STUDIES ON THE ANTIINFLAMMATORY, IMMUNOREGULATORY, AND ANALGESIC ACTIONS OF MELATONIN

In order to develop melatonin (MT) as a potential new drug for the tre atment of diseases with inflammation, pain, and abnormal immune respon ses, the effects and mechanisms of MT on inflammation, immunoregulatio n, and nociception were studied systematically. MT (40-160 mg/kg, ip) had significant analgesic effects in the hot-plate, writhing, and tail -flick models, with a marked dose- and time-dependence. The onset of i ts analgesia about 30-60 min after ip, was slower than that of pethidi ne, but the duration was longer (about 1.5-2 h). The analgesia was als o induced by icy MT (0.25 mg/kg) injection. A lower dose of MT (10 mg/ kg) could enhance the analgesic effect of pethidine, which was blocked by naloxone (10 mg/kg). MT (100 mg/kg, ip) decreased the content of b eta-endorphin in the hypothalamus and pituitary. The analgesia of MT c ould be attenuated by pretreatment with reserpine (30 mg/kg, ip) or ph entolamine (10 mg/kg, ip). CaCl2 (230 mg/kg) could antagonize the anal gesia of MT. EGTA and verapamil had opposite effects to CaCl2. No tole rance and dependence to MT was found in mice. Further studies showed t hat MT could enhance the functions of T and B lymphocytes and macropha ges in vitro and in adjuvant arthritis, and inhibit the disturbance of immune cells. MT could inhibit the swelling of hindpaw induced by car rageenin and complete Freund's adjuvant. These factors suggest that MT possesses marked antiinflammatory, immunoregulatory, and analgesic ef fects which may be related to the system of opiate,monoamine, and Ca2 modulation. (C) 1997 Wiley-Liss, Inc.