Sevostianova Natalia, Zvartau Edwin, Bespalov Anton, Danysz Wojciech
Preclinical R&D, Merz Pharmaceuticals GmbH, Eckenheimer Landstrasse 100, 60318 Frankfort on the Main, Germany.
Eur J Pharmacol. 2003 Feb 21;462(1-3):109-13. doi: 10.1016/s0014-2999(03)01345-1.
This study focused on the antinociceptive action of morphine in the formalin test in rats. Formalin-induced behaviour is characterised by two phases relevant to acute and tonic pain. Morphine (1-6 mg/kg) was administered systemically before or after the early phase, and its ability to affect the late phase was investigated. Inhibitory effects of morphine (3 mg/kg) injected immediately after the early phase were significantly stronger (32+/-9%) compared to the preemptive administration (84+/-29%, relative to saline-treated controls, 5% formaldehyde). It appears that some neural and/or behavioural changes during the early phase limit effects of morphine on the late phase. Furthermore, manipulation of stimulation intensity (2% vs. 5% formaldehyde) significantly affected the ability of morphine (3 mg/kg) to suppress early (55+/-7% and 76+/-10%, respectively) but not late phase of formalin-induced behaviours. These results agree with the previous demonstrations on the effects of acute nociceptive stimulation intensity on analgesic potency of opiate drugs. Thus, the present study revealed two factors that affect the potency of morphine in formalin test: administration regimen and formalin concentration.
本研究聚焦于吗啡在大鼠福尔马林试验中的抗伤害感受作用。福尔马林诱导的行为具有与急性疼痛和持续性疼痛相关的两个阶段。在早期阶段之前或之后全身给予吗啡(1 - 6毫克/千克),并研究其对晚期阶段的影响能力。与预先给药(相对于生理盐水处理的对照组,84±29%,5%甲醛)相比,在早期阶段后立即注射的吗啡(3毫克/千克)的抑制作用明显更强(32±9%)。似乎早期阶段的一些神经和/或行为变化限制了吗啡对晚期阶段的影响。此外,刺激强度的改变(2%与5%甲醛)显著影响了吗啡(3毫克/千克)抑制福尔马林诱导行为早期阶段(分别为55±7%和76±10%)的能力,但对晚期阶段没有影响。这些结果与先前关于急性伤害性刺激强度对阿片类药物镇痛效力影响的证明一致。因此,本研究揭示了影响吗啡在福尔马林试验中效力的两个因素:给药方案和福尔马林浓度。