Antinociceptive and Neurotoxicologic Screening of Chronic Intrathecal Administration of Ketorolac Tromethamine in the Rat

Many drugs are tested intrathecally to investigate alternatives to opioids. We aimed to explore the analgesic and possible neurotoxic effects of chronic intrathecally-administered ketorolac tromethamine in rats. Catheters were placed via atlantoaxial interval in 28 Wistar rats under anesthesia of in...

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Bibliographic Details
Published in:	Anesthesia and analgesia Vol. 98; no. 1; pp. 148 - 152
Main Authors:	Korkmaz, H. Ayben, Maltepe, Fikret, Erbayraktar, Serhat, Yilmaz, Osman, Güray, Merih, Canda, M. Şerefettin, Günerli, Ali, Gökmen, Necati
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD International Anesthesia Research Society 01-01-2004 Lippincott
Subjects:	Analgesics Anesthesia Anesthesia, General Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - pharmacology Anti-Inflammatory Agents, Non-Steroidal - toxicity Behavior, Animal - drug effects Biological and medical sciences Dose-Response Relationship, Drug Formaldehyde Injections, Spinal Ketorolac Tromethamine - administration & dosage Ketorolac Tromethamine - pharmacology Ketorolac Tromethamine - toxicity Male Medical sciences Neurons - pathology Neurotoxicity Syndromes - pathology Neurotoxicity Syndromes - physiopathology Pain Measurement - drug effects Rats Rats, Wistar Reaction Time - drug effects Reflex - drug effects Spinal Cord - pathology Rat Ketorolac Rodentia Medical screening Intrathecal administration Non steroidal antiinflammatory agent Vertebrata Chronic Trometamol Mammalia Analgesic Animal Osmotic diuretic Antipyretic Anesthesia
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Summary:	Many drugs are tested intrathecally to investigate alternatives to opioids. We aimed to explore the analgesic and possible neurotoxic effects of chronic intrathecally-administered ketorolac tromethamine in rats. Catheters were placed via atlantoaxial interval in 28 Wistar rats under anesthesia of intraperitoneally-injected thiopental 30 mg/kg. Rats were randomized into 4 groups and administered 4 repeated intrathecal doses of therapy with 5-day intervals. The control group received 10 μL of saline, and the other groups received 50, 150, and 400 μg of ketorolac tromethamine respectively. The formalin test, behavioral test, and histopathological examination of four different spinal cord levels were performed. Neither behavioral testing nor histopathological examination revealed abnormalities that would suggest neurotoxicity. Formalin tests showed that both phase I and phase II responses of ketorolac tromethamine groups were significantly less than those of the control group. Although phase I responses did not differ during comparisons among ketorolac tromethamine-administered groups, phase II responses decreased significantly in groups that received 150 and 400 μg of ketorolac tromethamine. Intrathecally administered ketorolac tromethamine reduced nociceptive responses and exhibited no untoward neurological effect even at large doses. However, its intrathecal use as a safe alternative drug for chronic pain remains to be investigated in other species.
ISSN:	0003-2999 1526-7598
DOI:	10.1213/01.ANE.0000093226.75543.90