Buritova Jaroslava, Honoré Prisca, Chapman Victoria, Besson Jean-Marie
Unité de Recherches de Physiopharmacologie du Système Nerveux, INSERM U161 and EPHE, Paris, France.
Pain. 1996 Mar;64(3):559-568. doi: 10.1016/0304-3959(95)00167-0.
This study determines the effects of dexamethasone versus co-administered dexamethasone and diclofenac, on carrageenan-evoked spinal c-Fos expression and peripheral oedema in the freely moving rat. Drugs were administered intravenously 25 min before intraplantar injection of carrageenan (6 mg/150 microliters of saline). Three hours later the number of spinal c-Fos-LI neurones and peripheral oedema were assessed. The total number of control carrageenan-evoked c-Fos-LI neurones in the lumbar spinal cord was 121 +/- 5 labelled neurones per section, segments L4-L5, which were predominantly located in the superficial and deep laminae (41 +/- 3% and 40 +/- 2% of the total number of c-Fos-LI neurones per section, respectively) of the dorsal horn of the spinal cord. Pre-administered dexamethasone (0.05, 0.10 and 0.50 mg/kg i.v.) dose-dependently reduced the total number of c-Fos-LI neurones (30 +/- 4%, 52 +/- 3% and 58 +/- 2% reduction, respectively), with effects of the higher doses being strongest on the deep laminae c-Fos-LI neurones. The effects of dexamethasone on the total number of c-Fos-LI neurones and the peripheral oedema were positively correlated. Co-administration of low doses of dexamethasone and diclofenac (0.025 + 1.5 mg/kg i.v. respectively), which had negligible effects when administered separately, greatly reduced both the total number of carrageenan-evoked c-Fos-LI neurones (61 +/- 5% reduction as compared to control value) and the peripheral oedema (80 +/- 8% and 60 +/- 5% reduction for ankle and paw oedema, respectively). The attenuation by co-administered dexamethasone and diclofenac, of both c-Fos expression and the peripheral oedema, was significantly greater than the effect of dexamethasone alone (P < 0.001 for both) and diclofenac alone (P < 0.001 for both). Our study illustrates enhanced attenuating effects of co-administered dexamethasone and diclofenac on both inflammatory oedema and the associated spinal expression of c-Fos, an indicator of nociceptive transmission at the spinal level. The apparent interactions between the mechanisms of action of NSAIDs and steroids suggest that co-therapy may produce beneficial inflammatory and pain relief in the absence of excessive side effects.
本研究确定了地塞米松与联合使用地塞米松和双氯芬酸相比，对卡拉胶诱发的自由活动大鼠脊髓c-Fos表达和外周水肿的影响。在足底注射卡拉胶（6mg/150微升生理盐水）前25分钟静脉注射药物。3小时后，评估脊髓c-Fos免疫反应性（c-Fos-LI）神经元数量和外周水肿情况。对照组中，卡拉胶诱发的腰段脊髓（L4-L5节段）c-Fos-LI神经元总数为每节121±5个标记神经元，这些神经元主要位于脊髓背角的浅、深层（分别占每节c-Fos-LI神经元总数的41±3%和40±2%）。预先给予地塞米松（0.05、0.10和0.50mg/kg静脉注射）剂量依赖性地减少了c-Fos-LI神经元总数（分别减少30±4%、52±3%和58±2%），高剂量对深层c-Fos-LI神经元的作用最强。地塞米松对c-Fos-LI神经元总数和外周水肿的影响呈正相关。联合给予低剂量地塞米松和双氯芬酸（分别为0.025+1.5mg/kg静脉注射），单独给药时作用可忽略不计，但大大减少了卡拉胶诱发的c-Fos-LI神经元总数（与对照值相比减少61±5%）和外周水肿（踝关节和爪部水肿分别减少80±8%和60±5%）。联合使用地塞米松和双氯芬酸对c-Fos表达和外周水肿的减轻作用明显大于单独使用地塞米松（两者P均<0.001）和单独使用双氯芬酸（两者P均<0.001）。我们的研究表明，联合使用地塞米松和双氯芬酸对炎症性水肿和相关脊髓c-Fos表达（脊髓水平伤害性传递的指标）具有增强的减轻作用。非甾体抗炎药和类固醇作用机制之间明显的相互作用表明，联合治疗在无过多副作用的情况下可能产生有益的抗炎和止痛效果。
