Morphine-induced analgesia in the hot-plate test: comparison between NMRI(nu/nu) and NMRI mice. 2004

Hilde Vermeirsch, and Theo F Meert
CNS Pain&Alzheimer, J&J Pharmaceutical Research and Development, Turnhoutseweg 30, B-2340 Beerse, Belgium. hvermeir@prdbe.jnj.com

NMRInu/nu mice are frequently used in cancer research, but their use in behavioural pain tests is unexplored. As behaviour of NMRI mice in pain tests is well-documented, a hot-plate test was performed comparing acute thermal nociception in NMRInu/nu and NMRI mice - untreated and morphine-treated - to estimate the usefulness of NMRInu/nu mice for further research on cancer pain. In both strains, morphine dose-dependently increased response latencies, number of animals reaching cut-off times and AUC values. Yet in NMRInu/nu mice, as compared to NMRI mice, all curves were shifted to the right. In order to be comparable, cut-off times must express a similar degree of baseline response augmentations. NMRInu/nu mice had substantially lower pre-drug latencies, indicating a lowered threshold for painful thermal stimuli, therefore effects of morphine in NMRInu/nu mice were also analysed using a lower cut-off time. Doing so, morphine resulted in similar effects in both strains. The effects were independent of hot-plate temperature, because similar results were obtained using temperatures of 50 and 55 degrees. The different morphine sensitivity of NMRInu/nu compared to NMRI mice primarily seems to depend upon differences in thermal threshold, probably induced by the different genotype of both strains. To determine whether cancer alters pain threshold or morphine analgesia, LoVo tumour-bearing NMRInu/nu mice were also tested. The tumour presence had no influence on withdrawal latencies or morphine efficacy. In general it can be concluded that NMRInu/nu mice with or without tumour can be used for nociceptive testing if baseline sensitivity is properly defined.

UI MeSH Term Description Entries
D008297 Male Males
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009374 Neoplasms, Experimental Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms. Experimental Neoplasms,Experimental Neoplasm,Neoplasm, Experimental
D010146 Pain An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS. Suffering, Physical,Ache,Pain, Burning,Pain, Crushing,Pain, Migratory,Pain, Radiating,Pain, Splitting,Aches,Burning Pain,Burning Pains,Crushing Pain,Crushing Pains,Migratory Pain,Migratory Pains,Pains, Burning,Pains, Crushing,Pains, Migratory,Pains, Radiating,Pains, Splitting,Physical Suffering,Physical Sufferings,Radiating Pain,Radiating Pains,Splitting Pain,Splitting Pains,Sufferings, Physical
D000698 Analgesia Methods of PAIN relief that may be used with or in place of ANALGESICS. Analgesias
D000701 Analgesics, Opioid Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Opioid,Opioid Analgesic,Opioid Analgesics,Opioids,Full Opioid Agonists,Opioid Full Agonists,Opioid Mixed Agonist-Antagonists,Opioid Partial Agonists,Partial Opioid Agonists,Agonist-Antagonists, Opioid Mixed,Agonists, Full Opioid,Agonists, Opioid Full,Agonists, Opioid Partial,Agonists, Partial Opioid,Analgesic, Opioid,Full Agonists, Opioid,Mixed Agonist-Antagonists, Opioid,Opioid Agonists, Full,Opioid Agonists, Partial,Opioid Mixed Agonist Antagonists,Partial Agonists, Opioid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013045 Species Specificity The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species. Species Specificities,Specificities, Species,Specificity, Species
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D019540 Area Under Curve A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992) AUC,Area Under Curves,Curve, Area Under,Curves, Area Under,Under Curve, Area,Under Curves, Area

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