Analysis of the Analgesic Effect of Locally Versus Systemically Administered Morphine in Rats.

Abstract

BACKGROUND: Pain management remains a critical challenge in medical practice. There is a complex interplay between chronic pain and opioid use disorder, 2 prevalent problems of significant public health concern. Research into new treatment strategies is increasingly important. STUDY QUESTION: This study aims to highlight the analgesic effect of morphine through its exclusive action on peripheral opioid receptors in carrageenan-induced inflammatory pain. STUDY DESIGN: The first experiment aimed to establish a dose-effect relationship for intraplantar morphine administration in a rat model of carrageenan-induced inflammation by testing successive doses after carrageenan injection. The second experiment assessed whether a 5-mg/kg dose of intraplantar morphine has only local, not central nervous system, analgesic effects by comparing it with 5- and 10-mg/kg doses given intraperitoneally. MEASURES AND OUTCOMES: For each rat, paw pain sensitivity was measured using the Ugo Basile Plantar Test-Hargreaves Apparatus. RESULTS: In the first part, lower doses (2.5 mg/kg) did not significantly affect paw withdrawal latency, whereas higher doses (5 and 10 mg/kg) increased it significantly, suggesting maximum receptor activation at 5 mg/kg intraplantarly. The 20-mg/kg intraplantar dose caused central nervous system effects, indicating systemic absorption. The second part compared intraplantar versus intraperitoneal morphine, finding that the 5-mg/kg intraplantar dose produced significant local analgesia, whereas the same intraperitoneal dose did not-supporting peripheral receptor involvement. CONCLUSIONS: Our findings suggest that morphine administered locally in experimentally inflamed tissue acts predominantly via peripheral opioid receptors. This opens the possibility for developing localized opioid delivery systems offering safer, more selective pain management.