COMPARISON OF THE TIME-COURSE OF MORPHINES ANALGESIC AND IMMUNOLOGICAL EFFECTS

Morphine, an opioid analgesic commonly prescribed and abused, produces immune-altering effects. Whether morphine's antinociceptive and immun ologic effects occur concurrently is unknown. Therefore, we investigat ed the time course of morphine's immunologic and antinociceptive effec ts. Rats were given a 15 mg/kg morphine injection (subcutaneously), an d experimental assessments were taken at 30 min, 1 h, 2 h, 6 h, 12 h, and 24 h after treatment. Immune measures included natural killer (NK) cell activity, proliferation of splenic T and B lymphocytes, and cyto kine production. Antinociception was assessed by using the tail withdr awal assay. Results show that morphine's immunomodulatory effects on N K cell activity begin within 30 min, continue for at least 12 h, and r eturn to control values by 24 h. In contrast, proliferation of splenic T and B cells and interferon-gamma production are not altered within 30 min; maximal suppression occurs at 1 h, and recovery begins within 2 h. In all immune measures, therefore, maximal suppression is present at the 1-h time point, and recovery is complete within 24 h. Morphine induces antinociception 30 min to 2 h after drug administration; reco very is complete within 6 h. These results suggest the possibility tha t different mechanisms modulate morphine's immunologic and analgesic e ffects. Implications: Acute morphine treatment in rats produces immune alterations and antinociception. Although there are slight difference s in morphine's maximal immunological and antinociceptive effects, mor phine suppresses immune status at time points concordant with its anti nociceptive effects. These effects should be considered when administe ring morphine to patients whose systems are immunocompromised.