪子的抬高和舔舐。在同一批动物中，尽管与早期数据一样，该药物单独给药时会增加c-Fos标记细胞核的数量，但F 13640显著减少了福尔马林诱导的c-Fos标记细胞核的数量。在浅表（I-II）和深部（V-VI）背角层均发现了这种情况（注射后2小时：分别减少72±2%和92±1%；两种情况下P<0.001），这些脊髓区域含有对伤害性刺激有反应的神经元。存在协同作用，使得F 13640和福尔马林共同给药后，c-Fos表达低于单独给予任何一种刺激时诱导的表达。这些数据为该药物对伤害性诱发的c-Fos表达的抑制作用提供了初步证据。结果表明，5-HT1A受体激活与伤害性刺激之间的协同作用有力地抑制了对严重、持续性伤害性刺激的反应。
