Blockade by met-enkephalin antiserum of analgesia induced by substance P in mice.

In the tail-flick test in mice, the intraventricular administration of Substance P (10-5,000 ng/mouse) produced a naloxone-reversible analgesic effect of rapid onset and long duration. The dose-response curve was bell-shaped, the analgesic effect being smaller after the largest doses. The analgesia was blocked by concomitant intraventricular administration of the antibody against met-enkephalin but not by the antibody against beta-endorphin. In the hot plate assay, Substance P produced analgesia in mice with high sensitivity to pain, and hyperalgesia in mice with lower sensitivity to pain than normal. The analgesia was blocked by the antibody against met-enkephalin but the hyperalgesia or the scratching response were not modified by the antiserum. The results appear to indicate a dual effect, analgesic or hyperalgesic, of Substance P in mice, the former probably being mediated by release of met-enkephalin.