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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bell, A. Powell, K. J. Jhamandas, K. Hosokawa, A. Quirion, R. Sutak, M. Milne, B. |
| Description | Author Affiliation: Powell KJ ( Department of Pharmacology & Toxicology, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada.) |
| Abstract | 1. This study examined the effects of the COX inhibitors, ketorolac and ibuprofen, and the NOS inhibitor L-NAME for their potential to both inhibit the development and reverse tolerance to the antinociceptive action of morphine. 2. Repeated administration of intrathecal morphine (15 micrograms), once daily, resulted in a progressive decline of antinociceptive effect and an increase in the ED50 value in the tailflick and paw pressure tests. Co-administration of ketorolac (30 and 45 micrograms) or S(+) ibuprofen (10 micrograms) with morphine (15 micrograms) prevented the decline of antinociceptive effect and increase in ED50 value. Similar treatment with L-NAME (100 micrograms) exerted weaker effects. Administration of S(+) but not R(-) ibuprofen (10 mg kg-1) had similar effects on systemic administration of morphine (15 mg kg-1). 3. Intrathecal or systemic administration of the COX or NOS inhibitors did not alter the baseline responses in either tests. Acute keterolac or S(+) ibuprofen also did not potentiate the acute actions of spinal or systemic morphine, but chronic intrathecal administration of these agents increased the potency of acute morphine. 4. In animals already tolerant to intrathecal morphine, subsequent administration of ketorolac (30 micrograms) with morphine (15 micrograms) partially restored the antinociceptive effect and ED50 value of acute morphine, reflecting the reversal of tolerance. Intrathecal L-NAME (100 micrograms) exerted a weaker effect. 5. These data suggest that spinal COX activity, and to a lesser extent NOS activity, contributes to the development and expression of opioid tolerance. Inhibition of COX may represent a useful approach for the prevention as well as reversal of opioid tolerance. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 3 |
| Volume Number | 127 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-06-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Analgesics, Opioid Pharmacology Cyclooxygenase Inhibitors Enzyme Inhibitors Morphine Adverse Effects Nitric Oxide Synthase Antagonists & Inhibitors Animals Drug Tolerance Ibuprofen Injections, Intraperitoneal Injections, Spinal Ketorolac NG-Nitroarginine Methyl Ester Nociceptors Drug Effects Rats, Sprague-Dawley Spinal Cord Physiology Tolmetin Analogs & Derivatives Comparative Study Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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