Analgesic effect of L-arginine in patients with persistent pain.

Our previous pharmacological studies using animals indicated that a systemic administration of L-arginine induces an antinociceptive effect and an increase in the brain level of kyotorphin (L-tyrosinyl-L-arginine) which is an endogenous analgesic peptide and a methionine-enkephalin releaser in the brain. The aims of this study were to investigate the analgesic effect of L-arginine, a precursor of kyotorphin, in persistent pain. We selected 12 patients with various kinds of pain of at least 6 months duration. L-Arginine (10% solution, 300 ml (30 g)/patient) was administered by intravenous drip at a rate of 5 ml (0.5 g)/min during a period of 60-70 min. Pain was assessed by the patient using a 10-cm visual analogue scale (VAS), before and after the L-arginine infusion. L-Arginine treatment resulted in slight analgesia at 10-15 min after the onset of infusion and in marked analgesia at 30-40 min after that. This effect lasted for 6-24 h. L-Arginine-induced analgesia was dose-dependent and blocked by intravenous injection of naloxone. In each case, the L-arginine-induced analgesia was statistically significant as compared with the saline-induced effect. Side effects of L-arginine were a slight decrease in mean blood pressure (10-15 mm Hg), and dryness of the month. A suppressive role of a functional link between the L-arginine-kyotorphin system and the enkephalin system of the brain in persistent pain is suggested.