Analgesic effect of substance P and related hexapeptides

Substance P (SP) (90 and 180 nM/kg ip) markedly prolonged the paw-licking latency in mouse hot-plate method, but had little effect on jump-off latency. Analgesic effect of SP was slow in onset and reached its maximum about 60 min after ip administration. SP (180 nM/kg) administered 90 min before experiment increased significantly the stimulation threshold for flinch, squeak and jump response in the mouse flinch-squeak method. Naloxone (1 mg/kg sc) completely blocked the analgesic action of SP. Experiments in vitro showed no binding of SP to the opiate receptor. SP inhibited the locomotor activity; this effect was not antagonized by naloxone. Hexapeptides SP(5-11) (-2) and (pGlu₆)SP(6-11) (Z-1) also inhibited the locomotor activity in mice and reduced pain sensitivity. Both hexapeptides showed a moderate binding activity to the opiate receptor in rat striatum.