Biomaterial Database

Antinociceptive effects of ketamine-opioid combinations in the mouse tail flick test. 1994

Y M Dambisya, and T L Lee

Department of Anaesthesia, National University of Singapore.

The antinociceptive activities of intraperitoneal (i.p.) ketamine in combination with subcutaneous (s.c.) morphine or fentanyl were studied using the mouse tail flick test, an acute pain model. Morphine and fentanyl exhibited dose-dependent effects, with respective ED50s (95% confidence limits) of 1.3 (1.2-1.4) mg/kg and 6.8 (6.2-7.4) mcg/kg. Ketamine (1, 5, 10 and 20 mg/kg) showed relatively weak antinociceptive effects with no apparent dose-response relationship. In mice pretreated with i.p. ketamine 0.1 mg/kg (no effect on the tail flick reaction time) and 1 mg/kg (antinociceptive), the effects of s.c. morphine (1.5 mg/kg) were enhanced but this was significant only at the higher ketamine dose, whereas fentanyl (6 mcg/kg, s.c.) antinociception was significantly enhanced in both pretreatment groups. The antinociceptive effects of i.p. ketamine (10 and 20 mg/kg) were also studied in mice pretreated with s.c. morphine 0.1 and 0.5 mg/kg or fentanyl 0.5 and 2.5 mcg/kg. Morphine dose-dependently enhanced ketamine antinociception, being significant only at the higher pretreatment dose level. Fentanyl (0.5 mcg/kg) pretreatment significantly enhanced ketamine (20 mg/kg) activity, with no apparent effect on ketamine 10 mg/kg. At 2.5 mcg/kg, fentanyl pretreatment significantly enhanced ketamine antinociception. These results suggest that ketamine may not be as effective in acute pain as opioids are, and that after systemic administration, the net effect of ketamine-opioid combination is a simple additive one.

UI	MeSH Term	Description	Entries
D007274	Injections, Intraperitoneal	Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.	Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007279	Injections, Subcutaneous	Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.	Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D007649	Ketamine	A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.	2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
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
D009294	Narcotics	Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.	Analgesics, Narcotic,Narcotic Analgesics,Narcotic,Narcotic Effect,Narcotic Effects,Effect, Narcotic,Effects, Narcotic
D010147	Pain Measurement	Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.	Analgesia Tests,Analogue Pain Scale,Formalin Test,McGill Pain Questionnaire,Nociception Tests,Pain Assessment,Pain Intensity,Pain Severity,Tourniquet Pain Test,Visual Analogue Pain Scale,Analog Pain Scale,Assessment, Pain,McGill Pain Scale,Visual Analog Pain Scale,Analgesia Test,Analog Pain Scales,Analogue Pain Scales,Formalin Tests,Intensity, Pain,Measurement, Pain,Nociception Test,Pain Assessments,Pain Intensities,Pain Measurements,Pain Questionnaire, McGill,Pain Scale, Analog,Pain Scale, Analogue,Pain Scale, McGill,Pain Severities,Pain Test, Tourniquet,Questionnaire, McGill Pain,Scale, Analog Pain,Scale, Analogue Pain,Scale, McGill Pain,Severity, Pain,Test, Analgesia,Test, Formalin,Test, Nociception,Test, Tourniquet Pain,Tests, Nociception,Tourniquet Pain Tests
D011930	Reaction Time	The time from the onset of a stimulus until a response is observed.	Response Latency,Response Speed,Response Time,Latency, Response,Reaction Times,Response Latencies,Response Times,Speed, Response,Speeds, Response
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug