Biomaterial Database

Cross-tolerance between spinal neostigmine and morphine in the rat. 2003

S A Dunbar, and I G Karamian

Department of Anesthesiology, Tufts University School of Medicine, Baystate Medical Center, Springfield, MA 01199, USA. Stuart.Dunbar@bhs.org

BACKGROUND Direct or indirect acting cholinergic muscarinic agonists such as neostigmine, are potent antinociceptives when administered intrathecally (i.t.). This study examines whether spinal neostigmine tolerance and cross-tolerance to spinal morphine occurs. METHODS Rats (32/group) were implanted with miniosmotic pumps delivering either i.t. saline 1 microl h(-1) (S), morphine 10 nmol microl(-1) h(-1) (M), or neostigmine 3 nmol microl(-1) h(-1) (N). Latencies (infrared thermal withdrawal rear paw) were measured daily for 6 days after which four animals from each group were given one i.t. challenge dose of morphine (m) 0.1, 1, 10, or 100 nmol, or neostigmine (n) 0.3, 3, 10, or 30 nmol. RESULTS Neostigmine and morphine-infused animals both developed tolerance to spinal neostigmine, but neostigmine-infused animals showed no significant cross-tolerance to spinal morphine; mean ED(50) nmol (CI 95%) dose-response values were Sn 2.6 (1.9-3.5), Mn 15.6 (9.9-24.6)*, Nn 18.7 (11.7-29.8)*, Sm 0.7 (0.4-1.1), Nm 1.2 (0.8-2.0), Mm 152 (50-461)* (*significance vs saline infused control group). CONCLUSIONS Thus, unidirectional cross-tolerance from morphine to neostigmine was evident. Previous studies suggest morphine has a cholinergic mechanism of action partially accounting for its antinociceptive effect, which may explain this observed unidirectional cross-tolerance.

UI	MeSH Term	Description	Entries
D007260	Infusion Pumps	Fluid propulsion systems driven mechanically, electrically, or osmotically that are used to inject (or infuse) over time agents into a patient or experimental animal; used routinely in hospitals to maintain a patent intravenous line, to administer antineoplastic agents and other drugs in thromboembolism, heart disease, diabetes mellitus (INSULIN INFUSION SYSTEMS is also available), and other disorders.	Drug Infusion Systems,Infusion Pump,Infusion Pumps, External,Infusors,Intravenous Drug Delivery System,Intravenous Drug Delivery Systems,Perfusion Pumps,Pumps, Infusion,Drug Infusion System,External Infusion Pump,External Infusion Pumps,Infusion Pump, External,Infusion System, Drug,Infusion Systems, Drug,Infusor,Perfusion Pump,Pump, External Infusion,Pump, Infusion,Pump, Perfusion,Pumps, External Infusion,Pumps, Perfusion,System, Drug Infusion,Systems, Drug Infusion
D007278	Injections, Spinal	Introduction of therapeutic agents into the spinal region using a needle and syringe.	Injections, Intraspinal,Injections, Intrathecal,Intraspinal Injections,Intrathecal Injections,Spinal Injections,Injection, Intraspinal,Injection, Intrathecal,Injection, Spinal,Intraspinal Injection,Intrathecal Injection,Spinal Injection
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
D009388	Neostigmine	A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.	Synstigmin,Neostigmine Bromide,Neostigmine Methylsulfate,Polstigmine,Proserine,Prostigmin,Prostigmine,Prozerin,Syntostigmine,Bromide, Neostigmine,Methylsulfate, Neostigmine
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
D002800	Cholinesterase Inhibitors	Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.	Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
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
D004334	Drug Administration Schedule	Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.	Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration