Cyclooxygenase-2 inhibition potentiates morphine antinociception at the spinal level in a postoperative pain model
| Autor: | Kenneth J. Tuman, Jeffrey S. Kroin, Robert J. McCarthy, Hila Hemmati, Asokumar Buvanendran |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Pain Threshold Injections Subcutaneous Postoperative pain Rats Sprague-Dawley Animals Medicine Cyclooxygenase Inhibitors Injections Spinal Pain Measurement Pain Postoperative Behavior Animal Cyclooxygenase 2 Inhibitors Dose-Response Relationship Drug Morphine biology business.industry Drug Synergism General Medicine Spinal cord Rats Peripheral Analgesics Opioid Isoenzymes Anesthesiology and Pain Medicine Allodynia medicine.anatomical_structure Spinal Cord Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Anesthesia Indans Hyperalgesia biology.protein Cyclooxygenase Opiate medicine.symptom business medicine.drug |
| Zdroj: | Regional Anesthesia and Pain Medicine. 27:451-455 |
| ISSN: | 1098-7339 |
| DOI: | 10.1053/rapm.2002.35521 |
| Popis: | Background and Objectives After peripheral inflammatory stimuli, spinal cord cyclooyxgenase-2 (COX-2) mRNA and protein levels increase, whereas COX-1 is unchanged. In animal models of inflammatory pain, intrathecal COX-2 selective inhibitors suppress hyperalgesia. However, the role of spinal COX-2 inhibition in postoperative pain is not well elucidated. This study investigates whether a water-soluble COX-2 selective inhibitor, L-745,337, can modify allodynic responses in a rat model of postoperative pain. Methods Allodynia was induced in the left plantar hindpaw by surgical incision. Animals then received intrathecal (0-80 μg) or subcutaneous (0-30 mg/kg) L-745,337 coadministered with intrathecal morphine (0-2 nmol). Reduction of mechanical allodynia (increased withdrawal threshold) was quantified with calibrated von Frey hairs. Results L-745,337 alone, whether intrathecal or systemic, had no effect on withdrawal threshold. When intrathecal L-745,337 at doses of 40 to 80 μg was combined with a subthreshold dose (0.5 nmol) of morphine, withdrawal thresholds were increased in a dose-dependent manner. Adding 80 μg L-745,337 to 1 nmol morphine produced an antiallodynic effect greater than that of morphine at twice the dose. Subcutaneous L-745,337, up to 30 mg/kg combined with intrathecal morphine resulted in the same antiallodynic response as morphine alone. Conclusion These results suggest a spinal interaction of COX-2 inhibition with opiate analgesia may allow a reduction of postoperative pain with lower doses of opiate. |
| Databáze: | OpenAIRE |
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