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Problem statement: The present study was performed to determine the effect of Intracerebroventricular (ICV) administration of W-7, a specific calmodulin inhibitor, on the analgesic effect and development of tolerance to antinociceptive effect of acute and chronic morphine administration respectively. Approach: This study was carried out on male wistar rats, weighing 200-250 g. For acute experimental protocol, Morphine was injected intraperitonealy in a single dose (5 mg kg-1). For chronic experimental protocol, Morphine was administered daily (15 mg kg-1 for 8 days). The threshold to thermal nociceptive stimuli was measured by tail-flick test. In acute and chronic experiments, W-7 (0.25, 0.5 and 1 μmol/rat) was injected through ICV at different paradigms. Maximal Possible Effect percentage (MPE%) was considered as analgesia index. Results: Our result showed that W-7 (0.25, 0.5 and 1 μmol/rat) injections before acute morphine administration significantly reduced the analgesic effect of morphine compared with morphine treated group (all p

The present study was performed to determine the effect of intracerebroventricular (ICV) administration of W-7, a specific calmodulin inhibitor, on the development of tolerance to antinociceptive effect morphine administration. This study was carried out on male wistar rats, weighing 200-250 g. Morphine was administered daily (15 mg/kg for 8 days). The threshold to thermal nociceptive stimuli was measured by tail-flick test. W-7 (0.25, 0.5 and 1 micromol/rat) was injected through ICV. Maximal possible effect percentage (MPE %) was considered as analgesia index. Our result showed that chronic morphine exposure induced tolerance to its antinociceptive effect and administration of W-7 (0.5 and 1 micromol/rat) decreased the development of tolerance to it. In conclusion these data showed that chronic injection of W-7 inhibited the development of morphine tolerance which indicates that calmodulin and its dependent pathways may play a role in the morphine tolerance processes.

The aim of present study was to investigate the effect of trifluoperazine (TFP) on carrageenan-induced rat's paw edema in intact and adrenalectomized (ADX). TFP (0.2 and 8 mg/kg) were given intraperitoneally just before the intraplantar injection of 0.1 ml of 0.5% carrageenan solution. After four hours, paw edema was assessed by calculating the paw volume changes and extravasations of Evans blue dye as inflammatory indicators. In both ADX and control groups, administration of TFP reduced inflammatory parameters (paw volume and tissue content of Evans blue dye) in inflamed paw. Our findings suggest that TFP can effectively reduce carrageenan-induced paw edema in both ADX and control rats. Therefore, anti-inflammatory effect of these drugs does not need the adrenal gland activity.

The aim of present study was to investigate the effect of W-7, a calmodulin antagonist, on carrageenan-induced rat's paw edema. W-7(50 microMol/kg) was given intraperitoneally synchronous with the intraplantar injection of 0.1 ml of 0.5% carrageenan solution. After four hours, paw edema was assessed by calculating the paw volume changes which measured by hydroplethysmometer. In adrenalectomized rats, both adrenal glands were removed. Treatment of animals with W-7 reduced carrageenan-induced paw edema by 50%. In adrenalectomized rats, W-7 was also effective in reduction of paw edema (52%). There was no significant difference between the effect of W-7 in adrenalectomized and control animals. Our findings suggest that W-7 as a calmodulin inhibitor reduce carrageenan-induced paw edema and the inhibitory effect of W-7 on edema formation appears not to be dependent on adrenal function.