• Natalia Sevostianova, Edwin Zvartau, Anton Bespalov, and Wojciech Danysz.
• 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.

AbstractThis 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.

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