Complete Prevention but Stimulus-dependent Reversion of Morphine Tolerance by the Glycine/NMDA Receptor Antagonist (+)-HA966 in Neuropathic Rats
| Autor: | Christensen D, Gisèle Guilbaud, Valérie Kayser |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class medicine.medical_treatment Pain Receptors N-Methyl-D-Aspartate Rats Sprague-Dawley Receptors Glycine Drug tolerance Internal medicine medicine Animals Saline Pain Measurement Behavior Animal Morphine business.industry Antagonist Peripheral Nervous System Diseases Drug Tolerance Receptor antagonist Pyrrolidinones Rats Analgesics Opioid Anesthesiology and Pain Medicine Endocrinology Injections Intravenous Neuropathic pain NMDA receptor Sciatic nerve business Excitatory Amino Acid Antagonists medicine.drug |
| Zdroj: | Anesthesiology. 92:786-794 |
| ISSN: | 0003-3022 |
| Popis: | Background Tolerance to the analgesic effect of morphine complicates the management of chronic pain states. The authors studied the ability of the glycine/N-methyl-D-aspartate receptor antagonist (+)-HA966 to modify morphine tolerance in a rat model of neuropathic pain. Methods Mononeuropathy was induced by placing four ligatures around the common sciatic nerve. The 4-day pretreatment regimens with two daily subcutaneous injections of saline and saline, saline and morphine (10 mg/kg), (+)-HA966 (2.5 mg/kg) and morphine, or (+)-HA966 and saline were begun on post-operative day 12 to test the ability of (+)-HA966 to prevent the development of tolerance. Behavioral experiments were performed on postoperative day 16, when the pain-related behavior reached a stable maximum. The effect of an acute dose of morphine (1 mg/kg intravenously) was tested against both mechanical (vocalization threshold to paw pressure) and thermal (struggle latency to hind paw immersion into a 46 degrees C hot-water bath) stimuli. In addition, to test the ability of a single injection of (+)-HA966 to reverse established morphine tolerance, groups of morphine-pretreated rats received injections of either (+)-HA966 (2.5 mg/kg subcutaneously) and morphine (1 mg/kg intravenously), saline and morphine, or (+)-HA966 and saline. Results Baseline vocalization thresholds and struggle latencies did not differ in the various pretreatment groups, indicating that the pretreatments had no effect on pain-related behavior. Coadministration of (+)-HA966 prevented the reduction of the effect observed with morphine alone in both the mechanical test and the thermal test. (+)-HA966 reversed morphine tolerance in the thermal but not in the mechanical test. Conclusion (+)-HA966 prevented morphine tolerance in both mechanical and thermal tests but reversed established morphine tolerance in the thermal test only. |
| Databáze: | OpenAIRE |
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