Kyotorphin (Kyo), an endogenous neuropeptide (tyrosine-arginine), plays a role in pain regulation in the brain. This peptide administered centrally produced analgesic effects in mice, possibly through a Met-enkephalin release. The neurochemical basis of mechanisms suggests that Kyo stimulates its specific receptor, followed by Gi and phospholipase C (PLC) activations. Recently, we observed that this PLC mechanism leads to a Ca2+ influx in nerve ending particles or synaptosomes. In this report, we propose the hypothesis that inositol 1,4,5-trisphosphate (InsP3) elicits Ca2+ transport through plasmalemmal InsP3 receptor but not through intrasynaptosomal Ca2+ stores. Because neurochemically dissociated synaptosomes may not be exclusively pure but may contain various other subfractions, however, this hypothesis is required to be further confirmed through more physiological approaches.