Biomaterial Database

Spinal cord morphology and antinociception after chronic intrathecal administration of excitatory amino acid antagonists in the rat. 1993

Jens D Kristensen, and Claes Post, and Torsten Gordh, and Björn A Svensson

Department of Anaesthesiology, University Hospital, S-751 85 UppsalaSweden Department of Pharmacology, Uppsala University, UppsalaSweden Department of Anatomy, Uppsala University, UppsalaSweden.

Drugs that antagonize the action of excitatory amino acids on the NMDA receptor in the spinal cord are of interest in pain treatment. Before such drugs can be applied clinically, their potential toxicity should be studied. This study was performed in rats in order to reveal possible neurotoxicologic side effects following chronic intrathecal (i.t.) application of two NMDA receptor antagonists: 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and kynurenic acid (KYN). Rats equipped with i.t. catheters were injected twice a day for 2 weeks with saline, 2 nmol (0.5 micrograms) CPP or 210 nmol (40 micrograms) KYN, where the doses of CPP and KYN were chosen on the basis of similar analgesic effects after one administration. Antinociception was tested daily using the tail-flick and hot-plate tests. The antinociceptive effect was similar in CPP- and KYN-treated rats on days 1 and 2. The effect of CPP decreased during the following days, whereas that of KYN persisted for the 12-day testing period. The spinal cord was then removed and prepared for light and electron microscopic examination, and a morphometric method using an unbiased stereological estimator of cell number and cell volume was applied as a sensitive variable of spinal cord neurotoxicity. Morphologic and ultrastructural analyses of the spinal cord segment adjacent to the tip of the catheter showed normal appearance with no differences between the groups. Furthermore, no differences in cell number or cell volume in the dorsal horn were found between the groups. In conclusion, chronic i.t. administration of pharmacologically active doses of CPP and KYN in rats did not produce neurotoxic effects in the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
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
D007736	Kynurenic Acid	A broad-spectrum excitatory amino acid antagonist used as a research tool.	Kynurenate,Acid, Kynurenic
D008297	Male		Males
D008854	Microscopy, Electron	Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.	Electron Microscopy
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
D010879	Piperazines	Compounds that are derived from PIPERAZINE.
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
D006358	Hot Temperature	Presence of warmth or heat or a temperature notably higher than an accustomed norm.	Heat,Hot Temperatures,Temperature, Hot,Temperatures, Hot
D000596	Amino Acids	Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.	Amino Acid,Acid, Amino,Acids, Amino
D000700	Analgesics	Compounds capable of relieving pain without the loss of CONSCIOUSNESS.	Analgesic,Anodynes,Antinociceptive Agents,Analgesic Agents,Analgesic Drugs,Agents, Analgesic,Agents, Antinociceptive,Drugs, Analgesic