Inflammation of the skin induces release and extrasynaptic spread of neuropeptides such as substance P mainly in spinal laminae I and II and causes changes in discharge properties of nociceptive neurons in spinal dorsal horn. To evaluate the role of extrasynaptic substance P we have superfused the spinal cord at recording segment with artificial cerebrospinal fluid or with substance P. A total of 102 multireceptive neurons responding to both noxious and innocuous skin stimulation were recorded in laminae I or II of lumbar spinal dorsal horn in pentobarbital anaesthetized rats. During superfusion with substance P (10 or 100pM) significant increases of background activities (from 2.2