Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo

The central terminals of small diameter primary sensory neurones associated with the transmission of noxious cutaneous stimuli are located predominantly in the superficial dorsal horn of the spinal cord 1–3 . Some of these neurones synthesize substance P (ref. 4) and transport this peptide to their central and peripheral terminals 5–7 . Substance P is released from the dorsal horn in vitro following potassium depolarization 8,9 ; from spinal cord after electrical stimulation of dorsal roots 10 and from dissociated sensory neurones grown in culture 11 . The iontophoretic application of substance P produces a long-lasting excitation of dorsal horn neurones that are also excited by noxious cutaneous stimuli 12–14 . One population of opiate receptors in the dorsal horn seems to be located on primary afferent terminals 15–16 ; the release of substance P from primary sensory neurones is inhibited by opiates in vitro 8,11 . At present, however, there is no direct evidence that substance P is released from sensory neurones, in vivo , following activation of nociceptive afferents. We report here that substance P-like immunoreactivity is released from the mammalian spinal cord, in vivo , following chemical stimulation of sensory neurones with capsaicin and by the activation of high threshold peripheral afferents. Furthermore, release of substance P evoked by high intensity stimuli is completely inhibited by intrathecal morphine.