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Updated: Aug 11, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Interaction between calcium channel blockers and sweetening agents on morphine-induced analgesia in mice by formalin
S Nikfar1, M Abdollahi, F Sarkarati
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran.
Abstract:
1. Calcium is known to be an important ion in the modulation of nociception and inflammation. Previous research has shown that mice drinking sweet-tasting solutions such as sucrose, saccharin and aspartame exhibit significant changes in morphine-induced analgesia in both phases of the formalin test. 2. In this study, the role of calcium channel blockers on the effectivity of a 12-day regimen of different sweetening agents (sucrose 32%, saccharin 0.08% and aspartame 0.16%) on the alteration of the morphine response has been investigated. 3. Male albino mice weighing 20-27 g were used for experiments. Animals were given 12 days to adapt to dietary conditions. Animals were given morphine (1.5, 3, 6, 9 mg/kg) subcutaneously 30 min before observation. Nifedipine (5 mg/kg), verapamil (5 mg/kg) and diltiazem (10 mg/kg) were administered intraperitoneally 20 min before morphine injection. 4. Recording of the early phase started immediately and lasted for 10 min after formalin injection. Recording of the late response started 20 min after formalin injection and lasted for 10 min. 5. Calcium channel blockers potentiated the antinociceptive effects of sweetening agents and diminished the antagonistic effects of these compounds on morphine-induced analgesia in the early and late phases of the formalin test. 6. It is proposed that calcium has a role for the interactive effects of sweetening agents and morphine on pain sensitivity.

