Analgesic effects of peripherally administered opioids in clinical models of acute and chronic inflammation

• Published in: Clinical pharmacology and therapeutics Vol. 70; no. 1; pp. 66 - 73
• Main Authors: Dionne, Raymond A., Lepinski, Allen M., Gordon, Sharon M., Jaber, Louay, Brahim, Jaime S., Hargreaves, Kenneth M.
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01-07-2001
• Subjects: Acute Disease; Adult; Analgesics; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacology; Biological and medical sciences; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fentanyl - pharmacology; Humans; Injections; Male; Medical sciences; Mepivacaine - pharmacology; Morphine - pharmacology; Naloxone - pharmacology; Neuropharmacology; Pain Measurement; Pain, Postoperative - drug therapy; Pain, Postoperative - etiology; Periodontitis - complications; Pharmacology. Drug treatments; Time Factors; Tooth Extraction - adverse effects; Toothache - drug therapy; Toothache - etiology; Treatment Outcome; Human; Postoperative; Narcotic antagonist; Acute; Dental disease; Fentanyl; Morphine; Opiates; Inflammation; Narcotic analgesic; Site of action; Analgesia; Local administration; Chemotherapy; Chronic; Reversion; Pain; Naloxone; Treatment; Surgery; Tooth; Mechanism of action
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1067/mcp.2001.116443

A series of double‐blind, placebo‐controlled clinical trials demonstrated that low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the intraligamentary space of a chronically inflamed hyperalgesic tooth produced a dose‐related naloxone‐reversible analgesia. This analgesic effect is mediated by a local mechanism in the inflamed tissue, because subcutaneous administration of a 1.2 mg dose of morphine failed to elicit an analgesic response. In contrast, submucosal administration of 1.2 mg morphine or 50 μg fentanyl to the site of extraction of an impacted third molar after the onset of acute pain failed to elicit an analgesic response despite demonstration of a sensitive bioassay. These data indicate that peripheral opioid analgesia can be evoked in a model of chronic, but not acute, inflammatory pain, suggesting a temporal dependent mechanism needed for the expression of peripheral opiate analgesia during inflammation in humans.
Clinical Pharmacology & Therapeutics (2001) 70, 66–73; doi: 10.1067/mcp.2001.116443