Antinociceptive and neurotoxicologic screening of chronic intrathecal administration of ketorolac tromethamine in the rat.

Korkmaz H., Maltepe F., Erbayraktar S., Yilmaz O., Guray M., Canda M., ...More

Anesthesia and analgesia, vol.98, no.1, pp.148-152, 2004 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 98 Issue: 1
  • Publication Date: 2004
  • Doi Number: 10.1213/01.ane.0000093226.75543.90
  • Journal Name: Anesthesia and analgesia
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.148-152
  • Dokuz Eylül University Affiliated: Yes


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 muL of saline, and the other groups received 50,150, and 400 mug 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 mug 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.