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PAIN MEDICINE

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

H. Ayben Korkmaz, MD^*, Fikret Maltepe, MD^*, Serhat Erbayraktar, MD, Osman Yilmaz, Merih Güray, MD, M. erefettin Canda, MD, Ali Günerli, MD^*, and Necati Gökmen, MD^*

Departments of *Anesthesiology and Reanimation, Neurosurgery,the Animal Research Center, and the Department of Pathology, Dokuz Eylül University, School of Medicine, zmir, Turkey

Address correspondence and reprint requests to Fikret Maltepe, MD, Dokuz Eylül Üniversitesi Tp Fakültesi, Anesteziyoloji ve Reanimasyon AD, 35340 INCIRALTI, IZMIR, TÜRKYE. Address email to fikret.maltepe{at}deu.edu.tr

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.

IMPLICATIONS: The present study is unique because it has demonstrated that chronic intrathecal administration of ketorolac tromethamine in rats, even at considerably large doses, showed a potent analgesic effect during the formalin test without exhibiting any neurotoxic side effect.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999